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Bakgrund: Det är sedan tidigare känt att muskuloskeletala besvär inom militären är vanligt förekommande. Forskning har visat att närmare 80 % av amfibiesoldaterna inom den svenska försvarsmakten upplever någon form av muskuloskeletal smärta inom en sexmånadersperiod. Inom den svenska försvarsmaktens grundkurs amfibie (GK Amf), där grundutbildade soldater får sin amfibiespecifika träning, saknades dock kartläggning gällande förekomsten av knäsmärta. Kunskapen om detta är viktig för prevention, framtida studier och även ur ett samhällsekonomiskt perspektiv. Syfte: Syftet var att kartlägga förekomsten av självskattad knäsmärta inom den svenska försvarsmaktens fyra månader långa grundkurs amfibie. Metod: Studien byggde på en kvantitativ prospektiv observationsstudie av kohortdesign. 53 rekryter på Amfibieregementet i Berga inkluderades i studien under den 16 veckors långa GK Amf. Självskattningsformulär användes dels vid baslinjen samt vid veckovis uppföljning för att undersöka förekomst av knäsmärta. Resultat: Den totala prevalensen av upplevd knäsmärta under GK Amf var 81 % och medianen var 28%. Av samtliga 53 rekryter som riskerade smärta upplevde 42 av dem minst en episod av smärta, vilket innebar att den totala incidensen av knäsmärta under GK Amf var 79 %. Konklusion: Studien visade att förekomsten av upplevd knäsmärta var mycket hög under GK Amf. Eftersom det framkommer i studien att förekomsten av självskattad knäsmärta är hög är det relevant att i framtiden studera prevention och riskfaktorer för knäsmärta inom populationen.
Bakgrund: Dagens forskning fokuseras främst på de mätbara effekterna av fysioterapeutiska interventioner vid Parkinsons sjukdom och i mindre utsträckning på personernas upplevelser av behandling. Forskning som beskriver personers upplevelser av Lee Silverman Voice Treatment BIG (LSVT BIG) saknas.
Syfte: Att undersöka och beskriva hur personer med diagnostiserad Parkinsons sjukdom upplever instruktörsledd individuell behandling utifrån behandlingskonceptet LSVT BIG.
Metod: Kvalitativ ansats innefattande tre fokusgrupper om sammanlagt 19 personer med Parkinsons sjukdom som startat behandlingskonceptet LSVT BIG. Intervjufrågorna fokuserades på personernas upplevelser av behandlingsinterventionen. Intervjuerna transkriberades innan de analyserades genom kvalitativ innehållsanalys.
Resultat: I analysen framkom två överordnade teman;; Förutsättningar för behandlingseffekter som innefattar kategorierna En stor satsning, Betydelsen av instruktörens roll, Eget ansvar och Stöd från omgivningen. Det andra temat var Behandlingseffekter av LSVT BIG vilket innefattar kategorierna Fysiska, Psykiska och Sociala effekter samt Beteendeförändring.
Slutsats: För goda resultat av LSVT BIG krävs en stor satsning av individen, av dennes anhöriga och av vården. Den stora satsningen kräver anpassningar av behandlingsinterventionen utifrån förutsättningar hos förutnämnda parter. Instruktörens roll, stöd från närstående, självdisciplin och en känsla av att kunna påverka sin situation definierades i resultaten som motiverande faktorer som ger förutsättningar för goda behandlingseffekter. Behandlingseffekterna upplevdes som mångfacetterade och återspeglade alla delar av den biopsykosociala modellen. Tydligast framkom förbättringar av forskningspersonernas fysiska funktioner vilka upplevdes överförbara till aktiviteter i det dagliga livet.
We studied the relationship between taking part in a long-distance ski race and incidence of cardiovascular diseases (CVDs) to address the hypothesis that lifestyle lowers the incidence.
Methods and results
A cohort of 399 630 subjects in Sweden, half were skiers in the world's largest ski race, and half were non-skiers. Non-skiers were frequency matched for sex, age, and year of race. Individuals with severe diseases were excluded. The endpoints were death, myocardial infarction, or stroke. The subjects were followed up for a maximum of 21.8 years and median of 9.8 years. We identified 9399 death, myocardial infarction, or stroke events among non-skiers and 4784 among the Vasaloppet skiers. The adjusted hazard ratios (HRs) comparing skiers and non-skiers were 0.52 [95% confidence interval (CI) 0.49–0.54] for all-cause mortality, 0.56 (95% CI 0.52–0.60) for myocardial infarction and 0.63 (95% CI 0.58–0.67) for stroke and for all three outcomes 0.56 (95% CI 0.54–0.58). The results were consistent across subgroups: age, sex, family status, education, and race year. For skiers, a doubling of race time was associated with a higher age-adjusted risk of 19%, and male skiers had a doubled risk than female skiers, with a HR 2.06 (95% CI 1.89–2.41). The outcome analyses revealed no differences in risk of atrial fibrillation between skiers and non-skiers.
This large cohort study provides additional support for the hypothesis that individuals with high level of physical activity representing a healthy lifestyle, as evident by their participation in a long-distance ski race, have a lower risk of CVD or death.
Aims: To study whether a high level of physical activity prior to myocardial infarction (MI) also protects against recurrent MI (re-MI) or death.
Methods and Results: A longitudinal study of a primary cohort consisting of 204,038 skiers with a proved substantially high level of physical activity in the world's largest long-distance ski race, Vasaloppet, and 499,543 non-skiers selected from the Swedish population. Individuals with severe diseases at baseline were excluded. In the nationwide clinical register, Swedeheart, we identified 7092 individuals with a first MI incident between 1989 and 2010. Of these, 1039 (0.5%) were skiers and 6053 (1.2%) were non-skiers. One hundred and sixty-three (15.7%) skiers and 1352 (22.3%) non-skiers suffered a re-MI or died during follow-up (median 4.44 years), corresponding to an incidence rate of 38.9 (95% confidence interval (CI) 33.2-45.4)/1000 person-years and 55.6 (95% CI 52.7-58.7)/1000 person-years, respectively. Severity of MI in both groups was the same. For skiers compared to non-skiers the unadjusted hazard ratio (HR) for re-MI was 0.66 (95% CI 0.52-0.82). For death or re-MI, HR was 0.70 (95% CI 0.59-0.82) with consistent results in subgroups based on race year, age, gender, education level, marital status. After adjustment for also smoking, diabetes, hypertension and cardiovascular medication, HR was 0.80 (95% CI 0.67-0.97).
Conclusions: This large cohort study supports the hypothesis that patients with MI and with prior physical activity and healthy lifestyle, as evidenced by their participation in a long-distance ski race, have a lower risk of subsequent re-MI or death.
Aims/hypothesis: Dietary fatty acids may affect insulin sensitivity. Adipose tissue fatty acid composition partly reflects long-term dietary intake, but data from large studies regarding relationships with insulin sensitivity are lacking. We aimed to determine the association between adipose tissue fatty acids and insulin sensitivity in elderly Swedish men. Methods In a cross-sectional analysis of the community-based Uppsala Longitudinal Study of Adult Men (n?=?795, mean age 71 years), adipose tissue biopsies were obtained and fatty acid composition was determined by gas–liquid chromatography. Insulin sensitivity was measured directly by a euglycaemic clamp. Results Palmitic acid (16:0), the major saturated fatty acid (SFA) in the diet and in adipose tissue, was negatively correlated with insulin sensitivity (r?=?-0.14), as were 16:1 n-7 (r?=?-0.15), 20:3 n-6 (r?=?-0.31), 20:4 n-6 (r?=?-0.38), 22:4 n-6 (r?=?-0.37) and 22:5 n-3 (r?=?-0.24; p?<?0.001 for all). Some minor SFAs were positively correlated; 12:0 (r?=?0.46), 14:0 (r?=?0.32), 17:0 (r?=?0.21) and 18:0 (r?=?0.41; p?<?0.001 for all), as were essential polyunsaturated fatty acids (PUFAs) 18:2 n-6 (r?=?0.10, p?<?0.01) and 18:3 n-3 (r?=? 0.16, p?<?0.001). Docosahexaenoic acid (22:6 n-3) was negatively correlated (r?=?-0.11, p?<?0.01), whereas eicosapentaenoic acid (20:5 n-3) was not (r?=?-0.02, NS). Most associations diminished or disappeared in lean individuals, indicating an effect of obesity. Conclusions/interpretation Adipose tissue enriched with palmitic acid and depleted of essential PUFAs is associated with insulin resistance. The positive association between minor SFAs and insulin sensitivity merits further investigation.
BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study.
METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001).
CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA.
CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.
Importance: The major polyunsaturated fatty acids in adipose tissue objectively reflect long-term dietary intake, and may provide more reliable information than would self-reported intake. Whether adipose tissue fatty acids predict cardiovascular and all-cause mortality needs investigation.
Objective: To investigate associations between adipose tissue fatty acids and cardiovascular and overall mortality in a cohort of elderly men.
Design, Setting, and Participants: We hypothesized that polyunsaturated fatty acids reflecting dietary intake, are inversely associated with cardiovascular and all-cause mortality. In the Swedish cohort study Uppsala Longitudinal Cohort of Adult Men, buttock fatty acid composition was analyzed by gas-liquid chromatography in 1992 to 1993 and 2008. The study participants were followed during 11 311 person-years, between 1991 and 2011 (median follow-up, 14.8 years). In this community-based study that took place from 1970 to 1973, all men born in 1920 to 1924 in Uppsala, Sweden, were invited and 2322 (82%) were included (at age 50 years). At the reinvestigation at age 71 years, 1221 (73%) of the 1681 invited men participated. Adipose tissue biopsy specimens were taken in a subsample of 853 men. There was no loss to follow-up.
Exposures: Adipose tissue proportions of 4 polyunsaturated fatty acids that were considered to mainly reflect dietary intake (linoleic acid, 18:2n-6; α-linolenic acid, 18:3n-3; eicosapentaenoic acid, 20:5n-3; and docosahexaenoic acid, 22:6n-3) comprised primary analyses, and all other available fatty acids were secondary analyses.
Main Outcomes and Measures: Hazard ratios (HRs) for cardiovascular and all-cause mortality using Cox proportional hazards regression analyses, performed in 2015.
Results: Among the 853 Swedish men, there were 605 deaths, of which 251 were cardiovascular deaths. After adjusting for risk factors, none of the 4 primary fatty acids were associated with cardiovascular mortality (HR, 0.92-1.05 for each standard deviation increase; P ≥ .27). Linoleic acid was inversely associated with all-cause mortality (HR, 0.90; 95% CI, 0.82-0.98; P = .02) and directly associated with intake (P < .001). In secondary analyses, palmitoleic acid, 16:1n-7 (HR, 1.11; 95% CI, 1.02-1.21; P = .02) was associated with higher all-cause mortality, whereas heptadecanoic acid, 17:0, tended to be associated with lower all-cause mortality (HR, 0.89; 95% CI, 0.79-1.00; P = .05). Arachidonic:linoleic acid ratio was associated with both cardiovascular (HR, 1.15; 95% CI, 1.05-1.31; P = .04) and all-cause (HR, 1.13; 95% CI, 1.04-1.23; P = .005) mortality.
Conclusions and Relevance: Adipose tissue linoleic acid was inversely associated with all-cause mortality in elderly men, although not significantly with cardiovascular mortality.
Objective: Our aim was to examine relations of serum retinol-binding protein 4 (RBP4) to cardiovascular risk factors, and prevalent metabolic syndrome (MetS) and cardiovascular disease (CVD) in a large community-based sample of elderly.
Methods: We evaluated cross-sectional relations of serum RBP4 to cardiovascular risk factors including anthropometrical measures, blood pressure, lipid measures, fasting glucose and insulin, body fat distribution including truncal fat by dual-energy x-ray absorptiometry (DXA), homeostasis model assessment insulin resistance (HOMA-IR) and prevalent MetS in one thousand eight 70-year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in five hundred seven 82-year old men from Uppsala Longitudinal Study of Adult Men (ULSAM). In ULSAM, we also examined associations with prevalent CVD.
Results: RBP4 concentrations were positively correlated with serum triglycerides (r = 0.30; P < 0.0001 in both samples), whereas correlations with body mass index (BMI), waist circumference, sagittal abdominal diameter, total and truncal fat mass, total cholesterol, fasting glucose and HOMA-IR were weak. In multivariable-adjusted models, RBP-4 was associated with MetS (odds ratio (OR), 1.16 and 1.33; 95% confidence interval (CI), 0.99–1.37 and 1.05–1.67 per 1-standard deviation (SD) increase in PIVUS and ULSAM, respectively), and prior cerebrovascular disease (OR, 1.37; 95% CI, 1.00-1.88 per 1-SD increase in ULSAM), but not with prior myocardial infarction.
Conclusion: In elderly, RBP4 concentrations were associated with MetS and its components in both sexes, and prior cerebrovascular disease in men. These findings are consistent with the hypothesis that circulating RBP4 could be a marker of metabolic complications and possibly also atherosclerosis and overt CVD.
Context: Skeletal muscle morphology and function are strongly associated with insulin sensitivity.
Objective: The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity.
Design, Settings, and Participants: This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study.
Main Outcome Measures: Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies.
Results: In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (β, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (β, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (β, −0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (β difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (β difference, −0.053; 95% confidence interval −0.107, −0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models.
Conclusions: Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.
Circulating adiponectin concentrations are associated with skeletal muscle morphology and could be involved in the relations between muscle morphology and insulin sensitivity.
BACKGROUND: The long-term trajectories of lipid and glucose levels in subjects who experience a major cardiovascular (CV) event at a young age has not been well studied. Our objective was to investigate lipid, lipoprotein, apolipoprotein (apo), and glucose levels in individuals experiencing a CV event before 50 years of age.
METHODS AND FINDINGS: A first CV event [non-fatal myocardial infarction (MI), coronary revascularisation, or CV related death] before age 50 was recorded in 2,939 (cumulative incidence 1.2% in males and 0.3% in females) of 361,353 individuals included in the prospective Swedish AMORIS (Apolipoprotein-related MOrtality RISk) study with health examinations 1985-1996 and follow-up through 2011. In a nested case-control analysis, cases with a CV event were matched to randomly selected controls. Population risk factor trajectories were calculated up to 20 years prior to an event. Total cholesterol (TC), triglyceride (TG), and glucose levels were higher in cases than in controls as early as 20 years prior to the event with differences increasing over time. Low density lipoprotein, apoB, and the apoB/apoA-1 ratio were higher and increased over time, while HDL and apoA-1 were lower in cases compared to controls. The odds ratio was 2.5 (95% confidence interval 1.6-3.7) for TC ≥5 mmol/L and TG ≥1.7 mmol/L in cases versus controls. The adjusted population-attributable fractions including lipids, glucose, diabetes, smoking, hypertension, and obesity indicated that about 50% of CV events before age 50 may be associated with elevated lipid and glucose levels.
CONCLUSIONS: Elevated TC, TG, LDL, apoB, and glucose levels and high apoB/apo A-1 ratio documented two decades before a CV event in subjects younger than 50 years may account for about half of CV events before age 50, which calls for early recognition and possibly treatment of modifiable CV risk factors in young individuals.
BACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.
STUDY DESIGN: Meta-analysis of cohort studies.
SETTING & POPULATION: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.
SELECTION CRITERIA FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium.
PREDICTORS: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.
OUTCOME: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.
RESULTS: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.
LIMITATIONS: AKI identified by diagnostic code.
CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.
Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data.
Methods We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting.
Findings Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 39% (95% uncertainty interval [UI] 3.1-4. 6) from 1990 to 2017; however, the all-age YLD rate increased by 7.2% (6.0-8.4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7.9% (6 6-9. 2) for males and 6.5% (5.4-7.7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-hatin and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]).
