text: Lidocaine Impairs Proliferative and Biosynthetic Functions of Aged Human Dermal FibroblastsBentov, Itay MD, PhD*; Damodarasamy, Mamatha MS†; Spiekerman, Charles PhD‡; Reed, May J. MD†Anesthesia & Analgesia: September 2016 - Volume 123 - Issue 3 - p 616-623 doi: 10.1213/ANE.0000000000001422 Preclinical Pharmacology: Original Laboratory Research Report Free Abstract Author InformationAuthors Article OutlineOutline Article MetricsMetrics BACKGROUND: The aged are at increased risk of postoperative wound healing complications. Because local anesthetics are infiltrated commonly into the dermis of surgical wounds, we sought to determine whether local anesthetics adversely affect proliferative and biosynthetic functions of dermal fibroblasts. We also evaluated the effect of local anesthetics on insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1), growth factors that are important regulators of wound healing. METHODS: Human dermal fibroblasts (HFB) from aged and young donors were exposed to local anesthetic agents at clinically relevant concentrations. We screened the effects of lidocaine, bupivacaine, mepivacaine, and ropivacaine on proliferation of HFB. Lidocaine was most detrimental to proliferation in HFB. We then evaluated the effect of lidocaine on expression and function of the growth factors, IGF-1 and TGF-β1. Lastly, concurrent exposure to lidocaine and IGF-1 or TGF-β1 was evaluated for their effects on proliferation and expression of dermal collagens, respectively. RESULTS: Lidocaine and mepivacaine inhibited proliferation in aged HFB (for lidocaine 88% of control, 95% confidence interval [CI], 80%–98%, P = .009 and for mepivacaine 90% of control, 95% CI, 81%–99%, P = .032) but not in young HFB. Ropivacaine and bupivacaine did not inhibit proliferation. Because of the clinical utility of lidocaine relative to mepivacaine, we focused on lidocaine. Lidocaine decreased proliferation in aged HFB, which was abrogated by IGF-1. Lidocaine inhibited transcripts for IGF-1 and insulin-like growth factor-1 receptor (IGF1R) in fibroblasts from aged donors (IGF-1, log2 fold-change −1.25 [42% of control, 95% CI, 19%–92%, P = .035] and IGF1R, log2 fold-change −1.00 [50% of control, 95% CI, 31%–81%, P = .014]). In contrast, lidocaine did not affect the expression of IGF-1 or IGF1R transcripts in the young HFB. Transcripts for collagen III were decreased after lidocaine exposure in aged and young HFB (log2 fold-change −1.28 [41% of control, 95% CI, 20%–83%, P = .022] in aged HFB and log2 fold-change −1.60 [33% of control, 95% CI, 15%–73%, P = .019] in young HFB). Transcripts for collagen I were decreased in aged HFB (log2 fold-change −1.82 [28% of control, 95% CI, 14%–58%, P = .006]) but not in the young HFB. Similar to the transcripts, lidocaine also inhibited the protein expression of collagen III in young and aged HFB (log2 fold-change −1.79 [29% of control, 95% CI, 18%–47%, P = .003] in young HFB and log2 fold-change −1.76 [30% of control, 95% CI, 9%–93%, P = .043] in aged HFB). The effect of lidocaine on the expression of collagen III protein was obviated by TGF-β1 in both young and aged HFB. CONCLUSIONS: Our results show that lidocaine inhibits processes relevant to dermal repair in aged HFB. The detrimental responses to lidocaine are due, in part, to interactions with IGF-1 and TGF-β1. From the *Department of Anesthesiology and Pain Medicine and †Division of Gerontology and Geriatric Medicine, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, Washington; and ‡Center for Biomedical Statistics, Institute for Translational Health Sciences, University of Washington, Seattle, Washington. Accepted for publication April 27, 2016. Funding: This work was supported by the National Institute of Aging, Bethesda, MD (R03 AG042353 to I.B.). This project was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000423. The authors declare no conflicts of interest. Address correspondence and reprint requests to Itay Bentov MD, PhD, Department of Anesthesia and Pain Medicine, University of Washington, Harborview Medical Center, 325 9th Ave, Box 359724, Seattle, WA 98104. Address e-mail to email@example.com. Abstract METHODS Cell Lines Local Anesthetics Cell Proliferation Assays Expression of Transcripts IGF-1 Stimulation Crystal Violet Staining TGF-β1 Stimulation Western Blots Statistical Analysis RESULTS Local Anesthetics Are Variable in Their Effect on HFB Proli... Lidocaine Affects Transcription in Aged HFB to a Greater Ex... Lidocaine Inhibits Proliferation in Aged HFB, an Effect Tha... Lidocaine Inhibits the Expression of COL III in Both Young ... DISCUSSION DISCLOSURES ACKNOWLEDGMENTS REFERENCES Disrupted surgical