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Retriever2200
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Time to think: Selecting patients who may benefit from synchronous resection of primary pancreatic cancer and liver metastases.
Pancreatic cancer remains a lethal disease and is associated with poor prognosis, particularly for patients with distant metastasis at diagnosis. Recently, Oweira reported a retrospective study that included 13233 metastatic pancreatic cancer patients from the Surveillance, Epidemiology and End Results database. They demonstrated that pancreatic cancer patients with isolated liver metastases had worse outcomes than patients with isolated lung metastases or distant nodal metastases. At present, the standard treatment for metastatic pancreatic cancer is chemotherapy. However, improvement in the safety of pancreatic surgery has led to the consideration of more aggressive surgical approaches. Schneitler reported two cases of hepatic metastatic pancreatic cancer in which negative margin (R0) resection and long survival were achieved after effective preoperative chemotherapy. In general, these two studies indicate that although pancreatic cancer patients with liver metastasis have a poor prognosis, surgical approaches may prolong survival for a few of these patients. A strategy to select hepatic metastatic pancreatic cancer patients who may benefit from surgical intervention is urgently needed.
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No pos
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No neg
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Retriever2201
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[Performance improvement project for the introduction of safety devices: interdisciplinary approach and participation of professionals].
OBJECTIVE
Develop a performance improvement project to introduce safety needle tube holder for venous blood collection after evaluation of the professionals.
METHODS
Reach: Costa Ponent Primary Care Direction and the Hospital Viladecans Hospital from Institute Català de la Salut.
METHOD
Create interdisciplinary group. Design in two phases. First, material selection and assessment of safety devices. Second, implementation and evaluation of the proposed performance improvements. The material was selected using standardized criteria on safety devices, suitability to clinical practice and technical compatibility The assessment was qualitative questionnaire by adapting the Centers for Disease Control and Prevention.
RESULT
We evaluated three types of needles, two of them were evaluated by 54 primary care professionals and one for 12 professionals from the hospital. Good acceptance regarding their interaction with technology and patient safety. It was considered effective safety device. The overall rating was satisfactory. Underutilized the material by hospital professionals. There were no differences regarding sex, the hand size, experience, training you received, and type of needle. It prepared a proposal to come in progressively safety needle tube holder in primary care. The evaluation performed in the hospital it was considered insufficient.
CONCLUSIONS
Interdisciplinary participation is essential to implement measures to safe care. The safety needle evaluated were effective with respect to security professionals and the patient. The involvement of different levels of the organization have developed a proposal for performance improvement adapted to the needs of our environment.
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No pos
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No neg
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Retriever2202
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Trends of genetic screening in patients with pheochromocytoma and paraganglioma: 15-year experience in a high-volume tertiary referral center.
BACKGROUND AND OBJECTIVES
Genetic testing for pheochromocytoma and paraganglioma allows for early detection of hereditary syndromes and enables close follow-up of high-risk patient. We investigated the trends in genetic testing among patients at a high-volume referral center and evaluated the prevalence of pheochromocytomas and paragangliomas.
METHODS
We reviewed the charts of 129 patients who underwent adrenalectomy for pheochromocytoma and paraganglioma between January 2000 and July 2015. To evaluate for trends in genetic testing, patients were divided by year of diagnosis: 2000-2005 (group 1, n = 35), 2006-2010 (group 2, n = 44), and 2011-2015 (group 3, n = 50).
RESULTS
Among 129 patients the mean age was 47 years and 56% were women. Groups 2 and 3 were more frequently referred for genetic consultation than group 1, 73%, and 94% versus 26% (P < 0.001). A total of 67% followed up on the referral. The prevalence of genetic mutation was 50% (21/42 tested). The percentage with a genetic syndrome was 23%, 28%, and 22% respectively for groups 1, 2, and 3.
CONCLUSIONS
Referral for genetic counseling significantly increased in the past 15 years. However, only two-thirds of patients followed up with genetic counselors and, therefore, clinicians can do more to improve the adherence rate for genetic counseling.
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No pos
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No neg
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Retriever2203
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Elucidating the Functional Role of Human ABHD16B Lipase in Regulating Triacylglycerol Mobilization and Membrane Lipid Synthesis in Saccharomyces cerevisiae.
Lipids are essential biological macromolecules that play a pivotal role in various physiological processes and cellular homeostasis. ABHD16B, a member of the α/β-hydrolase domain (ABHD) superfamily protein, has emerged as a potential key regulator in lipid metabolism. However, the precise role of human ABHD16B in lipid metabolism remains unclear. In this study, we reported the overexpression of ABHD16B in Saccharomyces cerevisiae to determine its physiological relevance in lipid metabolism. Through in vivo [14C]acetate labeling experiments, we observed that overexpression of ABHD16B causes a decrease in cellular triacylglycerol (TAG) levels and a concurrent increase in phospholipid synthesis in wild-type cells. Mass spectrophotometry (LC-MS/MS) analysis further corroborated these findings, showing a significant decrease in TAGs with a carbon chain length of 48 and an increase in major phospholipid species, specifically 34:2, upon overexpression of ABHD16B. Confocal microscopy analysis revealed a reduction in the number of lipid droplets in strains overexpressing ABHD16B, consistent with the observed decrease in neutral lipids. Additionally, qRT-PCR analysis indicated a high phospholipid synthetic activity of ABHD16B and a potential decrease in TAG levels in wild-type yeast, possibly due to upregulation of endogenous TAG hydrolytic enzymes, as confirmed using 3tglsΔ mutant strain. Furthermore, GC-MS analysis revealed significant modifications in fatty acid composition upon ABHD16B overexpression. Collectively, our results underscore the influence of ABHD16B overexpression on TAG levels, phospholipid synthesis, lipid droplet dynamics, and fatty acid composition. These findings reveal a complex interplay between TAG hydrolysis and phospholipid synthesis, highlighting the critical involvement of ABHD16B in lipid homeostasis and providing further insights into its regulatory function in cellular lipid metabolism.
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No pos
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Retriever2204
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Meiofaunal community analysis by high-throughput sequencing: comparison of extraction, quality filtering, and clustering methods.
Using molecular tools to examine community composition of meiofauna, animals 45μm to 1mm in size living between sediment grains in aquatic environments, is relatively new in comparison to bacterial and archaeal microbial studies. Although high-throughput molecular approaches are starting to be applied to these ccommunities, effectiveness of different approaches for nucleic acid extraction from meiofauna is poorly known and bioinformatic pipelines vary between studies. Given this situation, there is a need for protocols to be developed that promote consistency in sample collection and processing, sequence quality filtering, and Operational Taxonomic Unit (OTU) clustering methods. Herein, we assess different approaches used for DNA extraction (DNA extracted directly from sediment versus elutriated material retained on a 45μm sieve) as well as how different quality filtering methods of sequences and OTU clustering algorithms impact genetic assessment of meiofauna community composition. DNA extracted directly from sediment resulted in higher presence of non-metazoan eukaryotic taxa; in contrast, an elutriation (resuspension with decanting) approach increased meiofauna abundance and enriched metazoan OTUs. In regards to bioinformatics analyses, the number of overall OTUs varied by clustering algorithm, primarily due to the applied method of sequence quality filtering. However, alpha and beta diversity analyses showed similar trends regardless of bioinformatics pipeline utilized. Based on our results, we recommend studies of meiofauna communities first elutriate samples prior to DNA extraction and include multiple biological replicates to account for variation in community-level composition. The quality filtering method should be carefully considered as this step accounted for large discrepancy in the number of OTUs inferred.
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No pos
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Retriever2205
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Sila-spirocyclization involving unstrained C(sp3)-Si bond cleavage.
C - Si Bond cleavage is one of the key elemental steps for a wide variety of silicon-based transformations. However, the cleavage of unstrained Si-C(sp3) bonds catalyzed by transition metal are still in their infancy. They generally involve the insertion of a M - C(sp2) species into the C - Si bond and consequent intramolecular C(sp2)‒Si coupling to exclusively produce siloles. Here we report the Pd-catalyzed sila-spirocyclization, in which the Si-C(sp3) bond is activated by the insertion of a M - C(sp3) species and followed by the formation of a new C(sp3)‒Si bond, allowing the construction of diverse spirosilacycles. This reactivity mode, which is strongly supported by DFT calculations may open an avenue for the Si-C(sp3) bond cleavage and silacycle synthesis.
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No pos
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Retriever2206
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[Atypical lipoma, floret-like pleomorphic variant. A lipomatous lesion simulating a liposarcoma].
A case of submucous lump of the majus labium of a 56 year old female has reported. This is a composite lesion which shows a loose connectival texture and a high cellularity with spindle cells, multivacuolated cells of irregular shape and hyperchromatic nuclei; moreover, there are characteristic multinucleated floret-like cells. This is a particular variant of Atypical Lipoma defined as Pleomorphic Lipoma by Enzinger. Despite this ominous cellularity, the lesion is perfectly benign. The small size and the superficial site are the majors elements of good prognosis. In retroperitoneal localization lesions with similar histologic presentation and of major size show more severe prognosis and are classified as Low Grade Well Differentiated Liposarcoma.
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No pos
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Retriever2207
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Vaccination with peptides from MHC class II beta chain hypervariable region causes allele-specific suppression of EAE.
In our earlier studies we showed that successful immunotherapy of EAE in SJL/J mice can be achieved either by the use of antibodies to MHC class II antigens or by vaccination with synthetic peptide analogs of the beta chain of MHC class II molecules. We proposed that inhibition of EAE following vaccination with synthetic peptides derived from the beta chain of mouse I-A, was in part due to the generation of auto-anti-MHC class II antibodies that interfered with T cell sensitization. In our present study we show that suppression of EAE following vaccination results in poor sensitization of MBP reactive T cells, and that the lack of immune response is allele-specific. In F1(SJL(I-AS) x Balb/cI-Ad) mice, in which susceptibility to EAE is linked closely to the I-AS allele, vaccination with peptides from beta chain of I-AS results in inhibition of proliferative response to MBP and prevents the development of EAE. Vaccination with peptide from the beta chain of I-Ad did not affect either the development of immune response to MBP or the induction of EAE, indicating allele-specific suppression. Since global immunosuppression is not induced by vaccination with I-A peptides, we propose that this strategy can be extended to human autoimmune diseases wherein a clear association between certain MHC class II alleles and autoimmune disease is evident.
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No pos
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Retriever2208
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[Investigation of nitrogen, phosphorus and microbial contamination in Laolongdong underground river system of Chongqing].
With urbanization, groundwater in China has been widely polluted. Karst groundwater is important in southwest China, and would be difficult to recover once contaminated. NO3(-), PO4(3), NH4(+), total coliform, total E. coli and fecal coliform were chosen as indexes in the study of groundwater of Laolongdong Underground River System in Nanshan Mountain, Chongqing. After a few years of survey, the results showed that NO3(-), NH4(+) and PO4(3-) concentrations in the water were all above the nature value, especially NH4(+) and PO4(3-). The NO3(-) concentration of Guihuawan spring ranged from 19.78-68.55 mg x L(-1), in some months, above the recommended water quality guideline (50 mg x L(-1)) according to Standards for Drinking Water Quality set by World Health Organization. NH4(+) and PO4(3-) concentrations in Laolongdong underground river varied from 2.71-12.92 mg x L(-1) and 0.16-11.22 mg x L(-1). The NO3(-) concentration in Laolongdong underground river was lower than in karst spring; however, the concentrations of NH4(+) and PO4(3-) were higher than in the spring. It seemed that the NO3(-) concentration tended to decrease from 2008 to 2013 in the underground river caused by urbanization, reduction of farmland and reducing environment. However, waste water with a high PO4(3-) concentration led to an increasing trend in the PO4(3-) concentration in underground river. Microbial contamination was extremely serious, and even far exceeded class V of water quality standards of China. For example, the concentration of fecal coliform in the groundwater ranged from 3.4 x 10(4)-3.68 x 10(4) CFU x mL(-1). Because of the special hydrogeological structure, karst depressions, skylights and sinkholes can lead pollutants easily to the underground water. Agriculture activity, sewage from towns, enterprises and residential areas were the major sources of nitrogen, phosphorus and microbial contamination.
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No pos
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Retriever2209
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Effect of removable orthodontic appliance on taste and flavor perception--a clinical study.
Removable orthodontic appliances are known to be the cause of various complaints related to oral handling of food and beverages, phonation and vocalization. To evaluate the complaint regarding appliance and its effect on taste and flavor perception, 100 volunteers were selected for the study. Two groups (I and II) of 50 children each were divided as study and control groups between the age group of 8- 13 years. Selected volunteers were given taste and flavor stimuli and were asked to score as per their perception in different testing sessions. The overall results revealed that volunteers from both study and control groups, irrespective of the use of removable orthodontic appliances showed marked variation in the estimation of the taste and flavor stimuli in different testing sessions. However, the results obtained were statistically not significant.
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No pos
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No neg
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Retriever2210
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Dl-3-n-butylphthalide, a natural antioxidant, protects dopamine neurons in rotenone models for Parkinson's disease.
In the absence of a cure for Parkinson's disease, development of preventive medications for this devastating disease is particularly encouraged. Dl-3-n-butylphthalide (NBP), an established natural antioxidant for clinical stroke treatment in China, can reportedly reduce beta-amyloid-induced neuronal toxicity in cultured neuronal cells, and attenuate neurodegenerative changes in aged rats. However, whether or not NBP confers neuroprotection in parkinsonian models is still unknown. In this study, we investigated the effects of NBP in rotenone models for Parkinson's diseases. In a cellular model, pretreatment with NBP enhanced cell viability by decreasing nuclear fragmentation, retaining mitochondrial membrane potential, and preventing reactive oxygen species (ROS) from generation. In a rodent model, 2-week treatment with NBP was able to ameliorate apomorphine-evoked rotations by 48% and rescue dopaminergic (DA) neurons by 30% and striatal DA terminal by 49%. Furthermore, NBP upregulated the vesicular monoamine transporter 2 gene expression in vitro and in vivo. Together, NBP protects DA neurons likely by reducing oxidative stress, offering an alternative neuroprotective medication for Parkinson's disease.
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No pos
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No neg
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Retriever2211
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JCAHO solutions. Ins and outs of advance directives.
Nurses' responsibilities surrounding patients' advance directives can vary by setting.
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No pos
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No neg
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Retriever2212
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Histone variant H2A.Z and RNA polymerase II transcription elongation.
Nucleosomes containing histone variant H2A.Z (Htz1) serve to poise quiescent genes for activation and transcriptional initiation. However, little is known about their role in transcription elongation. Here we show that dominant mutations in the elongation genes SPT5 and SPT16 suppress the hypersensitivity of htz1Δ strains to drugs that inhibit elongation, indicating that Htz1 functions at the level of transcription elongation. Direct kinetic measurements of RNA polymerase II (Pol II) movement across the 9.5-kb GAL10p-VPS13 gene revealed that the elongation rate of polymerase is 24% slower in the absence of Htz1. We provide evidence for two nonexclusive mechanisms. First, we observed that both the phospho-Ser2 levels in the elongating isoform of Pol II and the loading of Spt5 and Elongator over the GAL1 open reading frame (ORF) depend on Htz1. Second, in the absence of Htz1, the density of nucleosome occupancy is increased over the GAL10p-VPS13 ORF and the chromatin is refractory to remodeling during active transcription. These results establish a mechanistic role for Htz1 in transcription elongation and suggest that Htz1-containing nucleosomes facilitate Pol II passage by affecting the correct assembly and modification status of Pol II elongation complexes and by favoring efficient nucleosome remodeling over the gene.
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No pos
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Retriever2213
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Effects of high serum uric acid levels on oxidative stress levels and semen parameters in male infertile patients.