Interpretation Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury.
As chronic kidney disease (CKD) progresses with abnormalities in glucose and insulin metabolism, commonly used insulin sensitivity indices (ISIs) may not be applicable in individuals with CKD. Here we sought to validate surrogate ISIs against the glucose disposal rate by the gold-standard hyperinsulinemic euglycemic glucose clamp (HEGC) technique in 1074 elderly men of similar age (70 years) of whom 495 had and 579 did not have CKD (estimated glomerular filtration rate (eGFR) under 60 ml/min per 1.73 m(2) (median eGFR of 46 ml/min per 1.73 m(2))). All ISIs provided satisfactory (weighted κ over 0.6) estimates of the glucose disposal rate in patients with CKD. ISIs derived from oral glucose tolerance tests (OGTTs) agreed better with HEGC than those from fasting samples (higher predictive accuracy). Regardless of CKD strata, all ISIs allowed satisfactory clinical discrimination between the presence and absence of insulin resistance (glucose disposal rate under 4 mg/kg/min). We also assessed the ability of both HEGC and ISIs to predict all-cause and cardiovascular mortality during a 10-year follow-up. Neither HEGC nor ISIs independently predicted mortality. Adjustment for renal function did not materially change these associations. Thus, ISIs can be applied in individuals with moderately impaired renal function for diagnostic purposes. For research matters, OGTT-derived ISIs may be preferred. Our data do not support the hypothesis of kidney function mediating insulin sensitivity (IS)-associated outcomes nor a role for IS as a predictor of mortality.Kidney International advance online publication, 29 January 2014; doi:10.1038/ki.2014.1.
Context: Kidney dysfunction induces insulin resistance, but it is unknown if β cell function is affected.
Objective: To investigate insulin release (β cell function) and glucose tolerance following a standardized oral glucose tolerance test (OGTT) across kidney function strata.
Setting and Design: Community-based cohort study from the Uppsala Longitudinal Study of Adult Men (ULSAM).
Participants and Main Outcome Measure: Included were 1015 non-diabetic Swedish men aged 70-71 years. All participants underwent OGTT and euglycaemic hyperinsulinaemic clamp (HEGC) tests, allowing determination of insulin sensitivity, β cell function and glucose tolerance. Kidney function was estimated by cystatin C-algorithms. Mixed models were used to identify determinants of insulin secretion after the hyperglycemic load.
Results: As many as 466 (46%) of participants presented moderate-advanced kidney disease. Insulin sensitivity (by HEGC) decreased across decreasing kidney function quartiles. After the OGTT challenge, however, β cell function indices (area under the curve for insulin release, the estimated first phase insulin release and the insulinogenic index) were incrementally higher. Neither the oral disposition index nor ths 2-hour post-load glucose tolerance differed across kidney function strata. Mixed models showed that dynamic insulin release during the OGTT was inversely associated to kidney function despite correction for each individual's insulin sensitivity or its risk factors.
Conclusions: In older men, β cell function after a hyperglycemic load appropriately compensated the loss in insulin sensitivity that accompanies kidney dysfunction. As a result, the net balance between insulin sensitivity and β cell function was preserved.
Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.
The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.
This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.
In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.
Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations.
BACKGROUND: Increased circulating cathepsin S levels have been linked to increased risk of cardiometabolic diseases and cancer. However, whether cathepsin S is a modifiable risk factor is unclear. We aimed to investigate the effects of a prudent diet on plasma cathepsin S levels in healthy individuals.
FINDINGS: Explorative analyses of a randomized study were performed in 88 normal to slightly overweight and hyperlipidemic men and women (aged 25 to 65) that were randomly assigned to ad libitum prudent diet, i.e. healthy Nordic diet (ND) or a control group (habitual Western diet) for 6 weeks. Whereas all foods in the ND were provided, the control group was advised to consume their habitual diet throughout the study. The ND was in line with dietary recommendations, e.g. low in saturated fats, sugars and salt, but high in plant-based foods rich in fibre and unsaturated fats.The ND significantly decreased cathepsin S levels (from 20.1 (+/-4.0 SD) to 19.7 μg/L (+/-4.3 SD)) compared with control group (from 18.2 (+/-2.9 SD) to 19.1 μg/L (+/-3.8 SD)). This difference remained after adjusting for sex and change in insulin sensitivity (P = 0.03), and near significant after adjusting for baseline cathepsin S levels (P = 0.06), but not for change in weight or LDL-C. Changes in cathepsin S levels were directly correlated with change in LDL-C.
CONCLUSIONS: Compared with a habitual control diet, a provided ad libitum healthy Nordic diet decreased cathepsin S levels in healthy individuals, possibly mediated by weight loss or lowered LDL-C. These differences between groups in cathepsin S were however not robust and therefore need further investigation.
Context: Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking. Objective To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women.
Design, Setting, and Participants: Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010). Serum samples were used to measure cathepsin S.
Main Outcome Measure Total mortality.
Results: During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P = .009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P = .04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P = .01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10]; P = .01).
Conclusions Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.
Objective: Cathepsin S has been suggested provide a mechanistic link between obesity and atherosclerosis, possibly mediated via adipose tissue-derived inflammation. Previous data have shown an association between circulating cathepsin S and inflammatory markers in the obese, but to date, community-based reports are lacking. Accordingly, we aimed to investigate the association between serum levels of cathepsin S and markers of cytokine-mediated inflammation in a community-based sample, with prespecified subgroup analyses in nonobese participants.
Methods: Serum cathepsin S, C-reactive protein (CRP), and IL-6 were measured in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men; mean age 71 years, n = 991). CRP and IL-6 were also measured at a reexamination after 7 yr.
Results: After adjustment for age, body mass index, fasting plasma glucose, diabetes treatment, systolic blood pressure, diastolic blood pressure, hypertension treatment, serum cholesterol, serum high-density lipoprotein cholesterol, prior cardiovascular disease, smoking, and leisure time physical activity, higher cathepsin S was associated with higher CRP (regression coefficient for 1 SD increase, 0.13; 95% confidence interval 0.07–0.19; P < 0.001) and higher serum IL-6 (regression coefficient for 1 SD increase, 0.08; 95% confidence interval 0.01–0.14; P = 0.02). These associations remained similar in normal-weight participants (body mass index <25 kg/m2, n = 375). In longitudinal analyses, higher cathepsin S at baseline was associated with higher serum CRP and IL-6 after 7 yr.
Conclusions: These results provide additional evidence for the interplay between cathepsin S and inflammatory activity and suggest that this association is present also in normal-weight individuals in the community.
Cathepsin S is independently associated with cytokine mediated inflammation in elderly men Conclusion: Higher serum levels of Cathepsin S were independently associated with higher CRP and IL-6 in a community– based sample of elderly men. Our data provides support for the notion that Cathepsin S is involved in inflammatory processes, possibly leading to atherosclerosis and cardiovascular disease. Background: Cathepsin S is a lysosomal protease that has been suggested to play a key role in the development of atherosclerosis and cardiovascular disease by degradation of vascular extracellular matrix. Previous studies have suggested that cathepsin S provides a molecular link between obesity and atherosclerosis, possibly via increased inflammatory activity. Yet, the association between circulating cathepsin S and inflammation markers has not previously been reported in the community. Aim: To investigate the association between plasma levels of cathepsin- S, C-reactive protein (CRP) and Interleukin 6 (IL-6), in the community. Methods: Serum levels of cathepsin S, CRP, IL-6 were measured in frozen samples from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (n=999, mean age 71 years). Results: Cross-sectional association between Cathepsin S, CRP and IL-6 at age 70 showed that one standard deviation (SD) higher serum Cathepsin S was significantly associated with 0.14 SD higher serum CRP and 0.07-0.08 SD higher serum IL-6 when adjusting for age, life style factors (body mass index, physic activity and smoking), cardiovascular risk factors (hypertension, dyslipidemia, previous cardiovascular disease and diabetes and smoking), and the combination of all covariates
OBJECTIVE. To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.