wound healing is common (about 500 000 cases annually in the United States) and leads to poor patient outcomes and excess costs.1 Impaired surgical wound healing is particularly a problem in the older population, who are at increased risk of wound dehiscence and infection.2 Dysregulation of growth factors, which is further compromised during the response to stress, is one of the features of poor healing in older hosts.3 For example, in an aged mouse model, deficits in growth factor expression contributed to delayed cutaneous wound healing.4 Although there are many cell types in the skin, fibroblasts are the primary cell responsible for both proliferation and biosynthesis of extracellular matrix (ECM) in the dermis. Dermal fibroblasts are used commonly to elucidate many of the mechanisms of impaired wound healing in aging. These cells are an accepted model for studies of dermal wound healing5 and, specifically, of age-related changes in cutaneous wound healing.6 Cellular replication and deposition of ECM often are reduced in aged dermal fibroblasts when studied in vivo and in vitro.7 Punch biopsies obtained repeatedly over the life span of hamsters found that in vitro proliferative capacity of dermal fibroblasts mimicked in vivo dermal wound repair.8 Proliferation and biosynthesis in the dermis are modulated by the expression and activity of growth factors that are altered with aging, such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1).9 IGF-1 is a mitogenic factor for cells and promotes the interaction of dermal fibroblasts with the ECM during tissue injury and repair.10,11 Synthesis of IGF-1,12 and the expression of its cognate receptor, insulin-like growth factor-1 receptor (IGF1R), by fibroblasts is an essential determinant of proliferation in the dermis.13 Decreased proliferative capacity of aged dermal fibroblasts is associated with reduced IGF-1 and IGF1R expression and activation.14 The fibrogenic growth factor TGF-β1 is highly expressed in connective tissue, but its expression decreases with aging.15 A lack of TGF-β1 results in less deposition of ECM proteins, such as the interstitial collagens III and I (COL III and COL I, respectively) that comprise the majority of the dermal ECM. Treatment of cutaneous pain by local anesthetic agents is used by many medical specialties. There is a wide spectrum of treatment regimens for local anesthetics; from short procedures that use local infiltration to treatment of postoperative pain or complex pain syndromes in which skin patches and subcutaneous infusions are used for days.16,17 Although the prolonged use of local anesthetic (lidocaine) dermal patches is indicated only on intact skin and the use of local anesthetic agents is considered relatively safe, in vitro and in vivo studies have suggested a potential detrimental effect on any wounds that are undergoing healing.18 Previous studies have shown that local anesthetic agents are toxic to neural and muscle tissues in a concentration- and agent-specific manner.19,20 It has been suggested that local anesthetics have an adverse effect on wound repair by delaying the synthesis of collagens21 and/or by an antiproliferative effect on mesenchymal cells.22 In this study, we used primary dermal fibroblasts obtained from aged and young human donors to test the hypothesis that local anesthetics affect proliferative and biosynthetic functions that are important for cutaneous wound healing. Back to Top | Article Outline METHODS Cell Lines On the basis of our previous data14 with respect to expected effect size and standard deviation of the outcome, using a power of 0.8 (β) and significance set at 0.05 (α, 2-tailed), we needed 3 to 4 samples each of young and aged human dermal fibroblasts (HFB) to find differences in proliferation. Early passage HFB lines from 4 healthy aged male donors (mean age = 83 years), AG04152 (83 years), AG04383 (80 years), AG04057 (81 years), and AG04064 (92 years) referred to as "aged HFB" and 4 healthy young male donors (mean age = 28 years), AG11747 (22 years), AG11242 (30 years), AG05415 (29 years), and AG10046 (31 years) referred to as "young HFB," were obtained from the Coriell Institute (NIA Aging Cell Repository, Coriell Institute for Medical Research, Camden, NJ) and cultured in Dulbecco's Modified Eagle Medium (DMEM) with 5% fetal bovine serum (FBS) (Cellgro, Manassas, VA). Unless otherwise noted, each cell line was studied individually and each experiment was repeated 3 times. All experiments were performed in DMEM with 1% FBS.23 To establish their phenotype, all cell lines were examined for morphology, staining for senescence-associated β-galactosidase, and expression of the