This study is to investigate the effect of high serum uric acid (UA) level on oxidative stress and semen quality of male infertility patients.A cohort of 654 male individuals aged between 20 and 45 years old were included in this study, and their semen and venous blood samples were collected. The serum UA, blood glucose, blood lipids, and hormone levels were determined by chemiluminescence method. The changes in inflammatory factors, oxidative stress, adipokines, and biochemical indices in seminal plasma were determined by ELISA. Organic acids in seminal plasma were detected with reversed-phase ultra high performance liquid chromatography.Compared with the control group, the amount of semen and the total number of sperm in the hyperuricemia group significantly reduced (P < .05). Semen volume decreased with the increase of serum UA level, and the total number of sperm also decreased. The level of luteinizing hormone increased and the level of testosterone decreased in the hyperuricemia group. The concentration of superoxide dismutase decreased and the concentration of endothelin increased in the hyperuricemia group (P < .05). The concentration of seminal plasma α-glucosidase and alkaline phosphatase in the hyperuricemia group decreased significantly (P < .05). Compared with the control group, the contents of ascorbic acid, tartaric acid, lactic acid, and UA in the seminal plasma were significantly reduced in the hyperuricemia group (P < .05).Blood UA level may become a new risk predictor of semen quality in infertile men.
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No pos
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No neg
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Retriever2214
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Genetic drift in an outbred stock of mice.
Survey in protein polymorphism in the nucleus colony of the Him: OF 1-mouse outbred stock showed that 8 of 53 loci were variable in the stock. Allele frequencies of these eight loci (Idh-1, Mup-1, Pgm-1; Ldr-1, Gpi-1s, Hbb, Mod-1, Ce-2) changed between generations investigated. The average percentage of heterozygote animals for these loci decreased with generation. These suggested that genetic drift occurred in the breeding stock. Examination in the breeding record sheets showed that genetic drift was caused by mistakes in mating probably due to repeated personnel changes and insufficient training of the animal technicians. Mice had not been paired according to the schemes prescribed, pairing among relatives and reduction of the number of litters used for mating occurred. The increase in homozygosity showed only little effect on breeding parameters: The interval between pairing and first and second litter increased significantly.
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No pos
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No neg
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Retriever2215
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Involvement of NpdA, a Putative 2-Nitropropane Dioxygenase, in the T3SS Expression and Full Virulence in Ralstonia solanacearum OE1-1.
Previously, we isolated several genes that potentially affected the expression of type III secretion system (T3SS) in Ralstonia solanacearum OE1-1. Here, we focused on the rsp0316, which encodes a putative 2-nitropropane dioxygenase (hereafter designated NpdA). The deletion of npdA substantially reduced the T3SS expression and virulence in OE1-1, and the complementation with functional NpdA could completely restore its reduced T3SS expression and virulence to that of wild type. The NpdA was highly conserved among diverse R. solanacearum species and the NpdA-dependent expression of T3SS was not specific to OE1-1 strain, but not the virulence. The NpdA was important for the T3SS expression in planta, while it was not required for the bacterial growth in planta. Moreover, the NpdA was not required for the elicitation of hypersensitive response (HR) of R. solanacearum strains in tobacco leaves. The T3SS in R. solanacearum is directly controlled by the AraC-type transcriptional regulator HrpB and regulated by a complex regulation network. The NpdA affected the T3SS expression mediated with HrpB but through some novel pathway. All these results from genetic studies demonstrate that NpdA is a novel factor for the T3SS expression in diverse R. solanacearum species in medium, but specifically for the T3SS expression in strain OE1-1 in planta. And the NpdA-dependent expression of T3SS in planta plays an important role in pathogenicity of R. solanacearum OE1-1 in host plants.
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No pos
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No neg
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Retriever2216
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Deep learning based atmospheric turbulence compensation for orbital angular momentum beam distortion and communication.
Atmospheric transmission distortion is one of the main challenges hampering the practical application of a vortex beam (VB) which carries orbital angular momentum (OAM). In this work, we propose and investigate a deep learning based atmospheric turbulence compensation method for correcting the distorted VB and improving the performance of OAM multiplexing communication. A deep convolutional neural network (CNN) model, which can automatically learn the mapping relationship of the intensity distributions of input and the turbulent phase, is well designed. After trained with loads of studying samples, the CNN model possesses a good generalization ability in quickly and accurately predicting equivalent turbulent phase screen, including the untrained turbulent phase screens. The results show that through correction, the mode purity of the distorted VB improves from 39.52% to 98.34% under the turbulence intensity of Cn2 = 1 × 10-13. Constructing an OAM multiplexing communication link, the bit-error-rate (BER) of the transmitted signals in each OAM channel is reduced by almost two orders of magnitude under moderate-strong turbulence, and the demodulated constellation diagram also converges well after compensated by the CNN model.
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No pos
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No neg
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Retriever2217
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Measurement error and its impact on the estimated relationship between dust lead and children's blood lead: Members of the Rochester Lead-in-Dust Study Group.
OBJECTIVE
Lead-contaminated house dust is a major contributor to lead intake among urban children, but the reliabilities of various dust lead measurement methods and their impact on the estimated correlations between dust lead and children's blood lead levels are unknown.
METHODS
Repeated field measurements of lead-contaminated dust from children's homes were taken from 16 housing units using five dust lead measurement methods. Estimates of measurement error were used to obtain reliability ratios for the dust lead measurements, which were then used to correct estimated correlations between lead-contaminated dust and children's blood lead.
RESULTS
Reliability varied over methods and surface types (from 0.0 to 0.8), but wipe loading and the BRM vacuum loading methods generally had greater reliability. Technician effects, inadvertent field exposure to lead, contamination of collection equipment, and laboratory instrument error were found to contribute little to total measurement error. Corrected correlations between blood lead and wipe loading measurements were 7 to 104% higher than uncorrected correlations. The multiple R2 and partial R2 for a wipe composite measurement in a multivariate regression model increased from 0.43 to 0.64 and from 0.053 to 0.26, respectively, after correction for measurement error bias.
CONCLUSIONS
Variation in lead deposition within small areas and variations in collection inherent to the devices are major contributors to measurement error. Measurement error causes dramatic underestimation of correlation between lead-contaminated house dust and children's blood lead.
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No pos
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No neg
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Retriever2218
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A new method for identification of protein (sub)families in a set of proteins based on hydropathy distribution in proteins.
Structural similarity among proteins is reflected in the distribution of hydropathicity along the amino acids in the protein sequence. Similarities in the hydropathy distributions are obvious for homologous proteins within a protein family. They also were observed for proteins with related structures, even when sequence similarities were undetectable. Here we present a novel method that employs the hydropathy distribution in proteins for identification of (sub)families in a set of (homologous) proteins. We represent proteins as points in a generalized hydropathy space, represented by vectors of specifically defined features. The features are derived from hydropathy of the individual amino acids. Projection of this space onto principal axes reveals groups of proteins with related hydropathy distributions. The groups identified correspond well to families of structurally and functionally related proteins. We found that this method accurately identifies protein families in a set of proteins, or subfamilies in a set of homologous proteins. Our results show that protein families can be identified by the analysis of hydropathy distribution, without the need for sequence alignment.
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No pos
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No neg
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Retriever2219
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Modulation of spontaneous hippocampal synaptic events with 5-hydroxyindole, 4OH-GTS-21, and rAAV-mediated alpha7 nicotinic receptor gene transfer.
One approach to treatment of negative cognitive effects associated with Alzheimer's disease and schizophrenia may involve activation of neuronal alpha7 nicotinic acetylcholine receptors (nAChRs). We used the alpha7-selective partial agonist 3-(4-hydroxy, 2-methoxy-benzylidene)anabaseine (4OH-GTS-21), the alpha7 modulator 5-hydroxyindole (5-HI), and recombinant adeno-associated virus (rAAV)-mediated alpha7 gene transfer in order to test the hypothesis whether combining these strategies would significantly increase indirect measures of alpha7 nAChR function, including measures of spontaneous synaptic events in CA1 pyramidal cells. 5-HI (1 mM), and 5-HI (1 mM)+4OH-GTS-21 (5 microM) increased the frequency of APV- and NBQX-sensitive currents, while 5-HI+4OH-GTS-21 increased the frequency and amplitude of bicuculline-sensitive currents. Effects on EPSCs were blocked with tetrodotoxin (TTX) (1 microM), but not by methyllycaconitine (MLA) (50 nM). Neither TTX nor MLA reduced the potentiation of IPSC frequencies. However, TTX blocked, and in some cases MLA reduced, the potentiation of IPSC amplitudes. These data suggest that effects of 5-HI+4OH-GTS-21 on EPSC frequency were associated with action potential-dependent transmitter release produced by 5HI, and that potentiation of IPSC amplitudes resulted at least in part, from activation of alpha7 nAChRs. Finally, rAAV-mediated alpha7 gene transfer did not alter the magnitude of effects produced by 5-HI or 5-HI+4OH-GTS-21. Thus, although we previously showed that direct measures of alpha7 nAChR function were enhanced by alpha7 gene transfer, indirect measures of alpha7 nAChRs function were not significantly enhanced by combining alpha7 gene transfer with either agonist activation or positive allosteric modulation of alpha7 nAChRs.
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No pos
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No neg
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Retriever2220
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Understanding radiation response and cell cycle variation in brain tumour cells using Raman spectroscopy.
Radiation therapy is currently utilised in the treatment of approximately 50% of cancer patients. A move towards patient tailored radiation therapy would help to improve the treatment outcome for patients as the inter-patient and intra-patient heterogeneity of cancer leads to large differences in treatment responses. In radiation therapy, a typical treatment outcome is cell cycle arrest which leads to cell cycle synchronisation. As treatment is typically given over multiple fractions it is important to understand how variation in the cell cycle can affect treatment response. Raman spectroscopy has previously been assessed as a method for monitoring radiation response in cancer cells and has shown promise in detecting the subtle biochemical changes following radiation exposure. This study evaluated Raman spectroscopy as a potential tool for monitoring cellular response to radiation in synchronised versus unsynchronised UVW human glioma cells in vitro. Specifically, it was hypothesised that the UVW cells would demonstrate a greater radiation resistance if the cell cycle phase of the cells was synchronised to the G1/S boundary prior to radiation exposure. Here we evaluated whether Raman spectroscopy, combined with cell cycle analysis and DNA damage and repair analysis (γ-H2AX assay), could discriminate the subtle cellular changes associated with radiation response. Raman spectroscopy combined with principal component analysis (PCA) was able to show the changes in radiation response over 24 hours following radiation exposure. Spectral changes were assigned to variations in protein, specifically changes in protein signals from amides as well as changes in lipid expression. A different response was observed between cells synchronised in the cell cycle and unsynchronised cells. After 24 hours following irradiation, the unsynchronised cells showed greater spectral changes compared to the synchronised cells demonstrating that the cell cycle plays an important role in the radiation resistance or sensitivity of the UVW cells, and that radiation resistance could be induced by controlling the cell cycle. One of the main aims of cancer treatment is to stop the proliferation of cells by controlling or halting progression through the cell cycle, thereby highlighting the importance of controlling the cell cycle when studying the effects of cancer treatments such as radiation therapy. Raman spectroscopy has been shown to be a useful tool for evaluating the changes in radiation response when the cell cycle phase is controlled and therefore highlighting its potential for assessing radiation response and resistance.
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No pos
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No neg
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Retriever2221
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Comparative anaerobic digestion of sewage sludge at different temperatures with and without heat pre-treatment.
Anaerobic digestion of sewage sludge is generally conducted under mesophilic (around 35 °C) or thermophilic (around 55 °C) conditions, whereas it is conducted at lower temperatures in some wastewater treatment plants without heating. In this study, we compared the anaerobic digestion of sewage sludge at 15, 25, 30, 35, 45, and 55 °C following hyperthermophilic pre-treatment at 80 °C for 24 h. Laboratory-scale reactors were operated continuously for more than 1000 days, and batch experiments were performed to evaluate the reaction kinetics. Biogas production rates at 15 °C with and without pre-treatment divided by that at 35 °C without pre-treatment were 0.73 and 0.78, respectively. The dewaterability of the digested sludge was evaluated by the capillary suction time (CST). The CST was approximately 50 s at 15 °C with and without pre-treatment and was slower than the CST at 35 °C. Compared to the shear rate, viscosity was higher at lower temperatures; however, it decreased with pre-treatment, which reduced the energy required for mixing in the reactors. Pre-treatment eliminated Escherichia coli from the sludge; however, E. coli (approximately 105 colony forming unit/g-total solids) was detected after digestion at temperatures ≤30 °C. Pre-treatment was also useful to replace a part of heat treatment required for digested sludge before it was used as fertilizer. Gene sequencing analyses indicated the effects of pre-treatment and digestion temperature on the microbial community in the digested sludge. Co-generation of biogas is useful to obtain both electricity and heat; however, heat from co-generation is sometimes limited. To maximize electricity recovery, the use of low temperature digesters has the potential to reduce fuel costs. The results indicate that anaerobic digestion at low temperatures with or without heat pre-treatment can be an efficient and cost-effective method of treating sewage sludge.
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No pos
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No neg
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Retriever2222
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The developmental relation between cognitive stage and the comprehension of speaker uncertainty.
3 hypotheses were tested concerning the developmental relation between children's concepts of physical uncertainty and their comprehension of a speaker's uncertainty. 2 cognitive tasks of physical uncertainty were used to assign 56 subjects (aged 5-4 to 17-11) to 1 of 3 cognitive stages. 2 tests for comprehension of speaker uncertainty were administered to all participants. The results indicated that cognitive stage was related to (a) comprehension that a speaker could be uncertain, (b) comprehension that uncertainty could be expressed in different degrees or magnitudes, and (c) the internal consistency of judgments made about the relative degree of uncertainty conveyed by an utterance. These findings are interpreted as evidence for the position that development of cognitive stages is structurally related to comprehension of speech act uncertainty.
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No pos
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No neg
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Retriever2223
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Effect of cycloheximide on temperature regulation in rats.
The effect of cycloheximide, an inhibitor of protein synthesis, on temperature regulation in afebrile rats was studied to determine whether its reported antipyretic effect might be attributable to a non-specific antimetabolic effect. Within 60 min after administration of cycloheximide (5 mg/kg IP) to female rats at ambient temperatures of 34, 25 and 15 degrees C, a significant decrease in colonic temperature was observed as compared with control rats administered saline IP. Measurements of rate of oxygen consumption showed that cycloheximide (5 mg/kg IP) significantly depressed the ability of rats to increase their heat production during a cold stress (15 degrees C). In the cold the rate of oxygen consumption increased 8.7 +/- 0.8 ml/min/kg0.75 in the control rats but only 1.8 +/- 0.9 ml/min/kg0.75 in the cycloheximide-treated rats. Since the thermoregulatory changes accompanying cold stress are similar to those observed during the genesis of fever, these data suggest that cycloheximide may have a general depressant effect on heat production rather than a specific antipyretic effect.
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No pos
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No neg
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Retriever2224
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Comparison of non-ideal solution theories for multi-solute solutions in cryobiology and tabulation of required coefficients.
Thermodynamic solution theories allow the prediction of chemical potentials in solutions of known composition. In cryobiology, such models are a critical component of many mathematical models that are used to simulate the biophysical processes occurring in cells and tissues during cryopreservation. A number of solution theories, both thermodynamically ideal and non-ideal, have been proposed for use with cryobiological solutions. In this work, we have evaluated two non-ideal solution theories for predicting water chemical potential (i.e. osmolality) in multi-solute solutions relevant to cryobiology: the Elliott et al. form of the multi-solute osmotic virial equation, and the Kleinhans and Mazur freezing point summation model. These two solution theories require fitting to only single-solute data, although they can make predictions in multi-solute solutions. The predictions of these non-ideal solution theories were compared to predictions made using ideal dilute assumptions and to available literature multi-solute experimental osmometric data. A single, consistent set of literature single-solute solution data was used to fit for the required solute-specific coefficients for each of the non-ideal models. Our results indicate that the two non-ideal solution theories have similar overall performance, and both give more accurate predictions than ideal models. These results can be used to select between the non-ideal models for a specific multi-solute solution, and the updated coefficients provided in this work can be used to make the desired predictions.