RESEARCH DESIGN AND METHODS. Serum cathepsin S, insulin sensitivity (euglycaemic-hyperinsulinaemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.
RESULTS. After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).
CONCLUSIONS. Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.
A technique for multiplex detection of pathogens based on padlock probes and Luminex technology has been developed. Here detection data from a panel of pathogenic fungi is presented.
Most nucleic acid based techniques in use for clinical pathogen detection (diagnosis) can reveal one to a few pathogens in each test. Techniques revealing several pathogens at a time are often problematic due to inherent difficulties with multiplex PCR. The padlock probe (PLP) based detection method, presented here, avoids such problems and has potential for developing highly multiplexed assays.
A PLP is an oligonucleotide designed to hybridize to a target sequence so that the 5' and 3' end of the probe meet with only a nick separating them. A ligase can close the nick, forming a closed DNA circle of the probe. In the case presented here the internal parts of the probe (the parts not participating in target hybridization) have a general PCR primer target region and a DNA address region (tag region). General PCR primers, that are labelled, can amplify circularized probes and the products can be detected in a Luminex™ machine via the address tags.
Oligonucleotide microarrays are used to analyze target sequences on the basis of differences in hybridization stability between matched and mismatched probe-target duplexes. DNA microarray manufacture via photolithographic synthesis generates a minority of full-length oligonucleotide probes along with a series of 5'-truncated contaminants. In a model experiment, we now investigate the effect of truncated oligonucleotides on the ability to distinguish target sequence variants that differ in a single nucleotide position. A series of oligonucleotides, mixed in proportions simulating stepwise synthetic yields of between 82 and 100%, were bound to a solid support and allowed to hybridize to a target molecule. The extent of hybridization was monitored over a range of temperatures via the fluorescence of a double-strand-specific dye. The discriminatory power of pure oligonucleotide probes was found to be significantly greater than that of a population of truncated probes, but only over a limited temperature interval. We conclude that at optimal temperatures greater oligonucleotide quality can improve the performance of oligonucleotide hybridization microarrays.
Catalogs of intra-gene polymorphisms are needed to facilitate wide-ranging candidate gene-based association studies in common complex diseases. With this in mind, we have scanned multiple alignments of expressed sequence tags and of genomic DNA sequences (PCR products from four to eight unrelated individuals) to find polymorphisms in 195 genes putatively involved in neurodegenerative illness (including components of oxidative stress, excitotoxicity, inflammation, apoptosis and aging). This led to the discovery of 167 polymorphisms in 88 genes. These comprised 163 single nucleotide polymorphisms, one insertion/deletion, and three other variations involving more than one base pair. The polymorphisms were distributed in the exons (87), introns (70), and gene flanking regions (10). Of the exonic polymorphisms, 17 would give rise to non-synonymous amino acid substitutions. These findings now provide a valuable resource for association studies in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.
Fluorescence resonance energy transfer (FRET) is a powerful tool for detecting spatial relationships between macromolecules, one use of which is the tracking of DNA hybridization status. The process involves measuring changes in fluorescence as FRET donor and acceptor moieties are brought closer together or moved farther apart as a result of DNA hybridization/denaturation. In the present study, we introduce a new version of FRET, which we term induced FRET (iFRET), that is ideally suited for melting curve analysis. The innovation entails using a double-strand, DNA-specific intercalating dye (e.g., SYBR Green I) as the FRET donor, with a conventional FRET acceptor affixed to one of the DNA molecules. The SNP genotyping technique dynamic allele specific hybridization (DASH) was used as a platform to compare iFRET to two alternative fluorescence strategies, namely, the use of the intercalating dye alone and the use of a standard FRET pair (fluorescein as donor, 6-rhodamine as acceptor). The iFRET configuration combines the advantages of intercalating dyes, such as high signal strengths and low cost, with maintaining the specificity and multiplex potential afforded by traditional FRET detection systems. Consequently, iFRET represents a fresh and attractive schema for monitoring interactions between DNA molecules.
We recently introduced a generic single nucleotide polymorphism (SNP) genotyping method, termed DASH (dynamic allele-specific hybridization), which entails dynamic tracking of probe (oligonucleotide) to target (PCR product) hybridization as reaction temperature is steadily increased. The reliability of DASH and optimal design rules have not been previously reported. We have now evaluated crudely designed DASH assays (sequences unmodified from genomic DNA) for 89 randomly selected and confirmed SNPs. Accurate genotype assignment was achieved for 89% of these worst-case-scenario assays. Failures were determined to be caused by secondary structures in the target molecule, which could be reliably predicted from thermodynamic theory. Improved design rules were thereby established, and these were tested by redesigning six of the failed DASH assays. This involved reengineering PCR primers to eliminate amplified target sequence secondary structures. This sophisticated design strategy led to complete functional recovery of all six assays, implying that SNPs in most if not all sequence contexts can be effectively scored by DASH. Subsequent empirical support for this inference has been evidenced by ~30 failure-free DASH assay designs implemented across a range of ongoing genotyping programs. Structured follow-on studies employed standardized assay conditions, and revealed that assay reproducibility (733 duplicated genotypes, six different assays) was as high as 100%, with an assay accuracy (1200 genotypes, three different assays) that exceeded 99.9%. No post-PCR assay failures were encountered. These findings, along with intrinsic low cost and high flexibility, validate DASH as an effective procedure for SNP genotyping.
Dynamic allele specific hybridization (DASH) [1] is a method for
genotyping single nucleotide polymorphisms (SNPs), insertion/deletions
(indels), and other subtle sequence variations. Allele discrimination
is based upon the detection of stability differences in duplex
DNAs (oligonucleotide probes hybridized to PCR product targets)
involving fully matched or allelic-mismatched structures. The procedure
involves PCR amplification of a short sequence spanning a variant
position. One PCR primer is biotinylated allowing subsequent
facile affinity (streptavidin) capture of one strand of the PCR product
onto a solid support. An unlabelled oligonucleotide probe, complementary
to one of the alleles, is then annealed to this target DNA at
low temperature in the presence of a double-strand specific intercalating
dye. Samples are then steadily heated through a temperature
range while continually monitoring fluorescence, i.e., the amount of
duplexed probe-target material. A melting temperature profile is thus
derived, indicating the presence of perfectly matched or subtly mismatch
probe-target duplexes, or a heterozygous mixture of the two.
An extensive testing and validation study was performed in order
to maximize the utility of DASH. This study involved design and
application of DASH assays for 89 randomly selected SNPs. Nonoptimized
assay designs (worst-case scenario) resulted in 79 functional
assays from which genotypes could be clearly determined.
Statistical analysis of many variables in these assays revealed that the
presence or absence of secondary structures in the target sequence
was a critical factor for DASH performance. By identifying key bases
involved in secondary structure formation and then by altering these
in the PCR primers, the formation of secondary structure could be
minimized. Six of the failed DASH assays were redesigned following
this strategy, and full recovery of all six assays was achieved (bestcase
scenario). Subsequent replication and method comparison studies
demonstrated that DASH achieves a genotyping accuracy better than
99.9%, and a reproducibility of 100%. No post-PCR assay failures
have yet been encountered. These findings, along with intrinsic low
cost (less than 25c/genotype) and high flexibility, validate DASH as
an effective procedure for SNP genotyping.