cell-cycle inhibitors p16 and p21. To determine whether the cells' phenotype corresponded to the chronological age of their donor, cell lines were ranked in order from highest to lowest for each marker of aging, and each line was given an average rank score as we have previously described.14 Initial screenings of the 4 local anesthetics were done on 6 HFB cell lines (3 aged HFB and 3 young HFB); further experiments were performed on 8 HFB cell lines (4 aged HFB and 4 young HFB). Back to Top | Article Outline Local Anesthetics We used concentrations of local anesthetics similar to that previously published using human fibroblast cell lines.24 In a separate study, similar concentrations of local anesthetics were not cytotoxic to human oral fibroblasts.25 It should be noted that an important determinant of tissue concentration of local anesthetics is dermal blood flow,26 which is highly variable and results in contiguous dermal regions being exposed to a wide range of local anesthetic concentrations. To approximate the exposures that dermal fibroblasts typically see in vivo, we extrapolated from existing studies in animal models. As an example, a pharmacokinetic model in the rat suggests that the penetration of lidocaine is up to a depth of 1 cm below the skin and occurs predominantly during the first 2 hours.27 For the purpose of this study, we assumed that because of systemic uptake and incomplete penetration, approximately 5% of the local anesthetic reaches the dermal fibroblasts. Therefore, we diluted the local anesthetics to expose the fibroblasts to a final concentration of 1/20 of clinically available local anesthetics. The final concentration of local anesthetics used in all the assays are lidocaine 1% (Hospira Inc, Lake Forest, IL) and mepivacaine 1% (Fresenius Kabi USA, Schaumburg, IL) at a final concentration of 500 μg/mL, bupivacaine 0.25% (Hospira Inc), and ropivacaine 0.5% (Fresenius Kabi USA) at a final concentration of 125 μg/mL. Normal saline, at the same volume as the local anesthetic, served as the control in all experiments. Back to Top | Article Outline Cell Proliferation Assays For screening of different local anesthetics, we chose 6 HFB cell lines; 3 young (AG11747, AG11242, and AG10046) and 3 aged (AG04064, AG04383, and AG04152) for individual experiments based on consistent alignment with a young and aged phenotype, respectively, as previously described.14 HFB cell lines were plated at subconfluence in 5% DMEM in triplicate in 96-well plates (5000 cells/well). Cells were allowed to adhere for 6 hours and were then serum-deprived with DMEM 1% FBS overnight. The following day, cells were exposed to saline or a local anesthetic. Twenty-four hours later, all media were changed to 1% DMEM, and proliferation was measured after 48 hours with the CellTiter 96 AQueous One Solution Cell Proliferation Assay (Promega, Madison, WI). Back to Top | Article Outline Expression of Transcripts Four young and 4 aged HFB cell lines were plated in 5% DMEM in 6-well plates (Corning, Tewksbury, MA) at 75% confluence for 6 hours. Media were then changed to 1% DMEM overnight. The next day cells were exposed to lidocaine (500 μg/mL), bupivacaine (125 μg/mL), or normal saline (carrier) in 1% DMEM. RNA was isolated from cells after 3, 6, and 18 hours by the use of TRIzol (Invitrogen). RNA purity and integrity were assessed by spectrophotometric analysis. A total of 1 μg of RNA was reverse transcribed using an iScript kit (Bio-Rad Laboratories, Hercules, CA). Reverse transcription polymerase chain reaction (RT-PCR) was performed with an ABI 7900 RT-PCR instrument with SYBR Green Master Mix (Bio-Rad) for human IGF-1, IGF1R, COL I, COL III, and TGF-β1. The following primer sequences were used: IGF-1 F: GGACCGGAGACGCTCTGC IGF-1 R: AGCTGACTTGGCAGGCTT IGF1R F: CCATTCTCATGCCTTGGT IGF1R R: TGCAAGTTCTGGTTGTCG COL I F: GTGCTAAAGGTGCCAATGGT COL I R: ACCAGGTTCACCGCTGTTAC COL III F: CCAGGAGCTAACGGTCTCAG COL III R: CAGGGTTTCCATCTCTTCCA TGF-β1 F: TCCGGTTTGATCTTTCCAAG TGF-β1 R: ATCCGGAACGTCTCATTGTC Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) F: GGCCTCCAAGGAGTAAGACC GAPDH R: AGGGGTCTACATGGCAACTG All experiments were performed in triplicate and normalized to GAPDH messenger RNA (mRNA). Fluorescent signals were analyzed during each of the 40 cycles consisting of denaturation (95°C, 15 seconds) and annealing (54°C, 15 seconds). Relative quantitation was calculated by use of the comparative threshold cycle method, and data are shown as average fold-change for lidocaine from control. Back to Top | Article Outline IGF-1 Stimulation To determine the optimal concentration of IGF-1 to induce proliferation, preliminary experiments were