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No pos
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No neg
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Retriever2225
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The effects of KIR2DL4 stimulated NK-92 cells on the apoptotic pathways of HER2 + /HER-breast cancer cells.
Natural killer (NK) cells are immune cells that have attracted significant attention due to their cytotoxic properties. They are believed to be highly effective in cancer therapy. In this study, anti-KIR2DL4 (Killer cell Immunoglobulin like Receptor, 2 Ig Domains and Long cytoplasmic tail 4) was used to stimulate the NK-92 activator receptor to increase their cytotoxicity on breast cancer cell lines. Unstimulated and stimulated NK-92 cells (sNK-92) were cocultured with breast cancer (MCF-7 and SK-BR-3) and normal breast (MCF-12A) cell lines at 1:1, 1:5, and 1:10 (Target:Effector) ratios. The most effective cell cytotoxicity ratio (1:10) was used in the immunostaining and western blot assays to evaluate apoptosis pathway proteins. The sNK-92 cells showed higher cytotoxic activity on breast cancer cells than NK-92 cells. sNK-92 cells had a selective significant cytotoxicity effect on MCF-7 and SK-BR-3 cells but not MCF-12A cells. While sNK-92 cells were effective at all cell concentrations, they were most effective at a 1:10 ratio. Immunostaining and western blots showed significantly higher BAX, caspase 3, and caspase 9 protein levels in all breast cancer cell groups cocultured with sNK-92 than with NK-92 cells. NK-92 cells stimulated with KIR2DL4 showed elevated cytotoxic activity. The cytotoxic activity of sNK-92 cells on breast cancer cells is via apoptosis pathways. However, their effect on normal breast cells is limited. While the obtained data contains only basic information, additional clinical studies are needed to provide a basis for a new treatment model.
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No pos
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No neg
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Retriever2226
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Clinical clerkships: students can structure their own learning.
In clinical clerkships, student learning is often unstructured and diverse. Even when curriculum objectives are explicit, they are seldom used by students to guide their learning. Student-determined learning objectives may help students to structure their learning. This study aimed to assess whether students can use this method to meet widely differing learning needs within the general practice clerkship and considered the relationship of student objectives to overall curriculum objectives. Students allocated a 5-week clerkship in general practice from April 2000 to April 2001 were required to set and meet personal learning objectives within a supportive learning environment. They recorded the strategies they used, how well objectives were met and which curriculum objectives they met. Objectives were categorised using a hierarchical system. A total of 143 (85%) students recorded 1549 objectives. Four categories accounted for 1092 (70%) of objectives: Consultation Skills; Study of Diseases; Practical Procedures, and Therapeutics. Otherwise the range of objectives set was wide, encompassing all curriculum objectives. A total of 1043 objectives were rated as satisfactorily or highly satisfactorily met and 185 (12%) were not met at all. Strategies that students used to meet objectives included clinical experience with doctors but also with practice-based nurses. Students were able to use student-determined learning objectives to meet a diverse range of learning needs within the general practice clerkship. The objectives set reflected the breadth of curriculum objectives. This method allows students to address gaps in their knowledge in a clerkship where teaching is largely based on opportunistic contact.
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No pos
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No neg
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Retriever2227
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Effect of increased ppGpp concentration on DNA replication of different replicons in Escherichia coli.
The plasmids harbouring the relA gene under an inducible promoter allowed us to increase the guanosine 5'-diphosphate-3'-diphosphate (ppGpp) concentration in Escherichia coli cells without any starvation and thus, to directly investigate the effect of ppGpp on DNA replication. We studied all types of replicons which were investigated previously in amino acid-starved bacteria and found that ColE1, oriC, lambda plasmid and pSC101 but not RK2 replicons are sensitive to high ppGpp level. To our knowledge, this paper presents the first direct evidence that replication of most, but not all, replicons is dependent on ppGpp concentration and thus, is under stringent control.
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No pos
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No neg
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Retriever2228
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Laparoscopic radical prostatectomy: the value of intraoperative frozen sections.
OBJECTIVE
To examine the clinical and pathological value of intraoperative frozen section (IFS) in patients undergoing laparoscopic radical prostatectomy (L-RPE) for clinically localized prostate cancer.
METHODS
The study includes 198 consecutive cases of L-RPE. After removal of the prostate, a 2-3mm circumferential specimen was obtained from the apical and bladder neck soft-tissue margin and submitted for IFS examination. In cases suspicious for capsular incision (n=57), IFS were taken from the neurovascular bundle/lateral pedicle.
RESULTS
The IFS diagnosis from the apical, bladder neck, and neurovascular bundle/lateral pedicle soft-tissue margins was adenocarcinoma in 12 (6%), 1 (0.5%), and 2 (1%) cases, respectively. Patient age, clinical stage, and mean specimen weight were not associated with cancer at the apical IFS. The accuracy, sensitivity, specificity, positive and negative predictive value of the apical IFS to predict cancer in the permanent section of the apical soft-tissue margin was 96%, 70%, 97%, 58%, and 98%, respectively. All the patients (n=15) with cancer at IFS had wide resections of additional tissue in the area of positive soft-tissue margin and all had no cancer in the additional resected tissue. Especially at the apex, IFS decreases the overall PSM status on surgical specimen by 5.1% (apical PSM from 8.6% to 3.5%).
CONCLUSION
Because of the low predictive value of IFS of bladder neck and neurovascular bundle/lateral pedicle their use is not recommended. IFS of the apex should be performed to reduce the PSM rate.
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No pos
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No neg
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Retriever2229
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TRH test as an index of suppression compared with the thyroid radioiodine uptake in euthyroid goitrous patients treated with thyroxine.
To determine an index of adequate suppression of pituitary TSH secretion in euthyroid goitrous patients treated with sodium levothyroxine (T4), TSH responses to 500 micrograms TRH given iv were compared with thyroid 24-h radioiodine uptakes during therapy with T4 in 12 euthyroid goitrous patients. The patients received sequentially 100, 150, 200, 250, and 300 micrograms T4 with the doses increased at 4-6 week intervals. The mean dose of T4 that reduced the peak TSH response to TSH to the lower limit of normal (TSH = 5 microU/ml) was 130 micrograms; the mean T4 dose that suppressed the TSH response to one-half the lower limit of normal (TSH = 2.5 microU/ml) was 165 micrograms. The mean T4 dose that nearly obliterated the TSH response was 200 micrograms; this degree of suppression occurred with doses of 100-300 micrograms T4 in individual patients. Suppression of thyroid uptake correlated closely with suppression of the TSH response to TRH. The goiter diminished in size significantly in 6 of the 12 patients during the 6 months of observation adn did not enlarge in any patient. The data indicate that suppression of the TSH response to TRH is a convenient technique to assess the adequacy of suppressive therapy of goiter.
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No pos
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No neg
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Retriever2230
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Pharmacokinetics and acetylation of sulfa-2-monomethoxine in humans.
In humans sulfa-2-monomethoxine (S) is metabolized by N4-acetylation (39.9 +/- 8.0 per cent). After an oral dose, S is eliminated biphasically (t1/2, 5.2 +/- 1.6 h and 13.2 +/- 3.4 h) which is similar in both fast and slow acetylators. The metabolite N4-acetylsulfa-2-monomethoxine (N4) is eliminated monophasically (t1/2, 30.0 +/- 5.7 h). The intrinsic mean residence time (MRT) of N4 is 33.5 +/- 8.8 h. The mean total body clearance of S is 11.6 +/- 2.7 ml min-1, and the Vdss is 12.3 +/- 1.01. The renal clearance of S during the first day was twice as high as on the following days for two of the six volunteers (8 vs 4 ml min-1). The renal clearance of N4 during the first day, for four out of the six volunteers, was twice as high as on the following days (8 vs 4 ml min-1). The protein binding of S is 95 per cent and that of its conjugate N4 98 per cent. Approximately 80 per cent of the oral dose of S is excreted in the urine as parent drug (41.0 +/- 6.2 per cent) and as N4 acetyl conjugate (39.9 +/- 8.0 per cent).
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No pos
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No neg
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Retriever2231
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Do allergens play a role in early childhood asthma?
What we know: Sensitisation to indoor allergens (house-dust mite, cat) is related to the level of exposure to these allergens in early childhood. The prevalence of asthma in childhood is independent of allergen exposure in early life. Asthma occurs in a substantial number of young children in the absence of allergen sensitisation. Asthma and allergic sensitisation have increased in recent decades, but there is no conclusive evidence that this is due to changes in environmental allergens. What we need to know: Have changes in environmental allergens contributed to the increasing incidence of asthma in recent decades? Is early childhood asthma (or certain subtypes of asthma) an allergen-induced disease? Is it possible to modify asthma by environmental allergen manipulation in early childhood? Is it possible to modulate the immune response to allergens in a favourable direction in early childhood?
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No pos
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No neg
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Retriever2232
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High-Frequency Electrical Modulation of the Superior Ovarian Nerve as a Treatment of Polycystic Ovary Syndrome in the Rat.
The polycystic ovary syndrome (PCOS) is the most prevalent ovarian pathology in women, with excessive sympathetic activity in the superior ovarian nerve (SON) playing an important role in inducing the PCOS symptoms in the rats and humans. Our previous studies have shown that surgical transection of the SON can reverse the disease progression, prompting us to explore the effect of the kilohertz frequency alternating current (KHFAC) modulation as a method of reversible non-surgical suppression of the nerve activity in the rodent model of PCOS. 56 animals were randomly allocated to three groups: the Control group (n = 18), the PCOS group (n = 15), and the PCOS + KHFAC group (n = 23). The physiological, anatomical, and biochemical parameters of ovarian function were evaluated during the progression of the experimentally-induced PCOS and during long-term KHFAC modulation applied for 2-3 weeks. The KHFAC modulation has been able to reverse the pathological changes in assessed PCOS parameters, namely the irregular or absent estrous cycling, formation of ovarian cysts, reduction in the number of corpora lutea, and ovarian norepinephrine concentration. The fertility capacity was similar in the PCOS and the PCOS + KHFAC groups, indicating the safety of KHFAC modulation approach. In summary, these results suggest that the KHFAC modulation approach of suppressing the SON activity could become a useful treatment modality for PCOS and potentially other pathological ovarian conditions.
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No pos
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No neg
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Retriever2233
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Fractionation of a hyaluronic acid preparation in a density gradient. The isolation and identification of a chondroitin sulphate.
1. Following the suggestion of Nichol, Ogston & Preston (1967) that hyaluronic acid, prepared by filtration from ox synovial fluid, contains a component of high density, such material has been detected and isolated by equilibrium sedimentation in a density gradient of caesium chloride. 2. This material (fraction III) has been characterized as a chondroitin sulphate-protein complex of average molecular weight about 250000. Its amino acid pattern is characteristic of such complexes present in cartilage. It contains a proportion of glucosamine (as well as galactosamine); this is not due to contamination with hyaluronic acid. 3. Preliminary findings on fraction I (low density) and fraction II (intermediate density) suggest that these consist chiefly of protein and hyaluronic acid respectively.
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No pos
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No neg
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Retriever2234
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Posterior open-door laminoplasty secured with titanium miniplates vs anchors: a comparative study of clinical efficacy and cervical sagittal balance.
OBJECTIVE
Posterior open-door laminoplasty (PODL) is a common procedure for treating multilevel cervical spondylotic myelopathy (MCSM). Little information is available regarding the cervical sagittal balance and surgical efficacy of PODL when securing with different methods. Therefore, this study aims to investigate the clinical outcomes and the changes in cervical sagittal parameters and balance associated with PODL secured with titanium miniplates vs anchors.
METHOD
A retrospective analysis was performed on the clinical data of 79 patients with MCSM who were treated in our institution from January 2015 to December 2016. Among them, 42 patients were treated by PODL secured with titanium miniplates (group A) and 37 patients by PODL secured with anchors (group B). Surgical time, intraoperative blood loss, hospital stay, hospitalized cost, VAS scores of neck pain, JOA scores, neck disability index (NDI), and improvement rate of spinal neurological function (IRNF) were recorded before surgery and at 12 months after surgery. Before surgery, at 1 month and 2 years after surgery, the following radiological parameters were recorded and compared on the lateral cervical X-ray images: the distance from the vertical axis of C2 sagittal plane to the posterior superior edge of C7 (C2-7 SVA), the inclusion angle of tangent between C2 and C7 trailing edge (C2-7 Cobb angle), and the intersection angle between the upper edge of T1 and the horizontal line (T1 Slope).
RESULT
Comparing the two groups, there were no significant differences in surgical time, intraoperative blood loss, hospital stay, VAS, JOA, and NDI scores before surgery (P > 0.05); however, the hospitalized cost of group A were much higher than those of the group B (P < 0.05). At 2 years after surgery in the two groups, there was a significant reduction in VAS and NDI scores (P < 0.05), and JOA scores increased significantly (P < 0.05). In addition, there were no significant differences in VAS, JOA and IRNF between the two groups (P > 0.05); however, NDI scores of group A were better than those of group B (P < 0.05). In radiological parameters, before surgery, the two groups showed no significant differences in C2-7 SVA, C2-7 Cobb angle, and T1 slope (P > 0.05); however, after surgery, C2-7 SVA and T1 slope increased (P < 0.05), while C2-7 Cobb angle decreased (P < 0.05). At 2 years after surgery, the two groups did not differ significantly in C2-7 Cobb angle and T1 slope (P > 0.05), while C2-7 SVA of group A was superior to that of group B (P < 0.05). The difference value of C2-7 SVA measured before and after surgery was correlated negatively with that of NDI scores (P < 0.05).
CONCLUSION
PODL secured with titanium miniplates or anchors achieved good clinical efficacy in the treatment of MCSM. However, the patients with miniplates feel a better cervical functional status, while those with anchors spend less on hospitalization. Both methods lead to anteversion of cervical spine, but cervical sagittal balance after miniplates is better than that of anchors.
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No pos
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No neg
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Retriever2235
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Investigating the important correlates of maternal education and childhood malaria infections.
The relationship between maternal education and child health has intrigued researchers for decades. This study explored the interaction between maternal education and childhood malaria infection. Cross-sectional survey data from three African countries were used. Descriptive analysis and multivariate logistic regression models were completed in line with identified correlates. Marginal effects and Oaxaca decomposition analysis on maternal education and childhood malaria infection were also estimated. Children with mothers whose education level was beyond primary school were 4.7% less likely to be malaria-positive (P < 0.001). The Oaxaca decomposition analysis exhibited an 8% gap in childhood malaria infection for educated and uneducated mothers. Over 60% of the gap was explained by differences in household wealth (26%), household place of domicile (21%), malaria transmission intensities (14%), and media exposure (12%). All other correlates accounted for only 27%. The full adjusted model showed a robust and significant relationship between maternal education and childhood malaria infection.
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No pos
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No neg
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Retriever2236
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[Acute confusional syndrome due to acute nicotine withdrawal].
Delirium or acute confusional state among hospitalized patients is a frequent and serious problem. It is characterized by acute onset symptoms, fluctuating course, impaired attention, unorganized thinking, and altered level of consciousness. Delirium, as a manifestation of acute nicotine withdrawal syndrome has been reported in the reviewed literature only in eight cases. We report the case of a heavy smoker admitted because of a reagudization of his chronic obstructive pulmonary disease. At the third day of nicotine abstinence, he developed delirium with a rapid improvement of his symptoms after treatment with a transdermal nicotine patch. This description suggests that in hospitalized heavy smokers who develop delirium with agitation, a simple trial with a nicotine patch can offer a dramatic therapeutic response in a few hours, constituting additionally a confirmatory test. The recognition of delirium as a manifestation of nicotine withdrawal could allow to determine the origin of symptoms and to apply the appropriate therapy, in certain complex cases that now remain undiagnosed.