Genetic linkage and association analyses are two distinct approaches to understanding the genetic etiology of complex disease. Association analysis has become particularly popular in recent times, but the true utility of the strategy remains uncertain. To try to gain better insight into the relevant issues, we have used genetic association analysis to explore the etiology of Alzheimer's disease. Our empirical findings supplement the theoretical debate, illustrating the general doubtfulness of previous positive findings and the limited ability of typical association studies based on candidate genes to discern true medium-sized signals from false positives. Improvements in genotyping technologies and increasing the number of SNPs tested, without sophisticated allowance for all other issues, could simply lead to an unmanageable overload of false-positive signals, themselves obscuring true disease associations
BACKGROUND: Modelling and analysing repeated measures data, such as women's experiences of pain during labour, is a complex topic. Traditional end-point analyses such as t-tests, ANOVA, or repeated measures [rANOVA] have known disadvantages. Modern and more sophisticated statistical methods such as mixed effect models provide flexibility and are more likely to draw correct conclusions from data. The aim of this study is to study how labour pain is analysed in repeated measures design studies, and to increase awareness of when and why modern statistical methods are suitable with the aim of encouraging their use in preference of traditional methods.
METHODS: Six databases were searched with the English language as a restriction. Study eligibility criteria included: Original studies published between 1999 and 2016, studying pregnant women in labour with the aim to compare at least two methods for labour pain management, with at least two measurements of labour pain separated by time, and where labour pain was analysed. After deduplication, all records (n = 2800) were screened by one of the authors who excluded ineligible publication types, leaving 737 records remaining for full-text screening. A sample of 309 studies was then randomly selected and screened by both authors.
RESULTS: Among the 133 (of 309) studies that fulfilled the study eligibility criteria, 7% used mixed effect models, 20% rANOVA, and 73% used end-point analysis to draw conclusions regarding treatment effects for labour pain between groups. The most commonly used end-point analyses to compare groups regarding labour pain were t-tests (57, 43%) and ANOVA (41, 31%). We present a checklist for clinicians to clarify when mixed effect models should be considered as the preferred choice for analysis, in particular when labour pain is measured.
CONCLUSIONS: Studies that aim to compare methods for labour pain management often use inappropriate statistical methods, and inaccurately report how the statistical analyses were carried out. The statistical methods used in analyses are often based on assumptions that are not fulfilled or described. We recommend that authors, reviewers, and editors pay greater attention to the analysis when designing and publishing studies evaluating methods for pain relief during labour.
Background: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100 000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.
Methods: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.
Findings: 292 982 (95% UI 261017-327792) maternal deaths occurred in 2013, compared with 376 034 (343483-407574) in 1990. The global annual rate of change in the MMR was -0.3% (-1.1 to 0.6) from 1990 to 2003, and -2.7% (-3.9 to -1.5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0.4% (-0.2-0.6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956.8 (685.1-1262.8) in South Sudan to 2.4 (1.6-3.6) in Iceland.
Interpretation: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.
Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development.
We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate.
Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9–3·0) for men and 3·5 years (3·4–3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78–0·92) and 1·2 years (1·1–1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs.
Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
Bill & Melinda Gates Foundation
In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015.
We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10–54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specific reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility.
Only ten countries achieved MDG 5, but 122 of 195 countries have already met SDG 3.1. Geographical disparities widened between 1990 and 2015 and, in 2015, 24 countries still had a maternal mortality ratio greater than 400. The proportion of all maternal deaths occurring in the bottom two SDI quintiles, where haemorrhage is the dominant cause of maternal death, increased from roughly 68% in 1990 to more than 80% in 2015. The middle SDI quintile improved the most from 1990 to 2015, but also has the most complicated causal profile. Maternal mortality in the highest SDI quintile is mostly due to other direct maternal disorders, indirect maternal disorders, and abortion, ectopic pregnancy, and/or miscarriage. Historical patterns suggest achievement of SDG 3.1 will require 91% coverage of one antenatal care visit, 78% of four antenatal care visits, 81% of in-facility delivery, and 87% of skilled birth attendance.
Several challenges to improving reproductive health lie ahead in the SDG era. Countries should establish or renew systems for collection and timely dissemination of health data; expand coverage and improve quality of family planning services, including access to contraception and safe abortion to address high adolescent fertility; invest in improving health system capacity, including coverage of routine reproductive health care and of more advanced obstetric care—including EmOC; adapt health systems and data collection systems to monitor and reverse the increase in indirect, other direct, and late maternal deaths, especially in high SDI locations; and examine their own performance with respect to their SDI level, using that information to formulate strategies to improve performance and ensure optimum reproductive health of their population.
Bill & Melinda Gates Foundation.
Importance Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health.
Objective To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion.
Evidence Review Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed (Socio-demographic Index [SDI]) for each geographic unit and year, which evaluates the historical association between SDI and health loss.
Findings Global child and adolescent mortality decreased from 14.18 million (95% uncertainty interval [UI], 14.09 million to 14.28 million) deaths in 1990 to 7.26 million (95% UI, 7.14 million to 7.39 million) deaths in 2015, but progress has been unevenly distributed. Countries with a lower SDI had a larger proportion of mortality burden (75%) in 2015 than was the case in 1990 (61%). Most deaths in 2015 occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden. The absolute burden of disability in children and adolescents increased 4.3% (95% UI, 3.1%-5.6%) from 1990 to 2015, with much of the increase owing to population growth and improved survival for children and adolescents to older ages. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth (eg, neonatal disorders, congenital birth defects, and hemoglobinopathies) and complications of a variety of infections and nutritional deficiencies. Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries.
Conclusions and Relevance Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.
Background: Nutritional supplementation may potentiate the increase in skeletal muscle protein synthesis following exercise in healthy older individuals. Whether exercise and nutrition act synergistically to produce sustained changes in physical functioning and body composition has not been well studied, particularly in mobility-limited older adults.
Methods: The VIVE2 study was a multi-center, randomized controlled trial, conducted in the United States and Sweden. This study was designed to compare the effects of a 6-month intervention with a once daily, experimental, 4fl. oz. liquid nutritional supplement providing 150kcal, whey protein (20g), vitamin D (800IU) (Nestlé Health Science, Vevey, Switzerland), to a low calorie placebo drink (30kcal, non-nutritive; identical format) when combined with group-based exercise in 150 community-dwelling, mobility-limited older adults. All participants participated in a structured exercise program (3 sessions/week for 6months), which included aerobic, strength, flexibility, and balance exercises.
Results: The primary outcome was 6-month change in 400m walk performance (m/s) between supplement and placebo groups. Secondary outcomes included 6month change in: body composition, muscle cross-sectional area, leg strength, grip strength, stair climb time, quality of life, physical performance, mood/depressive symptoms and nutritional status. These outcomes were selected based on their applicability to the health and well-being of older adults.
Conclusions: The results of this study will further define the role of nutritional supplementation on physical functioning and restoration of skeletal muscle mass in older adults. Additionally, these results will help refine the current physical activity and nutritional recommendations for mobility-limited older adults.
BACKGROUND & AIMS: Proton pump inhibitors (PPI) have been associated with acute kidney injury (AKI) and recent studies suggest that they may be associated with the risk of chronic kidney disease (CKD).
METHODS: We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n= 105305) and new users of H2 blockers (H2B; n= 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury (AKI). Complete collection of repeated PPI and H2B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated to cumulative PPI exposure.
RESULTS: Users of PPIs, compared to users of H2Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio [HR], 1.26; 95% CI, 1.05-1.51) and decrease in estimated glomerular filtration rate of 30% or more (11045 events; 1.26; 95% CI, 1.16-1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 0.76-7.58) and AKI (HR, 1.30; 95% CI, 1.00-1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H2B use.
CONCLUSIONS: Initiation of PPI therapy and cumulative PPI exposure associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.
eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m(2) (a difference of 20 ml/min per 1.73 m(2)) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m(2).


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Not like it used to be. Prime rib night advertised but they did not have the special. No more booths . Very few dinner entree choices. Too noisy.
The food was amazing, and service outstanding!
Family vacation in Rancho Mirage
Family outing for dinner of 9 including kids ages 6 and 3. I was impressed our waiter asked our 3 year old Granddaughter personally what she wanted to order for her meal. So she ordered her own meal for herself! That is a first for her. Thank you! The food was delicious, the restaurant was upbeat, fun and yet relaxing for the family after a full day out on the trails. Something every restaurant should be able to claim is we could actually have a conversation across the table. This does not happen very often. Thank you!