performed on a subset of young and aged HFB. HFB were placed in low serum conditions (DMEM + 1% FBS) for 6 hours and were then exposed to recombinant human IGF-1 at 10, 50, and 100 ng/mL (R&D Systems, Minneapolis, MN) for 24 hours. The concentration of IGF-1 that was optimal for proliferation after 48 hours (as determined by the proliferation assay described earlier) was determined to be 50 ng/mL. The effects of lidocaine with and without IGF-1 were performed on 4 young and 4 aged HFB. Back to Top | Article Outline Crystal Violet Staining Representative young and aged HFB cell lines were plated in 5% DMEM on 10-well Teflon-masked microscope slides (5000 cells/well; Creative Scientific Methods, Phoenix, AZ) for 6 hours, and cells were serum-deprived with 1% DMEM overnight. The following day, cells were exposed to lidocaine or saline with or without IGF-1 for 24 hours, and media were changed to 1% DMEM. After 48 hours, cells were fixed in 10% neutral buffered formalin (NBF) stained with 0.1% crystal violet, and imaged using light microscopy. Back to Top | Article Outline TGF-β1 Stimulation Aged and young HFB were placed in low serum conditions overnight (1% DMEM) and then exposed to saline or lidocaine with or without recombinant human TGF-β1 (10 ng/mL; R&D systems). The concentration of TGF-β1 was based on previous work in which these cell lines were used.28 Protein was isolated from the cells and Western blotting completed as described below. Back to Top | Article Outline Western Blots Four young (AG11747, AG11242, AG10046, and AG05415) and 4 aged (AG04064, AG04383, AG04152, and AG4057) HFB cell lines that were used for the proliferation assay were plated in 5% DMEM in 6-well plates for 6 hours and then serum-deprived overnight with 1% DMEM. The following day, cells were exposed to saline or lidocaine with or without TGF-β1. All media were changed to 1% DMEM after 24 hours of exposure, and cell lysates were collected after 48 hours. Cells were lysed in NP40 buffer with protease and phosphatase inhibitors (Sigma-Aldrich, Saint Louis, MO). Lysates were prepared for electrophoresis as described.29 Equal amounts of protein were subjected to 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by transfer to nitrocellulose. After incubation with 5% milk, blots were probed with antibodies (1–5 µg/mL) against COL III (Abcam, Cambridge, MA), COL I (Abcam), and GAPDH (Millipore, Billerica, MA). Back to Top | Article Outline Statistical Analysis As expected, there was variability among cell lines within each group (young and aged donors). Accordingly, for each cell line, our results indicate differences relative to the cell line-specific controls. Within each age group, we determined whether the active treatments differed from controls by using a linear model on the log2-transformed outcomes with condition entered as a fixed effect and cell line as a random effect. Residuals were assessed, and no obvious departures from normality and variance homogeneity assumptions were noted. Within each age group and each outcome, multiple conditions were compared with controls and adjustments for possible type I error were included in the analyses. The Dunnett method for multiple comparisons was utilized in the analyses in which the design was completely balanced. When the design was imbalanced, the Bonferroni method was used. Statistical significance was defined by P < .05, and biological significance was defined as a change of 10% or greater. Back to Top | Article Outline RESULTS Local Anesthetics Are Variable in Their Effect on HFB Proliferation Figure 1. We tested the hypothesis that exposure to local anesthetics inhibits proliferation of dermal fibroblasts. Bupivacaine and ropivacaine did not inhibit proliferation of dermal fibroblasts in the aged HFB or in young HFB (Figure 1). Lidocaine and mepivacaine inhibited proliferation in aged HFB (for lidocaine 88% of control, 95% confidence interval [CI], 80%–98%, P = 0.009 and for mepivacaine 90% of control, 95% CI, 81%–99%, P = .032). Lidocaine did not inhibit proliferation in young HFB to a biologically significant degree (94% of control, 95% CI, 90%–99%, P = .027 in young HFB), and mepivacaine did not inhibit proliferation in young HFB (97% of control, 95% CI, 92%–102%, P = .3; Figure 1). Further studies focused only on the specific effects of lidocaine for the following two reasons. First, lidocaine inhibition of proliferation had the largest effect on aged fibroblasts. Second, lidocaine is commonly used for both short procedures and prolonged infusions. Back to Top | Article Outline Lidocaine Affects Transcription in Aged HFB to a Greater Extent Than in Young HFB Figure 2. We