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No pos
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No neg
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Retriever2237
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The high burden of injuries in South Africa.
OBJECTIVE
To estimate the magnitude and characteristics of the injury burden in South Africa within a global context.
METHODS
The Actuarial Society of South Africa demographic and AIDS model (ASSA 2002) - calibrated to survey, census and adjusted vital registration data - was used to calculate the total number of deaths in 2000. Causes of death were determined from the National Injury Mortality Surveillance System profile. Injury death rates and years of life lost (YLL) were estimated using the Global Burden of Disease methodology. National years lived with disability (YLDs) were calculated by applying a ratio between YLLs and YLDs found in a local injury data source, the Cape Metropole Study. Mortality and disability-adjusted life years' (DALYs) rates were compared with African and global estimates.
FINDINGS
Interpersonal violence dominated the South African injury profile with age-standardized mortality rates at seven times the global rate. Injuries were the second-leading cause of loss of healthy life, accounting for 14.3% of all DALYs in South Africa in 2000. Road traffic injuries (RTIs) are the leading cause of injury in most regions of the world but South Africa has exceedingly high numbers - double the global rate.
CONCLUSION
Injuries are an important public health issue in South Africa. Social and economic determinants of violence, many a legacy of apartheid policies, must be addressed to reduce inequalities in society and build community cohesion. Multisectoral interventions to reduce traffic injuries are also needed. We highlight this heavy burden to stress the need for effective prevention programmes.
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No pos
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No neg
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Retriever2238
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Case Report: Acute Limb Ischaemia and Gangrene associated with Peripartum Cardiomyopathy.
UNLABELLED
Thromboembolic complications are frequent in patients with peripartum cardiomyopathy (PPCM). Peripheral artery occlusions are however rare. This case report describes a 30-year-old grand multiparous woman with PPCM complicated by acute lower limb ischaemia and gangrene. This followed left intraventricular thrombi despite maintenance of sinus rhythm. We suspect that the thrombosis is caused by the hypercoagulable state of peripartum period, ventricular dilatation and hypokinesis. The impacts of economic and sociocultural factors in the management of this rare complication of PPCM in a resource depleted nation are highlighted.
KEYWORDS
peripartum cardiomyopathy, limb ischaemia.
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No pos
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No neg
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Retriever2239
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Contemporary trends in management of stage 1 seminoma.
PURPOSE
Surveillance is now the preferred treatment strategy for patients with stage 1A/1B seminoma as reflected by the National Comprehensive Cancer Network guidelines. In this study, we aimed to describe trends in adjuvant management strategy for stage 1A/B seminoma from 2004 to 2016 using the National Cancer Database.
MATERIALS AND METHODS
The database was queried for patients diagnosed with stage 1A/1B seminoma between 2004 and 2016. Staging was determined using the American Joint Committee on Cancer guidelines. Surveillance was defined as no treatment with chemotherapy or radiation within 60 days of diagnosis. Proportions of cancer patients utilizing surveillance, radiation, and single-agent chemotherapy were summarized annually. Kaplan-Meier survival analysis was used to compare overall survival between groups.
RESULTS
8,686 patients with stage 1A/1B seminoma met inclusion criteria over the course of the study period. Overall, 3,004 (34.6%) patients began adjuvant chemotherapy or radiation within 60 days. Utilization of surveillance increased from 39.8% in 2004 to 86.8% in 2016 while utilization of radiation decreased from 59.7% to 4.6%. High-volume centers adopted surveillance earlier than low-volume centers.
CONCLUSION
This study describes trends in utilization of surveillance, chemotherapy, and radiotherapy for stage 1A/1B seminoma over 12 years. A major shift from utilization of adjuvant treatment to surveillance in patients with stage 1A/B seminoma is observed in this large national cancer database; a minority of patients now receive adjuvant treatment and risk-related toxicities. Survival analysis reveals similar survival at a median 5-year follow-up. The results provide insight into the time needed for clinical practice to adopt the preferred approach of surveillance over the time period studied.
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No pos
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No neg
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Retriever2240
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Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease.
We provide a comprehensive field synopsis of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD). A systematic review was performed and included 84 genetic association studies reporting data for 183 polymorphisms in 71 genes. Meta-analyses were conducted for 20 SNPs in 10 genes of paediatric Crohn's disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC). Five epigenetic studies were also included, but formal meta-analysis was not possible. Venice criteria and Bayesian false discovery probability test were applied to assess the credibility of associations. Nine SNPs in 4 genes were considered to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs12521868, rs26313667, rs1800629) were not previously identified in paediatric GWAS. Differential DNA methylation in NOD2 and TNF-α, dysregulated expression in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated. Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, with similar magnitudes of associations. Early onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic changes, but these findings need to be replicated. Further progress identifying genetic and epigenetic susceptibility of paediatric IBD will require international collaboration, population diversity and harmonization of protocols.
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No pos
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No neg
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Retriever2241
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Dietetics training for American Indians and Alaskan natives.
The response to training has been enthusiastic. Even in these times of limited funds, applications to attend training exceed the available space. From the first class in October 1968 through September 1982, nearly 1,300 Indian and Alaskan native hospital food service employees and employees representing tribal programs throughout the country have received training from the courses and workshops provided by the Nutrition and Dietetics Training Program. With the increasing involvement of Native Americans in their own health care programs, the need for training in foods and nutrition will continue.
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No pos
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No neg
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Retriever2242
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Anaesthesia and hospital links: strengthening healthcare through South-North hospital partnerships.
Health services can respond to the needs of the poorest people in developing countries if those who work in the front line of health care are supported and motivated and if development needs in services and training programmes can be filled. This can be achieved when a Health Link between a southern hospital and/or training school and its northern counterpart is designed to build a disciplined and long-term programme of staff development including the needs of anaesthetic services, which meets the needs identified by the southern partner. Development of anaesthetic practice is best carried out in the context of an institution-wide Health Link where not only the staff and systems involved in anaesthesia but all the essential 'back office' or support services are also supported and developed.
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No pos
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No neg
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Retriever2243
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Time management practices for the dentist.
Many people have been trained from childhood up through dental or professional school to depend on others to structure their time. Dentists cannot afford to rely on someone else to decide how their time should be used. As an executive in charge of your own business, learn the behaviors that your new role requires. Learn appropriate skills for taking charge of your responsibilities. This will require experience-based training in small group dynamics and interpersonal communication along with the usual business skills. This does not mean you need to become an expert in these areas. It does mean you must enhance your personal development to the point of being able to separate what is comfortable behavior from what is effective behavior. Plan and organize your duties and work assignments to get the results you want and to get rid of the stress that occurs with crisis management. Coordinate your activities so that you are clear how they relate to the results you get. Control the different factors that may influence your ability to choose how you use the time available to you. The crucial factors are your objectives and priorities. Focus on developing the ability to lead and direct your auxiliaries for effective use of time.
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No pos
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No neg
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Retriever2244
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Comparison of carcinogenicity of N-alkyl-N'-nitro-N-nitroso-guanidines.
Carcinogenicity of seven homologs of N-alkyl-N'-nitrosoguanidine (N-alkyl-NNG), namely, N-methyl-NNG, N-propyl-NNG, N-butyl-NNG, N-isobutyl-NNG, N-pentyl-NNG, and N-hexyl-NNG, was examined by injecting the compounds subcutaneously into rats. All of them except N-isobutyl-NNG and N-hexyl-NNG were carcinogenic, but N-ethyl-NNG followed by N-methyl-NNG were stronger carcinogens than those with longer alkyl chains.
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No pos
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No neg
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Retriever2245
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A preliminary analysis of combination therapy with vincristine, adriamycin, and prednimustine (VAP) in advanced breast cancer: a phase II study.
Between March 1984 and May 1985, 29 patients with metastatic breast cancer and high-risk prognostic factors were treated with vincristine, 1.4 mg/m2 IV on day 1, Adriamycin, 40 mg/m2 IV on day 1, and prednimustine, 100 mg/m2 PO on days 3 to 7. Courses were repeated every 3 weeks. At the present time, 26 patients are evaluable for tumor response; 29 are evaluable for toxicity. Fourteen of 26 patients (53.8%) achieved a partial response lasting 2 to 9 months (median 5.5+). A complete response was not recorded. Ten of 26 patients (38.5%) had stable disease; two patients (7.7%) showed a primary tumor progression. Most common side effects were nausea, vomiting, and alopecia, all generally mild to moderate. Fourteen of 29 patients developed leukocytopenia, mainly of WHO grade 1; thrombocytopenia was registered in one patient only and a fall of hemoglobin in three patients only. In 15 patients, no hematologic toxicity occurred. These preliminary data suggest good antitumor activity and acceptable toxicity for vincristine-Adriamycin-prednimustine in patients with metastatic breast cancer.
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No pos
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No neg
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Retriever2246
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Effect on immunologic and other indices of adjuvant cytotoxic chemotherapy including melphalan in breast cancer.
Thirty patients with histologically proven node-positive early breast cancer (Stage II) were treated by total mastectomy and axillary clearance and adjuvant chemotherapy regimens including melphalan for 1 year. These patients were studied sequentially, at 3-month intervals, for up to 2 years to assess effects of cytotoxic drugs on immune function, and to determine whether any changes in immune function were related to recurrence. All indices were in the normal range before chemotherapy. The most marked and long-lasting effects of chemotherapy were on numbers of circulating T-cells and B-cells. Mean counts +/- one standard error (X 10(6)/ml) for T-cells before and 12 months after stopping chemotherapy were 1.537 +/- 0.118 and 0.874 +/- 0.120 (P less than 0.01), and for B-cells 0.345 +/- 0.060 and 0.207 +/- 0.030 (P less than 0.01). Functional indices of T-cell and B-cell competence were less compromised than values for cell counts and, in contrast, recovery occurred either during or within 3 months of stopping chemotherapy. This held for both T-cell function measured by delayed-type hypersensitivity (DTH) responsiveness to five recall antigens and mitogenic responsiveness to phytohemagglutinin, and for B-cell function measured by titration of blood group isohemagglutinins. After 4 years the 30 subjects were divided into groups according to whether there was recurrence of cancer (14) or no recurrence (16); the only index predictive of recurrence was depression of DTH to recall antigens. Thus it was found that cytotoxic chemotherapy with melphalan appears to cause long-lasting depression of cell counts but only short-lasting depression of functional indices of immunocompetence, and that levels of immunologic indices during chemotherapy are mostly nonpredictive of recurrence of cancer. The results prompt some caution in the use of adjuvant chemotherapy, at least with melphalan.
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No pos
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No neg
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Retriever2247
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Captan exposure and evaluation of a pesticide exposure algorithm among orchard pesticide applicators in the Agricultural Health Study.
Pesticide exposure assessment in the Agricultural Health Study (AHS) has relied upon two exposure metrics: lifetime exposure days and intensity-weighted lifetime exposure days, the latter incorporating an intensity score computed from a questionnaire-based algorithm. We evaluated this algorithm using actual fungicide exposure measurements from AHS private orchard applicators. Captan was selected as a marker of fungicide exposure. Seventy-four applicators from North Carolina and Iowa growing apples and/or peaches were sampled on 2 days they applied captan in 2002 and 2003. Personal air, hand rinse, 10 dermal patches, a pre-application first-morning urine and a subsequent 24-h urine sample were collected from each applicator per day. Environmental samples were analyzed for captan, and urine samples were analyzed for cis-1,2,3,6-tetrahydrophthalimide (THPI). Task and personal protective equipment information needed to compute an individual's algorithm score was also collected. Differences in analyte detection frequency were tested in a repeated logistic regression model. Mixed-effects models using maximum-likelihood estimation were employed to estimate geometric mean exposures and to evaluate the measured exposure data against the algorithm. In general, captan and THPI were detected significantly more frequently in environmental and urine samples collected from applicators who used air blast sprayers as compared to those who hand sprayed. The AHS pesticide exposure intensity algorithm, while significantly or marginally predictive of thigh and forearm captan exposure, respectively, did not predict air, hand rinse or urinary THPI exposures. The algorithm's lack of fit with some exposure measures among orchard fungicide applicators may be due in part to the assignment of equal exposure weights to air blast and hand spray application methods in the current algorithm. Some modification of the algorithm is suggested by these results.
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No pos
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No neg
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Retriever2248
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Combinatorics of γ-structures.
In this article we study canonical γ-structures, a class of RNA pseudoknot structures that plays a key role in the context of polynomial time folding of RNA pseudoknot structures. A γ-structure is composed of specific building blocks that have topological genus less than or equal to γ, where composition means concatenation and nesting of such blocks. Our main result is the derivation of the generating function of γ-structures via symbolic enumeration using so called irreducible shadows. We furthermore recursively compute the generating polynomials of irreducible shadows of genus ≤ γ. The γ-structures are constructed via γ-matchings. For 1 ≤ γ ≤ 10, we compute Puiseux expansions at the unique, dominant singularities, allowing us to derive simple asymptotic formulas for the number of γ-structures.
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No pos
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No neg
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Retriever2249
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Tumor-Educated Platelets Facilitate Thrombus Formation Through Migration.
Platelets are small anucleate cells that circulate in the blood and form thrombi. Tumor-educated platelets are the platelets derived from cancer patients. Although many have reported that tumor-educated platelets are associated with cancer-associated thrombosis, their function in this process is poorly understood. Here we first collect the clinical data from 100 different cancer patients, showing that cancer patients are in a hypercoagulable state. Our experiment shows that tumor-educated platelets from melanoma-burdened mouse models can migrate faster and longer, forming more clots (thrombus). However, the plasma from tumor mice can inhibit platelet migration. The RNA sequence profile of tumor-educated platelets shows that many genes associated with cell migration and cell skeleton expressed significantly higher. Our research offers a new insight into the tumor-educated platelets to better understand the thrombus formation.
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No pos
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No neg
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Retriever2250
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The functional roles of psyllid abundance and assemblage on bird-associated forest defoliation.
Fluctuations in the abundance of insect herbivores and the severity of damage they cause to their hosts are key factors affecting tree health and trophic interactions. Bell miner associated dieback (BMAD) is a trophic cascade involving eucalypt trees, psyllids and bell miners. Bell miners are a territorial species of bird that reduce insectivorous bird diversity, thereby increasing psyllid abundances. The role of psyllids in BMAD is debated, primarily because psyllid host specificity, genus, defoliation potential and/or lerp composition have been conflated or unexplored. This study documented psyllid communities and canopy structure of four eucalypt hosts (Eucalyptus bridgesiana, E. caliginosa, E. propinqua and E. siderophloia) in BMAD and non-BMAD-affected forests in northern New South Wales. Psyllid abundances were significantly higher in BMAD-affected forests. However, psyllid assemblages did not differ between forest types which contrasts with an influential hypothesis concerning bell miner farming of psyllids that produce sugary lerps (Glycaspis species). Importantly, psyllid communities differed among species of eucalypt host. Hosts supporting higher abundances of Cardiaspina tended to have a stronger negative relationship between canopy health and psyllid abundances than other host trees. Cardiaspina were also found on older leaves and associated with more leaf damage than other psyllids. Unlike most other psyllid genera, Cardiaspina initiate premature foliar senescence leading to defoliation which ultimately changes the age structure of leaves of the canopies of affected trees. Our study supports the functional linkage between psyllid assemblages, their relative abundances and defoliation potential to bottom-up mechanisms behind a bird-associated trophic cascade.
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No pos
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No neg
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Retriever2251
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Confirmation of extended-spectrum beta-lactamase-producing Serratia marcescens: preliminary report from Taiwan.