Thanksgiving vacation
Went as a group, food was good! Resort is higher cost than what this restaurant would be if off property.
Most enjoyable
Food, drinks and service were amazing! We started off with the Calamari trips appetizer. chimichurri and tartar sauce to dip. Unreal! Husband had the Steak Frites, cooked to perfection. I had the Sea Scallops, also grilled perfectly . Server was attentive without being intrusive. Shout out to Justin! Thank you for making our anniversary dinner so enjoyable!
Perfect weather and music from the Palm Plaza made this an enjoyable Friday evening. I had the chicken quinoa and my spouse had the French dipped sandwich. Both were excellent. We enjoyed our traditional Seghesio Zinfandel with excellent service from Sarah and the rest of the staff. A pleasant evening.
Always enjoy dinning here. The food, service & ambiance is top notch.
Perfect weather, music, food, wine and service from Brandon. We will be back. We enjoy the whole experience and the entire staff makes us feel at home.
This is a restaurant that is best for breakfast or perhaps lunch. We had a party of 9 and had to be seated inside and the interior lacks ambiance. Service was friendly but slow. The food was good but not great and unmemorable.
Breakfast the following morning outside on the patio, just a party of 3, was excellent, especially the chorizo /cheese quesadillas. If we return to the resort, we might try Morgan's instead or do as we did and eat in Palm Springs.
Everything was great. One star ticked off though. What's up with Sunday brunch ending at 11? Our reservation was for 11:15, kinda lame. Had I known, I would have gone some place else because I wanted breakfast food. Worse, there was still a breakfast buffet up, fully loaded, and we weren't allowed to use it. What a slap in the face. 😕
Still, we were good sports and ordered from the lunch menu. Food was very tasty. I would implore Twenty6 to consider extending their brunch hours by at least an hour. Weekends are all about brunch!
Friday night in season and the place to be is Twenty Six on the patio at 6 pm for the start of live music. I had chicken quinoa and my wife had grilled salmon cooked medium with Romesco sauce. We shared a bottle of Seghesio Zinfandel and Brandon provided excellent service. Perfect weather for a perfect evening.
We ate on the patio as It's October and the weather is perfect and the music from the Palm Patio added ambiance. I had grilled chicken quinoa and it was delicious but too large to finish. My wife had the salmon cooked medium and the piece of salmon was huge. We downed our food with a bottle of Seghesio Zinfandel and Brandon provided professional service.
The breakfast brunch buffet was awesome! They had an omelet station, pancakes, waffles, bacon and sausage, and an array of fruit. There are also tons of baked goods, including gluten free. The service was odd. They were very nice, but would disappear for long periods of time. They would check on you, and then after that disappear for 10-plus minutes. It was just weird, because there were tons of servers oh, and then there weren't. Overall, I would be back, and the food was good.
The cooler October weather is back, and it provided for a great evening. We dined on the patio of Twenty-six to listen to the live music coming from the Palm Patio. I had the quinoa chicken salad and my wife had the grilled salmon with romesco sauce and a bottle of Seghesio Zinfandel wine. First time she tried romesco sauce and she thought it was tasty. Brandon was a very attentive server even though it was quite busy. We'll definitely return in a few weeks.
Our server Eduardo was great! The selections that he recommended were SPOT ON! The ambiance was lovely!
Unfortunately, the salmon was much too salty.
Salad was good
It's October so we are back in season and the weather is perfect for sitting outside on the patio. I had the grilled chicken quinoa and it is my new favorite. My wife had the beef sandwich and she looked forward to it all week and it did not disappoint. This coupled with a bottle of zinfandel , the spot on perfect service by Brandon and Eduardo and the music from the Palm Plaza make it a reason to come back next weekend.
Great food. But by the time I got back to my room I had a really bad explosive tummy. Must be a coincidence. A shame as the food was amazing. Had breakfast the next day and in the butter dish it was clearly dirty as it had left over bits of green stuck to the inside. I'm guess sanitation is not a strong ambition here
La Quinta Resort is a wonderful venue, but they just can't get it right. From waiting 15 minutes for the forgotten dressing for our dinner salads to waiting over 30 minutes to get a correct dinner bill, TWENTY6 ruined a beautiful evening.
As a member of an associated facility, our club offers us a 20% discount on food as an enticement to use the facilities at the resort. However, when we wanted to split the bill, the waiter and manager refused to honor the discount for my guests.
Mediocre food and service, unskilled and argumentative management, beautiful setting and great entertainment.
It was an experience
Venue is fine, but the food and drinks are overpriced .
Great place. Off season so not as crowded. Yummy burger. Get the garlic tater tots! Great service. Very attentive.
It's a casual dining experience with upscale prices. There was no host at the door, we stood there without any acknowledgement. The food was not prepared as advertised in the menu. It was very disappointing. I will never go back.
The food was delicious! We enjoyed dinner here during our stay. Will definitely return.
Great setup. Easy access to food for the breakfast Buffett. Also provides great atmosphere for dinner service. Reasonably priced compared to surrounding restaurants.
I usually do not like sauces, but this chef's use of seasonings makes them truly exceptional. I have found that on multiple visits with different dishes. As a hotel and spa offering, Twenty6 is truly superb. The food is creative while always maintaining a menu consistent with La Quinta's long history as a traditional Hollywood retreat. The dishes will prove familiar to Travelers from any part of the country and much of the world, while still giving each dish a creative twist.
The food and service were good. My waiter was very attentive.
I had eaten at this restaurant a few days earlier and was seated outside. The flies were so annoying. I was inside for this particular meal and the flies were just as annoying. Something should be done about them!
Many pesky flies in the dining room.
Tater tots were greasy.
Soup served after entree.
Expected much better from a Waldorf Astoria property and at this price point.
For the prices that are charged (way too high), we were expecting something more than a 'cafe' setting. There were guests wearing pool attire, and parents bringing in kids making way too much noise. Food was just okay, way overpriced for such a casual environment and mediocre food. What a disappointment, there are far better places to spend that kind of money.
It was 102 on the patio and it still felt comfortable. I had the beet salad with salmon and my wife had beet salad with shrimp and they were huge. Both were lite and perfect for a summer night. Eduardo tempted us with their delicious July 4th dessert a chocolate ice cream mud pie. Music 🎶 from the Palm Plaza created a great evening.
Staying at LaQuinta so we decided to dine here for a late breakfast early lunch
I had their lunch special which was a tuna melt, salad and navy bean soup (my Fathers favorite)
It was awesome
I think that it was a tuna steak that was cooked then shredded
Cheese and sour dough bread finished it off
Wife had the buffet, bacon looked spectacular
Not cheap but at least solid meals
This is another great one for dinner if you are staying at the La Quinta resort or in the area. Steaks are always great! The cocktail list is fun and the wine if also really good. We dined here for 4th of July and while we have had better service in the past, the food and overall was great!
It was 107 but felt cool in the dry desert heat listening to music on the patio. Our wait staff of Javier, Eduardo and Brandon always make the evening special. My wife had the salmon dinner and I had the barbecue chicken quinoa bowl with Seghesio Zinfandel wine. Both were delicious.
We enjoyed a late dinner, 7 pm, on the patio and even though it was late June we were very comfortable. The patio is in the shade and we had the extra benefit of listening to live music coming from the Palm Plaza. The ambiance is to live for. I enjoyed a chicken salad with barbecue flavor it was light and refreshing. I can't remember what my wife had and as she is asleep as I write this I'll have to get back to you. We did enjoy a bottle of Seghesio Zinfandel.
Reasonable menu selection. The items we ordered were very good. Service was very slow. Had to flag down servers for both wine and the bill. Appeared to be a staffing problem rather than a poor server.