Although Serratia marcescens is a common cause of nosocomial infection in Taiwan, strains producing extended-spectrum beta-lactamases (ESBLs) are rare. We detected four clinical isolates of S. marcescens from Taiwan that exhibited resistance to cefotaxime (MICs, > 256 microg/ml) and cefepime (MICs, > or = 32 microg/ml), but were susceptible to imipenem and meropenem. Transconjugants revealed similar MIC profiles when compared to the parental strains. Isoelectric focusing revealed one major transferable beta-lactamase (pI 8.4), which was further identified as CTX-M-3 by polymerase chain reaction and gene sequencing. An AmpC-like enzyme (pI 8.8) was not transferable. All four isolates had significant MIC reductions of > or =3 log(2) dilutions for cefepime in the presence of clavulanic acid, compatible with the presence of an ESBL (CTX-M-3). Clavulanate did not significantly reduce the cefotaxime MIC for one isolate that may co-produce high-level AmpC beta-lactamase (pI 8.8). Since high-level AmpC expression has minimal effect on the activity of cefepime, isolates co-producing AmpC beta-lactamase may be recognized as additional ESBL producers by using cefepime as an ESBL screening agent.
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No pos
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No neg
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Retriever2252
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Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer.
BACKGROUND
Colorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors.
METHODS
We sequenced nine tumor regions and 88 single cells from two rectal cancer patients with tumors of the same molecular classification and characterized their mutation profiles and somatic copy number alterations (SCNAs) at the multi-region and the single-cell levels.
RESULTS
A variable extent of genomic heterogeneity was observed between the two patients, and the degree of ITH increased when analyzed on the single-cell level. We found that major SCNAs were early events in cancer development and inherited steadily. Single-cell sequencing revealed mutations and SCNAs which were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer at regional and single-cell resolution and demonstrated that variable heterogeneity existed in two patients. The mutational scenarios and SCNA profiles of two patients with treatment naïve from the same molecular subtype are quite different.
CONCLUSIONS
Our results suggest each tumor possesses its own architecture, which may result in different diagnosis, prognosis, and drug responses. Remarkable ITH exists in the two patients we have studied, providing a preliminary impression of ITH in rectal cancer.
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No pos
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No neg
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Retriever2253
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Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of Sam68.
Adenomatous polyposis coli (APC) is a tumor suppressor protein commonly mutated in colorectal tumors. APC plays important roles in Wnt signaling and other cellular processes. Here, we present the crystal structure of the armadillo repeat (Arm) domain of APC, which facilitates the binding of APC to various proteins. APC-Arm forms a superhelix with a positively charged groove. We also determined the structure of the complex of APC-Arm with the tyrosine-rich (YY) domain of the Src-associated in mitosis, 68 kDa protein (Sam68), which regulates TCF-1 alternative splicing. Sam68-YY forms numerous interactions with the residues on the groove and is thereby fixed in a bent conformation. We assessed the effects of mutations and phosphorylation on complex formation between APC-Arm and Sam68-YY. Structural comparisons revealed different modes of ligand recognition between the Arm domains of APC and other Arm-containing proteins.
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No pos
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No neg
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Retriever2254
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New concept for CTO recanalization using controlled antegrade and retrograde subintimal tracking: the CART technique.
OBJECTIVES
To demonstrate the safety and feasibility of a new concept for CTO recanalization using a controlled antegrade and retrograde subintimal tracking technique (CART technique).
BACKGROUND
A successful percutaneous recanalization of chronic coronary occlusions results in improved survival, as well as enhanced left ventricular function, reduction in angina, and improved exercise tolerance. However, successful recanalization of CTOs is still not optimal, and needs further improvements.
METHODS
Ten patients with a CTO underwent the CART procedure. This technique combines the simultaneous use of the antegrade and retrograde approaches. A subintimal dissection is created antegradely and retrogradely, which allows the operator to limit the extension of the subintimal dissection in the CTO portion. A retrograde approach means that the occlusion site is approached in a retrograde fashion through the best collateral channel from any other patent coronary artery.
RESULTS
The occlusion site was located in the RCA in 9 patients, and in the LAD in 1 patient. CTO duration varied from 7 to 84 months. Vessel recanalization was achieved in all patients. In all cases, the subintimal dissection was limited to the CTO region. No complications occurred in the collateral channel used for the retrograde approach. There were no in-hospital major adverse cardiac events.
CONCLUSIONS
The CART technique is feasible, safe, and has a high success rate.
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No pos
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No neg
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Retriever2255
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In vitro and in vivo effectiveness evaluation of balofloxacin in experimental Staphylococcus aureus keratitis.
PURPOSE
To evaluate the effectiveness of balofloxacin for treatment of experimental Staphylococcus aureus keratitis.
METHODS
In vitro testing compared the cellular toxicity of and bacterial susceptibility to balofloxacin and levofloxacin in human corneal epithelial cells (HCECs). For in vivo testing, experimental bacterial keratitis was induced and treated with balofloxacin eye drops (0.5%) and levofloxacin eye drops (0.5%).
RESULTS
In vitro toxicity examinations showed that balofloxacin, as well as levofloxacin, had low cytotoxicity in HCECs. Balofloxacin eye drops (0.5%) also showed a similar relative cytotoxicity to levofloxacin eye drops (0.5%). In bacterial susceptibility examinations, both balofloxacin and levofloxacin significantly reduced S. aureus compared with the untreated control (P<0.001 for both balofloxacin and levofloxacin). Balofloxacin was more effective than levofloxacin in the treatment of S. aureus bacterial keratitis (P<0.05). In experimental bacterial keratitis treatment testing, balofloxacin was also more effective than levofloxacin with respect to the parameters of physiological score, histological observation, and bacterial quantitation (P<0.05).
CONCLUSIONS
Balofloxacin was safe in the treatment of S. aureus bacterial keratitis, and more effective than levofloxacin. Therefore, balofloxacin was shown to have potential clinical value in ophthalmic local application.
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No pos
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No neg
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Retriever2256
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Axial subcutaneous scalp flaps in the reconstruction of the anterior cranial fossa.
A major concern following combined craniofacial resection of neoplasms involving the floor of the anterior cranial fossa is the creation of a watertight separation between the contents of the anterior cranial fossa and the upper aerodigestive tract. The reconstructive technique should satisfy several goals, which we will outline. The axial subcutaneous scalp flap meets these goals and has proved to be useful in reconstruction of the anterior skull base. We used the axial subcutaneous scalp flap for this purpose in three patients. Herein, we report our experience and emphasize the importance of the vascular pattern of the anterior scalp.
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No pos
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No neg
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Retriever2257
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Cues to deception: can complications, common knowledge details, and self-handicapping strategies discriminate between truths, embedded lies and outright lies in an Italian-speaking sample?
Deception research has shown that analysing verbal content can be effective to distinguish between truths and lies. However, most verbal cues are cues to truthfulness (truth tellers report the cue more than lie tellers), whereas cues to deception (lie tellers report the cue more than truth tellers) are largely absent. The complication approach, measuring complications (cue to truthfulness), common knowledge details (cue to deception), self-handicapping strategies (cue to deception), and the ratio of complications, aims to fill this gap in the literature. The present experiment examined the effectiveness of the complication approach when varying the amount of lying, with an Italian sample. Seventy-eight participants were assigned to one of three different experimental conditions: Truth tellers (telling the truth about the event), embedders (providing a mixture of truthful and false information) and outright lie tellers (providing false information). Participants were interviewed about a past experience concerning an out of the ordinary event. Complications discriminated truth tellers from lie tellers. The absence of significant effects for common knowledge details and self-handicapping strategies, the limitations of the experiment and suggestions for future research are discussed.
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No pos
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No neg
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Retriever2258
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Radiofrequency ablation before intratumoral injection of (131)I-chTNT improves the tumor-to-normal tissue ratio in solid VX2 tumor.
PURPOSE
This study was aimed to investigate whether the tumor necrosis induced by radiofrequency ablation (RFA) can improve the ratio of tumor-to-normal tissue (T/NT) after intratumoral injection of (131)I-chTNT.
MATERIALS AND METHOD
Eighteen New Zealand rabbits bearing VX2 tumor on the thigh were randomly divided into two treatment groups (control group: intratumoral injection of (131)I-chTNT alone; RFA group: RFA + intratumoral injection of (131)I-chTNT 3 days after RFA) and each group was further divided into three subgroups I, II, and III (1-2 cm, 2-3 cm, and 3-4 cm in maximum diameter, respectively), by the tumor size. SPECT was performed to evaluate the T/NT on days 1, 8, and 15 after (131)I-chTNT injection.
RESULTS
After treatment, all rabbits underwent the SPECT whole-body scan and the T/NT was analyzed. The results showed that T/NT in the RFA group (55.45±41.83) was significantly higher compared with the control group (7.23±5.61) (F=18.89, p=0.001). Meanwhile, a linear ascending trend was found for T/NT in the RFA group along with the follow-up time (r=0.47, p=0.01). The tumor size or the dose of (131)I-TNT injection had no significant effect on the variation of T/NT in both groups (p>0.05).
CONCLUSION
RFA before intratumoral injection of (131)I-chTNT can dramatically improve T/NT, demonstrating the potential application of this combination therapy.
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No pos
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No neg
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Retriever2259
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Prognostic significance of the depth of invasion relating to nodal metastases, parametrial extension, and cell types. A study of 628 cases with Stage IB, IIA, and IIB cervical carcinoma.
Depths of invasion by increments of 5 mm were evaluated as a prognostic factor in 628 patients after radical hysterectomy for Stage IB to IIB cervical carcinoma. Nodal metastases (N) were significantly increased when tumor invasion was deeper than 5, 10, and 30 mm. Parametrial extension (P) was significantly increased with 10-, 15-, and 25-mm invasion. In total, the corrected 5-year survival rates were significantly reduced with 20 and 30 mm invasion. However, survival rates were almost the same in N(-)P(-) cases, ranging from 96% to 100%. Reduction of the survival rates with 20-mm invasion was found in IIB, P(+), or N(-) cases, and with 30-mm invasion in IB, IIB, P(+), or N(+) cases. Subdivision by N or P factors revealed an evidence that in N(+) or P(+) cases, survival of patients with under 10-mm invasion was significantly poorer than that of cases with 10- to 15-mm invasion. These indicate that depth of invasion is a valuable prognostic factor in patients with nodal metastases or parametrial extension.
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No pos
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No neg
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Retriever2260
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iDHS-DSAMS: Identifying DNase I hypersensitive sites based on the dinucleotide property matrix and ensemble bagged tree.
DNase I hypersensitive site (DHS) is related to DNA regulatory elements, so the understanding of DHS sites is of great significance for biomedical research. However, traditional experiments are not very good at identifying recombinant sites of a large number of emerging DNA sequences by sequencing. Some machine learning methods have been proposed to identify DHS, but most methods ignore spatial autocorrelation of the DNA sequence. In this paper, we proposed a predictor called iDHS-DSAMS to identify DHS based on the benchmark datasets. We develop a feature extraction method called dinucleotide-based spatial autocorrelation (DSA). Then we use Min-Redundancy-Max-Relevance (mRMR) to remove irrelevant and redundant features and a 100-dimensional feature vector is selected. Finally, we utilize ensemble bagged tree as classifier, which is based on the oversampled datasets using SMOTE. Five-fold cross validation tests on two benchmark datasets indicate that the proposed method outperforms its existing counterparts on the individual accuracy (Acc), Matthews correlation coefficient (MCC), sensitivity (Sn) and specificity (Sp).
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No pos
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No neg
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Retriever2261
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Feasibility of repeat microdissection testicular sperm extraction within 6 months for non-obstructive azoospermia.
BACKGROUND
Microdissection testicular sperm extraction (mTESE) is the mainstay of sperm retrieval in men with non-obstructive azoospermia (NOA). Some experts believe that a resting period of ≥6 months is required between procedures to ensure better sperm retrieval rates and fewer complications. However, no scientific studies have investigated how long patients should wait before arranging a second mTESE procedure. This retrospective study aimed to evaluate whether good success rates are still achieved when a repeat mTESE procedure is performed within 6 months.
METHODS
Total 146 patients with NOA who underwent mTESE twice from the same testis between May 2012 and September 2019 were retrospectively collected. These patients were categorized into three groups according to the time interval between the two mTESE surgeries, with 44, 60, and 42 patients undergoing a repeat mTESE after <3 months (Group I), between 3 and 6 months (Group II), and >6 months (Group III) after the first procedure, respectively.
RESULTS
No significant differences were observed between groups in terms of patient characteristics and preoperative hormone profiles. Overall sperm retrieval rates did not differ among the three groups (93.2%, 90.0%, and 88.1% in groups I, II, and III, respectively (p=0.719)), nor did fertility outcomes, including rates of fertilization, biochemical pregnancy, clinical pregnancy, and cumulative live births.
CONCLUSION
Sperm retrieval rates for repeat mTESE procedures were consistently high, even when the second procedure was performed within 6 months of the first. Repeat mTESE within 6 months is not a limitation for patients with NOA, if required clinically.
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No pos
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No neg
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Retriever2262
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Factors associated with early postoperative exercise tolerance after living-donor liver transplantation.
BACKGROUND
Physical dysfunction, including exercise intolerance, is a major factor for delayed societal reintegration for patients who underwent living-donor liver transplantation (LDLT). However, what may contribute to early postoperative physical function is not well known. The purpose of this study is to elucidate the perioperative factors affecting early posttransplant exercise intolerance.
METHODS
103 consecutive patients who underwent LDLT were enrolled, and 68 patients were retrospectively analyzed. We examined the relationship between postoperative exercise tolerance evaluated by a 6-minute walking distance (6MWD) at discharge after surgery and demographic data, surgical information, preoperative physical function, clinical course, and the postoperative decline in physical function with univariate and multivariate analyses.
RESULTS
Almost all patients were discharged within 3 months after surgery. The postoperative 6MWD was 408 ± 94 m (68 [61-84]% of the predicted value), and patients who had a low %6MWD at discharge had significantly lower preoperative physical function than patients who had a high %6MWD at discharge (grip strength: 29.8 ± 8.9 kgf vs. 23.0 ± 8.8 kgf, P < .01, knee extensor strength: 138.9 ± 59.4 Nm vs. 95.2 ± 42.1 Nm, P < .01). Multivariate analysis revealed that preoperative knee extensor strength (standardized β = 0.35, P < .01) and first postoperative walking day (standardized β = -0.22, P = .04) were independently associated with the postoperative %6MWD.
CONCLUSION
These results suggest that maintaining preoperative muscle strength and allowing for early postoperative mobilization might help to enhance the recovery of physical function and facilitate the patient's social reintegration after LDLT.
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No pos
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No neg
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Retriever2263
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The complex relationship between depressive symptoms and functional limitations in community-dwelling older adults: the impact of subthreshold depression.
BACKGROUND
Depressive symptoms above screening thresholds have been shown to predict functional decline in older adults. Less is known about the impact of subthreshold depression, and whether more symptoms confer significantly greater risk compared to fewer symptoms.
METHOD
Using data from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE) collected over 10 years, we used repeated-measures mixed models to predict functional change by depression status at the prior (index) in-person interview. Depressive symptoms were measured using a modified version of the Center for Epidemiologic Studies Depression Scale (CES-D). Subthreshold depression was operationalized as 6-8 symptoms and CES-D-defined depression as 9-20 symptoms in the previous week. Three domains of functional status were assessed at the subsequent in-person interview: limitations in basic activities of daily living (ADL), instrumental ADL (IADL) and mobility.
RESULTS
Controlling for race, sex, age, education, marital status, cognitive status, health status, self-perceived health, perceived social support and functional status at the index interview, having 6 depressive symptoms predicted an increase of 0.12 IADL limitations 3-4 years later (p=0.03). The incremental effect of CES-D-defined depression (9 symptoms compared to 6-8 symptoms) was not significant, suggesting that the effect of more symptomatic depression did not add to that of subthreshold depression. CES-D score modeled as a continuous variable predicted functional change for all domains, but the relationship was not linear, supporting a possible threshold effect.
CONCLUSIONS
The relationship between depressive symptoms and functional change is complex, not necessarily linear, and may vary by tasks assessed.
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No pos
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No neg
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Retriever2264
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Pre- and post-sexual exposure prophylaxis of HIV: An update.