Overall it was just ok. We made a reservation for father's day brunch at 11am, and as soon as we walked in we were informed they were no longer serving brunch... is that ok? Well, no but what are my options? I have 2 little kids with me and it's father's day, so we're pretty much stuck here. Drinks were good server was very nice. They brought the kids food out right away which was great. My husband ate the scraps of the brunch buffet that were still out and I ordered a salad off the lunch menu. We waited 15-20 minutes at after the kids food was delivered for the salad to come out and asked 3 people before it was brought out and i'm not really sure if it was the salad I ordered. But, it was good and it was way too late to send it back.
It's heating up in the desert fortunately Twenty Six is in the shade. I had filet mignon cooked medium rare with mushroom sauce-perfect! My wife had the salmon from the entree menu and she complimented the sauce. Brandon provides excellent service and brought us a new Zinfandel- Grgrich and it was excellent with a taste of chocolate at the finish. We had vanilla ice cream, tasted home made, with coffee. We came later at 7 pm to beat the heat and the music on the Palm Plaza was in full swing. Another great evening.
Food was terrible. Complained about the lemonade (if you can believe even the lemonade was terrible) tasting artificial and they brought the gallon plastic jug to the table ! Calamari was frozen and then deep fried, just can't say how disappointed we were in food, service and the over all look of the place .

subset: commoncrawl


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What's the Best True Air Purifier 2018 - Buyer's Guide
Home » Cooling and Air Quality »
Picking the true air purifier that will suit you the most is pretty hard giving the number of manufacturers on the market. Dozens of companies compete for your money! With our help, you can save some time and choose the right true air purifier much faster.
Our Pick: Best True Air Purifier of 2018
|Name and Features
|1. Purezone 3-in-1 True Hepa Air Purifier (Editor's Choice)
Uv-c light safely destroys micro-organisms such as germs, viruses, bacteria, and fungi.
|Read reviews
|2. Germguardian Air Purifier (Best Performance for the Price)
Genuine replacement filter for germguardian air purifier models ac4300bptca, ac4900ca, ac4825, ac4850pt, pureguardian model ap2200ca and black+decker bxap148.
|Read reviews
|3. Desk Air Purifier
Multiple layers true hepa filter.
|Read reviews
|Pure Enrichment
|8.45 pounds
Purifies the air: true hepa filter captures 99.97% of dust, pollen, pet dander, smoke, mold spores, and household odors. Easy & efficient operation: sets up in seconds for immediate use out of the box and features an optional automatic timer that shuts off the unit after 2.4, or 8 hours of continuous use to promote energy efficiency. What you get: air purifier.3-in-1 hepa filter, user manual, industry-leading 5 year warranty, caring customer support 7 days a week, and the peace of mind that comes from a trusted brand with millions of customers worldwide. Destroys germs & bacteria: uv-c light safely destroys micro-organisms such as germs, viruses, bacteria, and fungi.
Whisper-quiet operation: with a noise level at just 30db, purezone silently sanitizes the air for easier breathing and more restful sleep.
What warranty should be offered with a decent true air purifier?
In the most cases, two-year long warranty period is considered as optimal for true air purifier. true air purifierhave a tendency to lose their quality with time. Replacing old true air purifierwith a new model is a much better option than an overpriced lifetime warranty.
|Guardian Technologies
|15.8 x 4.8 x 1.3 inches
|9.6 ounces
Multiple levels of cleaning include hepa, pre-filter and a charcoal layer to help improve indoor air quality. This is a genuine germguardian filter. It is important to only use genuine guardian technologies replacement parts to maintain product performance and warranty. All parts that are not genuine will void the warranty. Only one single combination filter needs to be replaced every 6-8 months depending on the use of the product. Genuine replacement filter for germguardian air purifier models ac4300bptca, ac4900ca, ac4825, ac4850pt, pureguardian model ap2200ca and black+decker bxap148. True hepa filter captures 99.97% of dust and allergens as small as .3 microns such as household dust, pet dander, mold spores and plant pollens. Charcoal filter reduces common odors from pets, smoking and cooking.
|5.9 x 5.7 x 11.9 inches
|1.55 pounds
– only 34db volumes air purifier, hardly can hear the sound. Irregular blades design, noises interaction, reverse offset, so as to achieve a silent effect. Make you feel like in the peaceful nature and breath the most fresh air. Even put it in your night table, you won't be bothered when you're sleeping. And the fresh air it brings you make you sleep better. 27 days consumes 1 kilomatt hour. – converter motor of this air cleaner, super low energy consumption. Every hour consumes 1.5w of electricity. So it can also using in the car. Except the car, it can be uses in the bedroom, office. Just make it near to you, make the purification effect maximize. No matter the office, bedroom or car, let the the air purifier bring you a fresh space. Multiple layers true hepa filter. Absorbed 99% air impurities effectively. – multiple layers of filter net made your healthy guardian. The outer hepa layer, filter all kinds of dust, pollen and allergy source. Capturing the dust above 0.5 micron and aerosol particles. The middle activated carbon granules layer can absorb various harmful substances, including many odor, formaldehyde, toluene.
– this oapier air purifier got small size and light-weight, you are supposed to take it to anywhere you want. Protect your health all the time. Converter motor support super strong power.360 degree circular duct design for the in and out of wind, and hepa composite filter core, accelerated the ventilation and air purification. High-speed emptying the internal air, forming a strong suction, easily absorbing the air dust.
What should be my main choice criteria when buying a true air purifier?
One of the most important factor of any true air purifier is its material. It has to be durable and easy to clean. If you want to find a true air purifier that will serve you for many years, you will have to buy an expensive model made out of the best materials.
I am wondering if buying a true air purifier online is safe
Buying true air purifieronline is absolutely safe! In fact, it might be even safer than buying them in a local store, since you do not need to leave your house. Moreover, if you get a malfunctioning item you can always get a refund or a replacement.
What exactly did you take into consideration while making the list of the best true air purifier?
We considered so many factors that it is nearly impossible to tell you about all of them. Believe us, we did not forget about anything. Price, material, user score, and other characteristics of true air purifierwere used to create this TOP list. We tried our best to help you choose the best true air purifier!
How did you create this rating list with the best true air purifier?
During the creation of this buying guide, we had to look through hundreds of true air purifier. Our team compared many products from various brands in order to find the most optimal model with the best price to quality ratio. The goal was to determine true air purifierthat offer the most value for their money, and we think that we have achieved it.
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Review 1-year UPDATE Weber 46110001 Spirit E210 LP 2-burner grill
Review Qcandles vs Luminara candles - Q candles
Review - ViewTV AT-263 Digital Converter Box


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Kala KA-15-T BNDL
$111 €100 Excluding VAT, shipping costs extra
Info Item number: 470279
- This product is in stock and can be shipped immediately.
- Item number: 470279
- sales unit: 1 piece
- available since: 2019/07/22
- The prices in € are a guideline only.
Product Details
Ukulele Starter Kit
- Body size: Tenor
- Top: Mahogany (Entandrophragma cylindricum)
- Bottom and sides: Mahogany (Entandrophragma cylindricum)
- Neck: Mahogany (Entandrophragma cylindricum)
- Nut and saddle: GraphTech NuBone
- Fretboard: Black walnut
- Scale: 431 mm
- Total length: 662 mm
- 18 Brass frets
- Open translated machine heads
- Bridge: Black walnut
- Aquila Super Nylgut strings
- Chrome hardware
- Finish: Silk-matte
- Colour: Natural
- Includes padded bag with Kala logo, Kala Klipz chromatic clip-on tuner, black Kala strap and Aquila Bionylon string set
Note: Register your product at www.w-distribution.com/Warranty to extend the warranty to 4 years.
Sales Rank
Customers Interested in This Product Also Bought
32% bought this product
Kala KA-15-T BNDL
In stock


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Winter Wonderland at the Hard Rock Hotel London
Spend your day exploring London's Winter Wonderland, one of the most popular attractions that London has to offer at this time of year. The winter fair, at Hyde Park is just steps from Hard Rock Hotel London and is attended by millions every year. It has many rides and holiday inspired villages for children and adults of all ages.
After a full day out, warm up in our cosy Cafe complete with a limited time 2 course Festive Menu, and our traditional English breakfast the next morning.
Enjoy a perfect nights sleep in our super comfy Hypnos beds, which is ideal after a full day of activities!
Cancel by 2 PM local time, day of arrival to avoid penalty charges
Credit card guarantee required at time of booking.


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|Bedrooms 0
|Parking Spaces 0
Residential unit in the heart of downtown Barrie. 17 foot ceilings, bachelor, open concept kitchen. Perfect for those looking to be in the heart of downtown. Close to all amenities, waterfront, bus station, public parking, restaurants, banks, etc. (id:18750)
Listing Office: Ed Lowe Limited Brokerage
Data Provided by REALTORS® Association of Canadian Real Estate
Last Modified: Fri, 29 Nov 2019 15:25:54 GMT
MLS®, REALTOR®, and the associated logos are trademarks of The Canadian Real Estate Association
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Address: Shop 54 Mountain Gate Shopping Centre, Ferntree Gully VIC 3156
Book Direct with the Owner at Jacks Place with Accommodation Australia in Ferntree Gully, for all your restaurant and Food Reservations.
Accommodation Australia welcomes Jacks Place in Ferntree Gully VIC 3156, we provide a friendly relaxing restaurant and bar. Jacks Place is a great place to unwind with a cold drink, an ideal place to watch and forget about the hustle and bustle while you enjoy a freshly brewed coffee or a snack from our affordable specials menu.
Is Jacks Place in Ferntree Gully your property on Accommodation Australia, please claim your listing and subscribe to update your contact details and receive your phone calls and emails from your clients.
copyright © 2019 Accommodation Australia. All rights reserved.


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If you find our thought pieces on brand strategy and brand management insightful and would like a deeper understanding for yourself, your marketing teams or leadership teams we can develop a customized learning and development engagement for you.
As a brand licensing strategist I spent five years at the NBA, which in addition to basketball was known as 'Nothing But Attorneys'. Fortunately those attorneys were fantastic in-house counsel to whom we had access, and they were happy to pass on their knowledge – especially to those who were prepared, eager to learn and understood the importance of protecting the collective intangible assets of the NBA.Read More
Companies have sales strategies for their products and distribution. Brand and product messaging rely on content and flow. Today that includes television advertising and the various forms of social media available on multiple devices.Read More
Bad behavior is why clear contract terms are critical to the success of a brand and celebrity licensing partnership. As Benjamin Franklin once said, "It takes many good deeds to build a good reputation, and only one bad one to lose it."Read More
If it looks like a duck, swims like a duck, and quacks like a duck, then it probably is a duck. This test implies that a person can identify an unknown subject by observing that subject's habitual characteristics.Read More
Pharmaceutical companies make substantial marketing investments across the life cycles of their products to build brand power and value in the market. As a result, today's major pharmaceutical companies have significant equity tied to their brands, making them valuable assets. Layer on positive consumer relationships, said asset takes on even greater value.Read More


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Sexy Dark Chocolate: This Chick Looks Really Good In Her Lingerie!
Uploaded June 10, 2018
Posted By Ghost
Well That Was Embarrassing: Little Dude Gets Manhandled By His Girl For Coming Home At 4 am!
Wait For It: This Chick Is Out Here Living Her Best Life!
Best Selling Author Explains Why They Don't Teach You About Money In School!
Triggered: Girl Pulls A Gun On Her Boyfriend After Finding Some Chick's Panties In Her Bed!
What Is This? Chick Does A Dance In Which It Looks Like She Sucking Multiple D*cks!
Some Conspiracy S**t: Footage Resurfaces of Juice Wrld Doing Final Ritual, Selling His Soul & Joining Illuminati During Video Shoot!
Group Of Guys Get Instant Karma After Trying To Intimidate & Steal Pizza From Delivery Without Paying! (Rewind Clip)
Dark Thick Chocolate: This Instagram Model Has A Nice Glow!
Former Kentucky Governor Pardons Hundreds Of Violent Inmates After Losing Election!
Oh My: This Chick Got The Best Job In The World!
Drug Addiction Is No Joke: Rapper Juice Head Pops 10 Pills On Camera!
This Chick Is Crazy: Lady Tries To Break A Car Windshield With A Knife To Attack Her Man!
Jit Was Going To Slice His Brother Over A Slice Of Pizza! "You Gonna Kill Me Over Some Pizza?!"
Epitome Of Entitlement: This Lady Is Really Holding Up Traffic In NY On Some Petty Sh*t!
This Man Is Really Having A Bad Day!
Can't Hit Other People's Kids: Lady Pulls Up On Daycare Teacher's Home After Finding Out She Slapped Her 13-Year-Old Daughter!
Real Life Cujo: This Dog Looks Like Something Out Of A Horror Film!
Ya'll Feeling The Design? Microsoft's Next Console For 2020 Is The Xbox "Series X"
Women Can Do This Chair Challenge That Men Cannot Do!
He Knows How To Pick Em: Drake Was Out Spotted With This Chick & Her Body Is Crazy!
Jose Guapo Wasn't Here For All These Big Words! "You Tryin To Be T.I. And S**t"
He Gone Have Nightmares After This: Kid Goes On A Horse & Instantly Regrets It!
Sexy Chick Breaks A Watermelon Between Her Legs!
Took Xmas Into Their Own Hands: These Kids Used Their Mother's Credit Card To Order $700 Worth Of Toys!
WTF: This Chick Has A Very Weird Looking Belly Button!
WTF: You Won't Believe What This Chick Wants From Man On Live!
She's Not Playing: Mother Goes Off On A Girl Who Tried To Fight Her Daughter! "You Fat B***h, What You Gonna Do?"
Hilarious: When You And Your Boy Run A Train On Thot & He Putting In More Work Than You! [Skit]
Nick Cannon Feat. Suge Knight, The Black Squad & Prince Eazy - The Invitation (Eminem Diss)
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Follow me on Instagram!The intimate struggle and yet at the same time the intricate dance between Karen Carpenter's creative expression and her mental state is powerful in her chart, one of my sample readings in the upcoming 2nd expanded edition of Shedding Light on Jyotisha, Vedic Astrology for Beginners. 🌟 #karencarpenter #thecarpenters #celebritybirthchart #sheddinglightonjyotisha #vedicastrology #jyotish #jyotishastrologyDaily Tarot Insight for Wednesday December 11, 2019 - The Nine of Vessels, Generosity - Each and every one of us has within an unfillable vessel called the heart, that has an infinite abundance of compassion and kindness to give to others. Dip deeper into this vessel today. ❤ Deck: The Wildwood Tarot ❤ #thewildwoodtarot #heart #compassion #kindness #bekindtooneanother #kindnessmatters #dailymotivation #dailyinspiration #infinitelove #lifecoachinghappiness
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Tag Archives: Surrender
What Is Forgiveness?
Originally posted on Blazing Light of Glory:
Since completing the last review section, lessons 201-220, The Course has taken a change of course in how it presents the lessons. They are now broken down into sections of ten lessons with a topic…
Posted in Meditations Tagged a course in miracles, ACIM, Forgiveness, God, I Am, illusion, letting go, Love, peace of God, reality, stillness, Surrender, Truth 1 Comment
The Second Limb of Yoga: Tapas, Ishvara Pranidanam, & Svadhyaya
The other three observances of Niyama, the … Continue reading
Posted in Yoga Tagged austerity, bhakti, devotion to God, ishvara pranidanam, mantra, mendicant, niyama, self-awareness, self-study, shastra, Surrender, sutra, svadhyaya, tapas, yoga Leave a comment
The Four Noble Truths: The Truth to The Cessation of Suffering (Nirodha)
If we choose to become spiritual warriors, how will … Continue reading
Posted in Religions & Philosophies Tagged Buddha, compassion, Four Noble Truths, Freedom, Hafiz, Love, practice, Rabia, Saint Francis of Assisi, Sufi, Surrender, Tibetan medicine, True Self, wheel of life Leave a comment