Pitfalls in current HIV prevention strategies include late HIV testing, vulnerability among youth and females; lack of emphasis on treatment, low acceptance of circumcision, and nonavailability of protective vaccines. Continuing high-risk sexual behavior, forceful sex, coercive and nonconsensual sex, rape, and unprotected sexual activities make women the most vulnerable to acquisition of sexually transmitted infection/HIV and necessitates a more radical approach of prevention in high-risk individuals who do not have HIV. Preexposure prophylaxis is defined as the administration of antiretroviral drugs to an uninfected person before potential HIV exposure to reduce the risk of infection and continued during risk. The rationale of this approach is to administer preventive dose of drug(s) before exposure to HIV so the moment virus enters the body, HIV replication is inhibited and HIV is not able to establish permanent infection. Postexposure prophylaxis (PEP) following potential sexual exposure is an important form of nonoccupational PEP which is an emergency intervention to abort HIV acquisition arising from exposure to HIV-infected blood or potentially infectious bodily fluids following sexual exposure.
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No pos
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No neg
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Retriever2265
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Fetal arrhythmias: diagnosis and treatment.
Fetal arrhythmias are common, and they may resolve spontaneously in majority of the cases. Sustained fetal arrhythmias associated with major structural heart disorders, hydrops fetalis, and fetal heart failure warrant intrauterine pharmaceutical conversion of heart rhythm or early pacemaker implant in order to avoid fetal demise. Fetal atrial flutter (AF) and supraventricular tachycardia (SVT) resemble in terms of the effects of intrauterine therapies. Digoxin is more suitable for rhythm conversion of fetal AF and SVT in fetuses free of hydrops fetalis, while sotalol shows better effects for those with hydrops fetalis. In fetal cases of atrioventricular blocks, an etiological treatment for the maternal antibody exposure by steroids could be an alternative remedy. In this article, the clinical diagnosis and treatment of fetal arrhythmias are presented, and advantages and disadvantages of antiarrhythmic agents for fetal arrhythmias are compared.
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No pos
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No neg
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Retriever2266
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A trypanosome-soluble factor induces IP3 formation, intracellular Ca2+ mobilization and microfilament rearrangement in host cells.
Lysosomes are recruited to the invasion site during host cell entry by Trypanosoma cruzi, an unusual process suggestive of the triggering of signal transduction mechanisms. Previous studies showed that trypomastigotes, but not the noninfective epimastigotes, contain a proteolytically generated trypomastigote factor (PGTF) that induces intracellular free Ca2+ transients in several mammalian cell types. Using confocal time-lapse imaging of normal rat kidney (NRK) fibroblasts loaded with the Ca(2+)-sensitive dye fluo-3, we show that the initial intracellular free Ca(2+) concentration ([Ca2+]i) transient detected a few seconds after exposure to trypomastigote extracts is a result of Ca2+ release from intracellular stores. Removal of Ca2+ from the extracellular medium or inhibition of Ca2+ channels with NiCl2 did not affect the response to PGTF, while depletion of intracellular stores with thapsigargin abolished it. [Ca2+]i transients induced by PGTF were shown to be coupled to the activity of phospholipase C (PLC), since the specific inhibitor U73122 completely blocked the response, while its inactive analogue U73343 had no effect. In addition, polyphosphoinositide hydrolysis and inositol 1,4,5-trisphosphate (IP3) were detected upon cell stimulation with PGTF, suggesting the participation of IP3-sensitive intracellular Ca2+ channels. An immediate effect of the signaling induced by PGTF and live trypomastigotes was a rapid and transient reorganization of host cell microfilaments. The redistribution of F-actin appeared to be a direct consequence of increased [Ca2+]i, since thrombin and the Ca2+ ionophore ionomycin produced a similar effect, with a time course that corresponded to the kinetics of the elevation in [Ca2+]i. These observations support the hypothesis that PGTF-induced disassembly of the cortical actin cytoskeleton may play a role in T. cruzi invasion, by facilitating lysosome access to the invasion site. Taken together, our findings suggest that the proteolytically generated trypomastigote factor PGTF is a novel agonist that acts through the PLC/phosphoinositide signaling pathway of mammalian cells.
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No pos
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No neg
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Retriever2267
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Sesquiterpenes from Streptomyces qinglanensis and Their Cytotoxic Activity.
Nine sesquiterpenes, including eight pentalenenes (1-8) and one bolinane derivative (9), were isolated from the culture broth of a marine-derived actinobacterium Streptomyces qinglanensis 213DD-006. Among them, 1, 4, 7, and 9 were new compounds. Their planar structures were determined by spectroscopic methods (HRMS, 1D, and 2D NMR), and the absolute configuration was established by biosynthesis consideration and electronic-circular-dichroism (ECD) calculations. All the isolated compounds were screened for their cytotoxicity against six solid and seven blood cancer cell lines. Compounds 4-6 and 8 showed a moderate activity against all of the tested solid cell lines, with GI50 values ranging from 1.97 to 3.46 µM.
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No pos
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No neg
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Retriever2268
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Disordered eating and insulin restriction in youths receiving intensified insulin treatment: Results from a nationwide population-based study.
OBJECTIVE
This Germany-wide population-based study sought to estimate the prevalence of disordered eating and insulin restriction (IR) among 819 youths aged 11-21 years with early-onset type 1 diabetes (T1D) and a disease duration of at least 10 years.
METHODS
All respondents answered the five-item SCOFF screening questionnaire for eating disorders (EDs) and reported on the frequency of IR and clinical outcomes. Screening for disordered eating was positive when more than two SCOFF items were answered affirmatively. Frequent IR was defined as IR occurring more than five times per week.
RESULTS
A total of 28.2%/9.2% of the female/male patients were SCOFF-positive without IR and 4.2%/5.3% reported frequent IR but were SCOFF-negative; 2.7%/1.9% screened positive for both disordered eating and IR. Patients with disordered eating, frequent IR, or both showed significantly worse glycemic control and partly more inpatient-treated diabetic ketoacidoses than patients who screened negative.
DISCUSSION
Approximately one in three female and one in six male patients with early-onset long-duration T1D reported disordered eating and/or frequent IR. Because of their association with worse outcomes, both disordered eating and IR should be considered in T1D care irrespective of sex, age at onset, and diabetes duration.
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No pos
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No neg
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Retriever2269
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Toxicity of Myristica fagrans seed compounds against Blattella germanica (Dictyoptera: Blattellidae).
The insecticidal constituents of hexane-soluble fraction from a methanolic extract of the seeds from Myristica fragrans (Myristicaceae) against adult females of Blattella germanica (L.) (Dictyoptera: Blattellidae) were analyzed by gas chromatography and gas chromatography-mass spectrometry. The insecticidal activity of 13 Myristica seed compounds against female B. germanica was examined by using the filter-paper contact toxicity and vapor phase toxicity bioassays. Results were compared with those of the other 23 known compounds of Myristica seed and currently used insecticides: dichlorvos, deltamethrin, permethrin, and propoxur. In contact toxicity tests using female B. germanica, (IS)-(-) -beta-pinene (0.06 mg/cm2) was the most toxic insecticide, based on 24-h LD50 values. The insecticidal activity of this compound was comparable with that of permethrin (0.05 mg/cm2). (1R)-(+) -Camphor, (1S)-(-) -camphor, dipentene, (1R)-(+) -3-pinene, and (+)-alpha-terpineol (0.10-0.14 mg/cm2) were more toxic than propoxur (0.19 mg/cm2). (E)-Sabinene hydrate and propoxur were almost equitoxic. Potent insecticidal activity also was observed with (R)-(+) -citronellal, (S)-(-) -citronellal, (R)-(-) -alpha-phellandrene, (1S)-(-) -alpha-pinene, (1R)-(+) -alpha-pinene, and safrole (0.27-0.48 mg/cm2). In vapor phase toxicity tests, the compounds tested were effective in closed but not in open containers. These results indicate that the effect of these compounds was largely a result of action in the vapor phase. Myristica seed compounds described merit further study as potential insecticides or as leads for the control of cockroaches.
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No pos
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No neg
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Retriever2270
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Immunohistochemical studies of fetal trophoblast and maternal decidua in hydatidiform mole and choriocarcinoma.
Immunohistochemical techniques have been used to investigate the expression of fetal trophoblast antigens and the maternal leucocytic response in molar pregnancy and choriocarcinoma. The antigenic phenotype of morphologically defined trophoblast populations in complete, partial and invasive moles was analogous to that in normal pregnancy. All trophoblast phenotypes described in normal pregnancy were also identified in choriocarcinoma, suggesting that extensive differentiation into heterogeneous subgroups occurs in malignant trophoblast. The maternal leucocytic infiltrate in molar pregnancy consisted of T lymphocytes and class II MHC-positive macrophages. CD2-positive, CD3-negative lymphocytes were identified in molar decidua but not in uterine tissue in choriocarcinoma. Similarly, endometrial granulocytes were present in molar decidua but not in choriocarcinoma; these cells were associated with decidualization rather than with fetal trophoblast.
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No pos
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No neg
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Retriever2271
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A microfluidic system for dynamic yeast cell imaging.
The investigation of cellular processes and gene regulatory networks within living cells requires the development of improved technology for dynamic, single cell imaging. Here, we demonstrate a microfluidic system capable of mechanical trapping of yeast cells with continuous flow and flow switching capability during time-lapse high magnification fluorescence imaging. The novel functionality of the system was validated by observing the response of pheromone-induced expression of GFP in Saccharomyces cerevisiae.
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No pos
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No neg
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Retriever2272
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Anaerobic treatment of pinkwater in a fluidized bed reactor containing GAC.
Pinkwater is generated during the handling and demilitarization of conventional explosives. This listed hazardous waste contains dissolved trinitrotoluene (TNT) and cyclo trimethylene trinitramine (RDX), as well as some by-products. It represents the largest quantity of hazardous waste generated by the operations support command, and its treatment produces a by-product hazardous waste--spent granular activated carbon (GAC). Anaerobic treatment in a fluidized bed reactor (FBR) containing GAC is an emerging technology for organic compounds resistant to aerobic biological treatment. Bench scale batch studies using an anaerobic consortium of bacteria fed ethanol as the sole electron donor demonstrated the transformation of TNT to triaminotoluene (TAT), which then degrades to undetectable end products. RDX is sequentially degraded to nitroso-, dinitroso-, trinitroso- and hydroxylaminodinitroso-RDX before the triazine ring is presumably cleaved, forming methanol and formaldehyde as major end products. The bacterial members of the anaerobic consortia are typically found in sludge digesters at municipal or industrial wastewater treatment plants. The results of a pilot scale evaluation of this process that was conducted at McAlester Army Ammunition Plant (MCAAP, OK) over a 1 year period are reported in this paper. The pilot test experienced wide fluctuations in influent concentrations, representative of true field conditions. The FBR was a 20 in. (51 cm) diameter column with an overall height of 15 ft (4.9 m) and a bed of GAC occupying 11 ft (3.4m). Water was recirculated through the column continuously at 30 gpm (114 l/min) to keep the GAC fluidized, and pinkwater for treatment was pumped into the recirculation line. Several flowrates were evaluated to determine the proper mass loading rate (mass of TNT and RDX per reactor volume per time, kg/m(3) per day) which the reactor could handle while meeting the discharge limitations. Based on the tests performed, a 1 gpm (3.785 l/min) rate in the 188 gal (710 l) volume of the fluidized GAC bed was determined to consistently meet the discharge requirements. This information was used to develop a cost estimate for a system capable of treating the total effluent currently produced at MCAAP. The cost of installing and operating this system was compared to the cost of GAC adsorption for MCAAP at current pinkwater generation rates. The GAC-FBR system had an annual operating cost of approximately US$ 19K, compared to US$ 71 K annually for GAC adsorption. When including the amortization of the capital equipment required for the GAC-FBR, the payback period for installation of this new process was estimated at 3.7 years.
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No pos
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No neg
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Retriever2273
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Comparison of Neuroform Atlas Stent-Assisted Coiling and Coiling Alone in Ruptured Intracranial Aneurysms: A Propensity Score Matching Analysis.
BACKGROUND
Although Neuroform Atlas stent is commonly used in stent-assisted coiling (SAC) to treat ruptured intracranial aneurysms (RIA), its safety and efficacy remain controversial.
OBJECTIVE
To assess the safety and efficacy of SAC using Neuroform Atlas for treating RIA compared with coiling alone by performing a propensity score matching analysis.
METHODS
RIA treated with coiling alone and SAC between January 2017 and May 2021 were retrospectively reviewed. Demographics, periprocedural complication rates, angiographic outcomes, and clinical outcomes of the SAC using Neuroform Atlas group and the coiling-alone group were analyzed with 1:1 propensity score matching.
RESULTS
A total of 375 aneurysms were enrolled, and 274 (63.1%) aneurysms were treated with coiling alone. In total, 101 (26.9%) aneurysms were treated with SAC, and Neuroform Atlas stent was used in 71 aneurysms. In propensity score matching, the SAC using Neuroform Atlas group showed higher incidence of complete occlusion (69.0% vs 56.3%, P = .029), lower rate of recanalization (11.3% vs 25.4%, P = .011), and lesser need for retreatment (7.0% vs 16.9%, P = .016) compared with the coiling-alone group. However, there were no significant differences in periprocedural complications such as intraprocedural thrombosis or postprocedural cerebral infarct between the 2 groups.
CONCLUSION
The use of Neuroform Atlas is safe and effective for SAC in RIA with comparable procedure-related complication rates but better angiographic outcome in comparison with coiling alone.
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No pos
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No neg
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Retriever2274
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Some quantifier functions from weighting functions with constant value of orness.
The quantifier-guided aggregation is used for aggregating the multiple-criteria input. Therefore, the selection of appropriate quantifiers is crucial in multicriteria aggregation since the weights for the aggregation are generated from the selected quantifier. Since Yager proposed a method for obtaining the ordered weighted averaging (OWA) vector via the three relative quantifiers used for the quantifier-guided aggregation, limited efforts have been devoted to developing new quantifiers that are suitable for use in multicriteria aggregation. In this correspondence, we propose some new quantifier functions that are based on the weighting functions characterized by showing a constant value of orness independent of the number of criteria aggregated. The proposed regular increasing monotone and regular decreasing monotone quantifiers produce the same orness as the weighting functions from which each quantifier function originates. Further, the quantifier orness rapidly converges into the value of orness of the weighting functions having a constant value of orness. This result indicates that a quantifier-guided OWA aggregation will result in a similar aggregate in case the number of criteria is not too small.
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No pos
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No neg
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Retriever2275
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Acetylated HOXB13 Regulated Super Enhancer Genes Define Therapeutic Vulnerabilities of Castration-Resistant Prostate Cancer.
PURPOSE
Androgen receptor (AR) antagonism is exacerbated by HOXB13 in castration-resistant prostate cancers (CRPC). However, it is unclear when and how HOXB13 primes CRPCs for AR antagonism. By mass-spectrometry analysis of CRPC extract, we uncovered a novel lysine 13 (K13) acetylation in HOXB13 mediated by CBP/p300. To determine whether acetylated K13-HOXB13 is a clinical biomarker of CRPC development, we characterized its role in prostate cancer biology.
EXPERIMENTAL DESIGN
We identified tumor-specific acK13-HOXB13 signal enriched super enhancer (SE)-regulated targets. We analyzed the effect of loss of HOXB13K13-acetylation on chromatin binding, SE proximal target gene expression, self-renewal, enzalutamide sensitivity, and CRPC tumor growth by employing isogenic parental and HOXB13K13A mutants. Finally, using primary human prostate organoids, we evaluated whether inhibiting an acK13-HOXB13 target, ACK1, with a selective inhibitor (R)-9b is superior to AR antagonists in inhibiting CRPC growth.
RESULTS
acK13-HOXB13 promotes increased expression of lineage (AR, HOXB13), prostate cancer diagnostic (FOLH1), CRPC-promoting (ACK1), and angiogenesis (VEGFA, Angiopoietins) genes early in prostate cancer development by establishing tumor-specific SEs. acK13-HOXB13 recruitment to key SE-regulated targets is insensitive to enzalutamide. ACK1 expression is significantly reduced in the loss of function HOXB13K13A mutant CRPCs. Consequently, HOXB13K13A mutants display reduced self-renewal, increased sensitivity to enzalutamide, and impaired xenograft tumor growth. Primary human prostate tumor organoids expressing HOXB13 are significantly resistant to AR antagonists but sensitive to (R)-9b.
CONCLUSIONS
In summary, acetylated HOXB13 is a biomarker of clinically significant prostate cancer. Importantly, PSMA-targeting agents and (R)-9b could be new therapeutic modalities to target HOXB13-ACK1 axis regulated prostate cancers.
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No pos
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No neg
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Retriever2276
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Improved foot management of people with diabetes by primary healthcare nurses in Auckland, New Zealand.
AIMS
Evaluate trends in foot examinations for people with diabetes by primary healthcare nurses between 2006-2008 and 2016 in Auckland, New Zealand.
METHODS
All primary care nurses in 2006-2008 and 2016 were identified and 26% and 24% were randomly sampled and surveyed, respectively. Nurse participants completed a self-administered questionnaire and telephone interview about the care provided for people with diabetes.
RESULTS
Significantly more patients consulted by practice nurses received foot examinations in 2016 (58%) compared with 2006-2008 (36%), and foot-care education (66% versus 26%). Of the 43% of patients who had no foot examination in 2016, 23% had no previous examination documented. Significantly more nurses in 2016 than in 2006-2008 self-reported routinely examining patients' feet (45% versus 31%) and giving foot-care education (28% versus 13%). These practices were associated with nurses undertaking >5 hours of diabetes education within the past five years.
CONCLUSIONS
Practice nurses have significantly expanded their role in managing people with diabetes over the last decade by increasing the number of foot examinations and providing recommended foot-care education. Improved management was associated with nurses attending diabetes education in the past five years. Gaps were identified in conducting the recommended number of foot examinations, categorising patients' risk of foot disease and recording previous examinations.
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No pos
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No neg
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Retriever2277
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L-arginine infusion during resuscitation for hemorrhagic shock: impact and mechanism.
BACKGROUND
Our previous work showed a survival advantage with L-arginine (L-Arg) pretreatment in a swine model of severe hemorrhagic shock. This study was designed to evaluating whether the benefit is sustained when L-Arg is given during resuscitation and whether the mechanism is mediated by enzymatic activation of nitric oxide (NO) synthesis.
METHODS
Adult rats (n = 30) underwent 40% blood volume loss and were resuscitated with saline (3 shed blood volume). Animals were divided into five treatment groups of six animals each: (1) Sham, (2) Control (resuscitation alone), (3) L-Arg (300 mg/kg)with resuscitation, (4) L-Arg + L-nitroarginine methyl ester pretreatment, and (5) D-arginine (300 mg/kg) with resuscitation.Animals were observed for 240 minutes postresuscitation or until death. Hemodynamic, metabolic, histologic, and survival outcomes were measured.
RESULTS
Administration of L-Arg after hemorrhage and before resuscitation significantly improved outcomes, relative to the control group.The L-Arg infusion improved terminal arterial pressures, lowered lactate, improved small bowel histologic signs of reperfusion injury, and increased survival (p < 0.05). Endpoints of the L-Arg group were similar to the Sham group. The benefits of L-Arg infusion were abolished or attenuated when animals were pretreated with L-nitro arginine methyl ester and potentiated with D-arginine, suggesting a NO-specific mechanism of L-Arg. Finally, severe shock and resuscitation injury significantly elevated circulating asymmetric dimethylarginine levels, which are potent competitive inhibitors of NO synthetase.
CONCLUSION
L-Arg infusion during resuscitation offers a significant functional, metabolic, and survival benefit after severe hemorrhagic shock.The mechanism seems to be by activation of NO synthesis with its attendant benefits to local perfusion and inflammation after global reperfusion.
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No pos
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No neg
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Retriever2278
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In transgenic mice the introduced functional T cell receptor beta gene prevents expression of endogenous beta genes.
Transgenic mice were constructed with a functional T cell receptor beta gene. Transcription of the introduced gene is largely confined to T cells, but low levels of transcripts are also seen in B cells and in other tissues. Serological analyses show that most, if not all, of the T lymphocytes express the transgenic beta chain on the cell surface and lack beta chains encoded by endogenous beta genes. Molecular genetic analyses of uncloned and cloned T lymphocytes demonstrate that rearrangement of endogenous beta genes is incomplete. Partial D beta 1-J beta 1 rearrangements are found preferentially, while complete VDJ rearrangements are not seen. These findings show that expression of the transgene regulates the rearrangement of endogenous beta genes. Although the alpha beta T cell receptors of the transgenic mice are homogeneous with respect to the beta chain, they are fully functional, at least in a variety of allogeneic responses.
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No pos
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No neg
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Retriever2279
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Antioxidant constituents of radish sprout (Kaiware-daikon), Raphanus sativus L.
Methanol extracts of 11 kinds of commonly available vegetables were examined for hydroxyl radical scavenging potency using the bleomycin-Fe method. In this method, the iron ion and bleomycin in water form hydroxyl radicals, and the scavenging activity is monitored by the modified thiobarbituric acid method. All extracts showed scavenging capacity, even though the activity of some of them was lower than that of l-ascorbic acid. Those vegetables were classified into three groups according to their activity, groups showing strong activity, moderate activity, and weak activity, as compared to the activity of l-ascorbic acid at the same concentration. Among them, the methanol extract of radish sprout (Japanese name "kaiware-daikon") exhibited the highest potency (1.8 times as l-ascorbic acid). Then, we investigated the constituents of the methanol extract of radish sprout and the contribution to the overall activity of each compound by examining their activity. As the result, several kinds of sinapinic acid esters and flavonoids were isolated with high radical scavenging potency, which must contribute substantially to the activity.
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No pos
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No neg
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Retriever2280
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In Situ Characterization of Boehmite Particles in Water Using Liquid SEM.
In situ imaging and elemental analysis of boehmite (AlOOH) particles in water is realized using the System for Analysis at the Liquid Vacuum Interface (SALVI) and Scanning Electron Microscopy (SEM). This paper describes the method and key steps in integrating the vacuum compatible SAVLI to SEM and obtaining secondary electron (SE) images of particles in liquid in high vacuum. Energy dispersive x-ray spectroscopy (EDX) is used to obtain elemental analysis of particles in liquid and control samples including deionized (DI) water only and an empty channel as well. Synthesized boehmite (AlOOH) particles suspended in liquid are used as a model in the liquid SEM illustration. The results demonstrate that the particles can be imaged in the SE mode with good resolution (i.e., 400 nm). The AlOOH EDX spectrum shows significant signal from the aluminum (Al) when compared with the DI water and the empty channel control. In situ liquid SEM is a powerful technique to study particles in liquid with many exciting applications. This procedure aims to provide technical know-how in order to conduct liquid SEM imaging and EDX analysis using SALVI and to reduce potential pitfalls when using this approach.
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No pos
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No neg
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Retriever2281
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Posterior Hyaloidotomy by Nd:YAG Laser Application in a Patient with Postpartum Depression Caused by Valsalva Retinopathy.
PURPOSE
The aim of this report is to present a case of premacular hemorrhage in a 37-week pregnant woman with concurrent presence of postpartum depression secondary to her ocular disease.
METHODS
A 27-year-old woman in her 37th week of pregnancy presented with Valsalva retinopathy, which occurred in her left eye secondary to severe coughing. Her visual acuity was reduced to perception of hand motions, and she was agitated because of the loss of vision. The patient, who gave birth by cesarean section, was admitted for control examination 2 weeks after birth. No change was observed in premacular hemorrhage in control examination. However, the patient's relatives stated that the patient was very agitated and disinterested in her baby. For this reason, the patient was referred to the psychiatry clinic, and she was diagnosed with postpartum depression. The anatomical location of the premacular hemorrhage was determined by spectral domain optical coherence tomography.
RESULTS
Neodymium yttrium aluminum garnet (Nd:YAG) laser hyaloidotomy was performed to her left eye on the same day. Rapid release of premacular hemorrhage into the vitreous cavity was observed immediately after Nd:YAG laser application. Two days after the application, the patient's visual acuity had improved to 20/20. The clinical improvement positively impacted on the patient's mood.
CONCLUSION
In pregnant patients suffering from Valsalva retinopathy during the postpartum period, posterior hyaloidotomy by Nd:YAG laser can be implemented in terms of the patients' own and their babies' physical and mental health.
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No pos
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No neg
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Retriever2282
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Early Application of Palbociclib Plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer: A Better Choice Based on Data From the Chinese Population.
Background: Palbociclib is the most widely used cyclin-dependent kinase 4/6 inhibitor in China, but its early application efficacy on Chinese metastatic breast cancer (MBC) patients was reported deficiently. Methods: Between February 2019 to December 2021, 95 female hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) patients with MBC received palbociclib combined with AI or fulvestrant were retrospectively analyzed in our center. The primary outcome was progression-free survival (PFS). The objective response rate and clinical benefit rate (CBR) were evaluated. Results: The median follow-up period was 15 months (range from 2 to 37). Palbociclib performed superiorly when applicated in first-and-second line therapy than in later lines (P = .002). Palbociclib combined with AI or fulvestrant had a median PFS of 34 months (95% confidence interval [CI] = 6.87-61.13) and 12 months (95%CI = 7.76-16.24), respectively. Univariate subgroup analysis showed that the previous history of salvage chemotherapy (P = .015) and the presence of liver metastases (P < .001) significantly affected the efficacy of palbociclib. Despite the existence of liver metastases and primary endocrine resistance, which are two independent predictors of poor prognosis, early application of palbociclib in advanced stage can bring further benefits to these two groups of patients, rather than choosing salvage chemotherapy in the first place. Conclusion: Palbociclib combined with endocrine therapy has a favorable efficacy and acceptable toxicity in HR+/HER2- Chinese MBC patients. Better performance can be seen when palbociclib was applicated in the early stage.
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No pos
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No neg
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Retriever2283
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Cell cycle modulation of gene targeting by a triple helix-forming oligonucleotide.
Successful gene-targeting reagents must be functional under physiological conditions and must bind chromosomal target sequences embedded in chromatin. Triple helix-forming oligonucleotides (TFOs) recognize and bind specific sequences via the major groove of duplex DNA and may have potential for gene targeting in vivo. We have constructed chemically modified, psoralen-linked TFOs that mediate site-specific mutagenesis of a chromosomal gene in living cells. Here we show that targeting efficiency is sensitive to the biology of the cell, specifically, cell cycle status. Targeted mutagenesis was variable across the cycle with the greatest activity in S phase. This was the result of differential TFO binding as measured by cross-link formation. Targeted cross-linking was low in quiescent cells but substantially enhanced in S phase cells with adducts in approximately 20-30% of target sequences. 75-80% of adducts were repaired faithfully, whereas the remaining adducts were converted into mutations (>5% mutation frequency). Clones with mutations could be recovered by direct screening of colonies chosen at random. These results demonstrate high frequency target binding and target mutagenesis by TFOs in living cells. Successful protocols for TFO-mediated manipulation of chromosomal sequences are likely to reflect a combination of appropriate oligonucleotide chemistry and manipulation of the cell biology.
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No pos
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No neg
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Retriever2284
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Analysis of HTT CAG repeat expansion in Italian patients with amyotrophic lateral sclerosis.
HTT full-penetrance pathogenic repeat expansions, the genetic cause of Huntington's disease (HD), have been recently reported in a minority of frontotemporal dementia/amyotrophic lateral sclerosis (ALS) patients (0.13%). We analyzed HTT CAG repeats in an Italian cohort of ALS patients (n = 467) by repeat-primed polymerase chain reaction. One patient harbored two expanded alleles in the HTT gene (42 and 37 CAG repeats). The absence of HD typical symptoms and the clinical picture consistent with ALS, corroborated by the diagnostic assessment, apparently excluded a misdiagnosis of HD.
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No pos
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No neg
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Retriever2285
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The unsaturated acyclic nucleoside analogues bearing a sterically constrained (Z)-4'-benzamido-2'-butenyl moiety: Synthesis, X-ray crystal structure study, cytostatic and antiviral activity evaluations.
A series of the novel acyclic unsaturated pyrimidine (1-12) and adenine (13) nucleoside analogues bearing conformationally restricted (Z)-2'-butenyl moiety were synthesized and evaluated for their antiviral and cytostatic activity potency against malignant tumor cell lines and normal human fibroblast (WI38). The N-1 and/or N-3 acyclic side chain substitution in pyrimidine ring in N-3 substituted 5-trifluoromethyluracil derivative (11), N-1, N-3 disubstituted 5-fluorouracil derivative (12) and adenine derivative (13) was deduced from their (1)H and (13)C NMR spectra and confirmed by single crystal X-ray structure analysis. The X-ray crystal structure analysis 11-13 revealed also supramolecular self-assemblies, in which infinite chains or dimers built two- and three-dimensional networks. The results of the in vitro cytostatic activity evaluations of 1-13 indicate that the majority of the compounds tested exhibited a non-specific and moderate antiproliferative effect at the highest concentration (100 microM). Of all evaluated compounds on the cell lines tested only the N-1 4''-fluoro-substituted-benzamide uracil derivative (7) showed rather marked and selective inhibitory activity against the growth of MCF-7 cells at a concentration of 2.7 microM and no cytotoxic effect on normal fibroblasts WI38. This compound can be therefore considered as a potential antitumor lead compound for further synthetic structure modification.
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No pos
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No neg
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Retriever2286
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Clonal Lineage Analysis of Shigella flexneri Isolates Circulating in Ahvaz, Iran.
BACKGROUND
Shigellosis is a significant public health challenge particularly in developing countries, and the spread of antibiotic resistance genes through integron structures has become an important problem in the treatment of Shigellosis. The aim of this study was to investigate the genetic association of Shigella flexneri antibiotic resistant clones collected from Ahvaz between 2013 and 2015 by pulse field gel electrophoresis (PFGE) method.
METHODS
A total of 45 S. flexneri isolates, which were resistant to ampicillin and cotrimoxazole, were obtained from patients with Shigellosis referred to Ahvaz hospitals during 2013 - 2015. PCR was performed to evaluate the frequency of Sul1, int1, blaOXA, and int2 genes. In addition, pulse field gel electrophoresis method was used to investigate the genetic relationship between 40 S. flexneri isolates.
RESULTS
PCR results showed that the highest frequency was related to the sul1 gene with 80% (36 isolates) and the lowest frequency was related to class 2 integron with 15.5% (7 isolates); 31.11% (14 isolates) of the isolates were sul1 and int1. Also, 13.33% (6 isolates) had blaOXA and int1 genes, simultaneously. But none of the isolates had class 1 integrons and class 2 integrons at the same time. PFGE results showed 25 different pulsotype patterns, of which 16 isolates had their own unique pattern and were divided into 16 pulsotypes, and 27 isolates were divided into 9 pulsotypes.
CONCLUSIONS
int2 and sul1 resistance genes had an upward trend from 2013 to 2015 and the results of PFGE indicated a different origin of S. flexneri clones.
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No pos
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No neg
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Retriever2287
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Hepatozoon caimani Carini, 1909 (Adeleina: Hepatozoidae) in wild population of Caiman yacare Daudin, 1801 (Crocodylia: Alligatoridae), Pantanal, Brazil.
Previous studies showed infections of Hepatozoon caimani in wild populations of caimans in wide regions from Brazil; some of those demonstrated that trophic chain are linked to natural infections through paratenic hosts or by the direct ingestion of vectors. These studies life cycle of H. caimani contributed inestimably to the knowledge of transmission routes, yet but lack enhancement tools for better detail of parasite. This study reports the forms in the blood and tissues, and also partial molecular characterization of the H. caimani following part of the 18S rRNA region. In the southern Pantanal, there were sampling 39 adult caimans (Caiman yacare), where 31 (79.5%) were parasitized by H. caimani. Free gametocytes had an average intensity of 19.6% and intraerythrocytic forms 7.42%, in the blood smears. In stained smears of the liver and lungs of naturally infected caimans which were examined, monozoic and dizoic cysts were found in these tissues, generally next to the vessels. In the histopathology, meronts were observed in the wall of vessels from liver and kidney ducts. Blood samples were forwarded to PCR process and produced amplicons with about 600 and 900 bp, respectively, for the primers HEPF300/HEP900 and HEMO1/HEMO2. This was the first report of molecular confirmation of Hepatozoon in populations of naturally infected caimans of morphological detail of the gametocytes in scanning electron microscopy and histology of merogony in livers and kidneys of C. yacare.
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No pos
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No neg
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Retriever2288
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The development of oral vaccines against parasitic diseases utilizing live attenuated Salmonella.
Genetically defined, live attenuated Salmonella vaccines are proving useful both as oral vaccines against salmonellosis and for the development of multivalent vaccines based on the expression of heterologous antigens in such strains. Several candidate attenuated S. typhi strains are at present being evaluated as new single dose oral typhoid vaccines in human volunteers. The emergence of such a vaccine will facilitate the development of multivalent vaccines for humans. Many antigens from different infectious organisms have been expressed in attenuated Salmonella. A focus of this work has been on developing vaccines against parasitic diseases. This review will summarize the efforts that have been made in this area.
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No pos
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No neg
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Retriever2289
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Jasmonic acid effect on the fatty acid and terpenoid indole alkaloid accumulation in cell suspension cultures of Catharanthus roseus.
The stress response after jasmonic acid (JA) treatment was studied in cell suspension cultures of Catharanthus roseus. The effect of JA on the primary and secondary metabolism was based on changes in profiles of fatty acids (FA) and terpenoid indole alkaloids (TIA). According to multivariate data analyses (MVDA), three major time events were observed and characterized according to the variations of specific FA and TIA: after 0-30 min of induction FA such as C18:1, C20:0, C22:0 and C24:0 were highly induced by JA; 90-360 min after treatment was characterized by variations of C14:0 and C15:0; and 1440 min after induction JA had the largest effect on both group of metabolites were C18:1, C18:2, C18:3, C16:0, C20:0, C22:0, C24:0, catharanthine, tabersonine-like 1, serpentine, tabersonine and ajmalicine-like had the most significant variations. These results unambiguously demonstrate the profound effect of JA particularly on the accumulation of its own precursor, C18:3 and the accumulation of TIA, which can be considered as late stress response events to JA since they occurred only after 1440 min. These observations show that the early events in the JA response do not involve the de novo biosynthesis of neither its own precursor nor TIA, but is due to an already present biochemical system.
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No pos
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No neg
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Retriever2290
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The Effect of Antibiotic Treatment of Early Childhood Shigellosis on Long-Term Prevalence of Attention Deficit/Hyperactivity Disorder.
It has recently been shown that children with early shigellosis are at increased risk of attention deficit/hyperactivity disorder (ADHD). This study aimed to evaluate the association between antibiotic treatment of shigellosis with long-term ADHD rates. A retrospective cohort study was conducted that included all the Leumit Health Services (LHS) enrollees aged 5-18 years between 2000-2018 with a documented Shigella-positive gastroenteritis before the age of 3 years. Of the 5176 children who were positive for Shigella gastroenteritis before the age of 3 years, 972 (18.8%) were treated with antibiotics early (<5 days), 250 (4.8%) were treated late (≥5 days), and 3954 children (76.4%) were not prescribed antibiotics. Late antibiotic treatment was associated with significantly increased rates of ADHD (adjusted OR = 1.61; 95% CI, 1.1-2.3). Early treatment with antibiotics was not associated with increased ADHD rates (adjusted OR = 1.02; 95% CI, 0.8-1.3). In conclusion, late antibiotic treatment of early childhood shigellosis was associated with increased rates of ADHD.
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No pos
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No neg
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Retriever2291
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Angiotensin-(1-7) binding at angiotensin II receptors in the rat brain.
Angiotensin-(1-7) (Ang-(1-7)) is reported to be equipotent with angiotensin II (AII) in producing some central biological effects but the receptors responsible for these actions have not been defined. Three classes of receptor have been proposed: AT1, AT2, and a putative Ang-(1-7) selective receptor. This study specifically evaluates Ang-(1-7) competition at AII binding sites (AT1 and AT2) in the rat brain. 125I Sar1 Ile8 AII (269-312 pM) was used to conduct receptor autoradiographic binding assays in brain sections. Competition with Ile5 AII and Val5 AII was similar at nuclei in which either AT1 or AT2 receptor subtypes predominate (Ki = 11-18 nM). Ang-(1-7) competed 150-fold less effectively than native AII at AT1 predominant brain nuclei (Ki = 2.4 microM). At brain regions where AT2 receptors predominate, Ang-(1-7) showed a very low affinity (Ki = 104 microM) for the majority of the 125I Sar1 Ile8 AII binding sites (AT2). A small proportion of 125I Sar1 Ile8 AII binding sites showed an affinity of 2.0 microM, presumably AT1 receptors present in those brain regions. For biological responses where Ang-(1-7) is reported to be equipotent with AII, it is unlikely that these actions are mediated by the widely distributed AT1 or AT2 receptor subtypes which recognize 125I Sar1 Ile8 AII.
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No pos
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No neg
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Retriever2292
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Dysphagia lusoria associated with an esophageal carcinoma.
A patient with dysphagia lusoria associated with an esophageal carcinoma is reported. A review of the literature of this unusual condition is presented.
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No pos
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No neg
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Retriever2293
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Non-ST elevation myocardial infarction related to total coronary artery occlusion - prevalence and patient characteristics.
INTRODUCTION
Acute coronary occlusion (ACO) may also present as non-ST elevation myocardial infarction (NSTEMI) and thus veil the real threat.
AIM
Based on combined analysis of electrocardiography and echocardiography findings, we aimed to describe profile of NSTEMI patients at increased risk of ACO.
MATERIAL AND METHODS
It was a retrospective study that included patients referred for cardiac catheterisation due to NSTEMI. Patients were selected into the study in two different time frames. Firstly, all consecutive NSTEMI patients were enrolled in a 12-month period to detect the prevalence of ACO (prevalence group). Secondly, all NSTEMI patients with ACO hospitalized in the previous 5 years were also enrolled (NSTEMI-ACO group). All patients had 12-lead electrocardiogram (ECG) and the transthoracic echocardiography (TTE) performed before the cardiac catheterisation.
RESULTS
Fifty-three consecutive patients (37 males) were enrolled into the prevalence group in a 12-month period. Ten (19%) of them were diagnosed with ACO. Thirty-four consecutive patients were enrolled into the NSTEMI-ACO group. Non-ST elevation myocardial infarction patients with ACO were younger as compared to NSTEMI patients without ACO. Non-ST elevation myocardial infarction patients with ACO were less likely to have anterior wall ischaemia as detected by ECG, which was not reflected by TTE results. Combined assessment of ischaemia by ECG and impaired contractility by TTE did not reveal any significant differences between NSTEMI patients with or without ACO.
CONCLUSIONS
The identification of NSTEMI patients with ACO is challenging. Therefore, the utmost caution should be paid to prevent delay of coronary angiography in NSTEMI patients who have increased risk of ACO.
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No pos
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No neg
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Retriever2294
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A review of studies of psychiatric factors in Crohn's disease: etiologic implications.
Researchers have recently challenged long-held concepts of psychological origins to inflammatory bowel disease, in particular with ulcerative colitis. The purpose of this paper is to review published studies on psychiatric factors in Crohn's disease to determine whether available evidence points to the absence or presence of a significant relationship between Crohn's disease and stressful life events or psychiatric symptoms or disorders. Twelve articles with > or = 10 subjects on which statistical data were reported from standardized instruments of measure were found. Most reported a significant association between Crohn's disease and psychiatric factors. Many of the investigative groups reporting such an association in Crohn's disease had also studied ulcerative colitis and failed to find a similar association in that disease. Published data indicate that Crohn's disease, unlike ulcerative colitis, may be statistically associated with lifetime psychiatric disorders. This association appears to be more modest than in irritable bowel syndrome, in which far higher rates of psychiatric disorders are reported than in Crohn's disease.
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No pos
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No neg
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Retriever2295
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The recurrent coronary prevention project. Some preliminary findings.
The Recurrent Coronary Prevention Project (RCPP) was established as a 5-year clinical trial to examine two basic questions: --1. Can the recurrence rate of post-coronary subjects be substantially reduced over a 5-year period by means of a programme of behavioural change, in comparison with treatment by cardiologists focussing on medication, diet, exercise and cardiovascular issues, and with subjects who only receive regular care from their own physician? 2. Can the Type A behaviour pattern (TABP) be changed and do such changes correspond to reduced recurrences of coronary heart disease (CHD) over a 5 year period? To answer these questions, four major treatment groups are currently being compared: --1. A small group treatment programme (Section I) led by cardiologists emphasizing adherence to medication, diet and exercise, and giving cardiovascular and cardiological information. 2. A behavioural change treatment programme (Section II) based primarily on a cognitive social learning model and attempting to alter TABP. 3. A control group of subjects assessed annually and receiving private medical care from their own physicians. 4. A dropout comparison group composed of subjects voluntarily discontinuing participation in groups led by cardiologists or in behavioural change groups. Results to date show a significantly reduced rate of recurrence for subjects in the behavioural change group, compared to those in the groups led by cardiologists as well as control and dropout groups. These significantly lower recurrence rates are accompanied by data suggesting that subjects in the behavioural change programme are also altering their TABP as measured by both behavioural questionnaires and videotaped Type A structured interviews. Clinical impressions suggest that treatment programmes to alter TABP should consider the primary importance of the personal meaning of the TABP and other behaviours to the individual concerned, particularly how basic underlying beliefs set the stage for the TABP. The central role of hostility as a pervasive orientation towards self and others is emphasized, as are issues of excessive controllability related to extreme competitiveness and hyper-arousal. The multiple roles of group leaders, especially as social models for coping, and the impact of the small groups settings, is also discussed.
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No pos
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No neg
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Retriever2296
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Surgical management of palatal teratoma (epignathus) with the use of virtual reconstruction and 3D models: a case report and literature review.
Epignathus is a rare congenital orofacial teratoma that arises from the sphenoid region of the palate or the pharynx. It occurs in approximately 1:35,000 to 1:200,000 live births representing 2% to 9% of all teratomas. We present the case of a newborn of 39.4 weeks of gestation with a tumor that occupied the entire oral cavity. The patient was delivered by cesarean section. Oral resection was managed by pediatric surgery. Plastic surgery used virtual 3-dimensional models to establish the extension, and depth of the tumor. Bloc resection and reconstruction of the epignathus were performed. The mass was diagnosed as a mature teratoma associated with cleft lip and palate, nasoethmoidal meningocele that conditions hypertelorism, and a pseudomacrostoma. Tridimensional technology was applied to plan the surgical intervention. It contributed to a better understanding of the relationships between the tumor and the adjacent structures. This optimized the surgical approach and outcome.
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No pos
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No neg
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Retriever2297
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Deconvolution of pigment and physiologically related photochemical reflectance index variability at the canopy scale over an entire growing season.
The sensitivity of the photochemical reflectance index (PRI) to leaf pigmentation and its impacts on its potential as a proxy for light-use efficiency (LUE) have recently been shown to be problematic at the leaf scale. Most leaf-to-leaf and seasonal variability can be explained by such a confounding effect. This study relies on the analysis of PRI light curves that were generated at the canopy scale under natural conditions to derive a precise deconvolution of pigment-related and physiologically related variability in the PRI. These sources of variability were explained by measured or estimated physiologically relevant variables, such as soil water content, that can be used as indicators of water availability and canopy chlorophyll content. The PRI mainly reflected the variability in the pigment content of the canopy. However, the corrected PRI, which was obtained by subtracting the pigment-related seasonal variability from the PRI measurement, was highly correlated with the upscaled LUE measurements. Moreover, the sensitivity of the PRI to the leaf pigment content may mask the PRI versus LUE relationship or result in an artificial relationship that reflects the relationship of chlorophyll versus LUE, depending on the species phenology.
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No pos
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No neg
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Retriever2298
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Cyclotron production of ⁹⁹mTc: recycling of enriched ¹⁰⁰Mo metal targets.
There is growing interest in the large scale cyclotron production of (99m)Tc via the (100)Mo(p,2n)(99m)Tc reaction. While the use and recycling of cyclotron-irradiated enriched molybdenum targets has been reported previously in the context of (94m)Tc production, to the best of our knowledge, previous recycling studies have been limited to the use of oxide targets. To facilitate reuse of high-power enriched (100)Mo targets, this work presents and evaluates a strategy for recycling of enriched metallic molybdenum. For the irradiated (100)Mo targets in this study, an overall metal to metal recovery of 87% is reported. Evaluation of "new" and "recycled" (100)Mo revealed no changes in the molybdenum isotopic composition (as measured via ICP-MS). For similar irradiation conditions of "new" and "recycled" (100)Mo, (i.e. target thicknesses, irradiation time, and energy), comparable levels of (94g)Tc, (95g)Tc, and (96g)Tc contaminants were observed. Comparable QC specifications (i.e. aluminum ion concentration, pH, and radiochemical purity) were also reported. We finally note that [(99m)Tc]-MDP images obtained by comparing MDP labelled with generator-based (99m)Tc vs. (99m)Tc obtained following the irradiation of recycled (100)Mo demonstrated comparable biodistribution. With the goal of producing large quantities of (99m)Tc, the proposed methodology demonstrates that efficient recycling of enriched metallic (100)Mo targets is feasible and effective.
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No pos
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No neg
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Retriever2299
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Glomerular mTORC1 activation was associated with podocytes to endothelial cells communication in lupus nephritis.
OBJECTIVE
This study was initiated to evaluate the mammalian target of the rapamycin (mTOR) signalling pathway involved in renal endothelial-podocyte crosstalk in patients with lupus nephritis (LN).
METHODS
We compared the kidney protein expression patterns of 10 patients with LN with severe endothelial-podocyte injury and 3 patients with non-severe endothelial-podocyte injury on formalin-fixed paraffin-embedded kidney tissues using label-free liquid chromatography-mass spectrometry for quantitative proteomics analysis. Podocyte injury was graded by foot process width (FPW). The severe group was referred to patients with both glomerular endocapillary hypercellularity and FPW >1240 nm. The non-severe group included patients with normal endothelial capillaries and FPW in the range of 619~1240 nm. Gene Ontology (GO) enrichment analyses were performed based on the protein intensity levels of differentially expressed proteins in each patient. An enriched mTOR pathway was selected, and the activation of mTOR complexes in renal biopsied specimens was further verified in 176 patients with LN.
RESULTS
Compared with those of the non-severe group, 230 proteins were upregulated and 54 proteins were downregulated in the severe group. Furthermore, GO enrichment analysis showed enrichment in the 'positive regulation of mTOR signalling' pathway. The glomerular activation of mTOR complex 1 (mTORC1) was significantly increased in the severe group compared with the non-severe group (p=0.034), and mTORC1 was located in podocytes and glomerular endothelial cells. Glomerular activation of mTORC1 was positively correlated with endocapillary hypercellularity (r=0.289, p<0.001) and significantly increased in patients with both endocapillary hypercellularity and FPW >1240 nm (p<0.001).
CONCLUSIONS
Glomerular mTORC1 was highly activated in patients with both glomerular endocapillary hypercellularity and podocyte injury, which might be involved in podocytes to endothelial cells communication in lupus nephritis.
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No pos
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No neg
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