sought to define the effect of lidocaine on the transcription of IGF-1 and IGF1R in dermal fibroblasts from aged and young donors. Each cell line was studied separately, and we calculated the fold-change induced by exposure to lidocaine at 500 μg/mL. Our results show that 18 hours of exposure to lidocaine inhibits transcripts for IGF-1 and IGF1R in the fibroblasts from aged donors (Figure 2, panel B; IGF-1, log2 fold-change −1.25 [42% of control, 95% CI, 19%–92%, P = .035] and IGF1R, log2 fold-change −1.00 [50% of control, 95% CI, 31%–81%, P = 0.014]) but not in the young HFB (IGF-1, log2 fold-change −1.04 [49% of control, 95% CI, 11%–216%, P = .332] and IGF1R, log2 fold-change −0.87 [55% of control, 95% CI, 9%–331%, P = .72]; Figure 2, panel A). Transcripts for COL III and COL I were decreased after lidocaine exposure for 18 hours in aged HFB (for COL III: log2 fold-change −1.28 [41% of control, 95% CI, 20%–83%, P = .022], and for COL I: log2 fold-change −1.82 [28% of control, 95% CI, 14%–58%, P = .006]). In young HFB, lidocaine decreased transcripts for COL III (log2 fold-change −1.60 [33% of control, 95% CI, 15%–73%, P = .019]). Our results did not indicate a statistically significant difference in young HFB with respect to COL I (log2 fold-change −1.95 [26% of control, 95% CI, 5%–125%, P = .076]). Shorter exposures to lidocaine (3 and 6 hours) did not result in significant changes in the expression of IGF-1, IGF1R, COL I, or COL III transcripts (data not shown). Interestingly, lidocaine did not show evidence of change in the average mRNA levels of the profibrotic growth factor TGF-β1 in young or aged HFB (log2 fold-change 0.87 [183% of control, 95% CI, 83%–401%, P = .12] for aged HFB, and log2 fold-change 0.84 [179% of control, 95% CI, 40%–805%, P = .54] in young HFB), but there was a variable response among cell lines in each group. Exposure of aged HFB to lidocaine did not change the expression of transcripts for epidermal growth factor, the epidermal growth factor receptor, or basic fibroblast growth factor (data not shown). Back to Top | Article Outline Lidocaine Inhibits Proliferation in Aged HFB, an Effect That Is Abrogated by IGF-1 Figure 3. We then tested the hypothesis that lidocaine exposure inhibits proliferation of HFB and that this effect is abrogated by treatment with IGF-1. As shown by representative crystal violet staining photographs of dermal fibroblasts from an aged donor AG04383 (Figure 3, panel A), exposure to lidocaine reduces the number of viable cells. As expected, the proproliferative growth factor IGF-1 increased the number of cells such that proliferation was not visually different from control when IGF-1 was coadministered with lidocaine. For quantification of proliferation, we show the results from 4 separate young cell lines and 4 aged cell lines (Figure 3, panel B). We found that lidocaine reduced proliferation in aged HFB (76% of control, 95% CI, 66%–81%, P < .0001 gray bars) to a greater extent than in young HFB (89% of control, 95% CI, 75%–106%, P = .25, black bars). Exposure to IGF-1 alone did not significantly increase proliferation, relative to control, in either young or aged HFB. When given concurrently, the addition of IGF-1 abrogated the inhibitory effect of lidocaine on proliferation in aged HFB. Back to Top | Article Outline Lidocaine Inhibits the Expression of COL III in Both Young and Aged HFB, an Effect That Is Abrogated by TGF-β1 As noted previously, lidocaine had a variable effect on transcripts for the profibrotic growth factor, TGF-β1. To test whether lidocaine inhibits the biosynthesis of key dermal structural proteins, we used RT-PCR and Western blotting to assess the transcription and expression of COL III and COL I. Our results show that lidocaine significantly inhibits the transcription of COL III in both young and aged HFB and inhibits COL I in aged HFB (discussed earlier, Figure 2). Of note, exposure of aged HFB to lidocaine did not change the expression of the ECM protein fibronectin (P > .3, data not shown). Figure 4. Figure 4, panel A, shows a representative Western blot of an aged (AG04383) cell line for COL III and COL I. Densitometric analysis of individual experiments from 4 young (Figure 4, panels B and C, black bars) and 4 aged cell lines (Figure 4, panels B and C, gray bars) demonstrated that lidocaine inhibits the expression of COL III in young and aged HFB (log2 fold-change −1.79 [29% of control, 95% CI, 18%–47%, P = .003] in young HFB and log2 fold-change −1.76 [30% of control, 95% CI, 9%–93%, P = 0.043] in aged HFB). The expression of COL I was not affected by lidocaine in the young cell lines (log2 fold-change −1.33 [40% of control, 95% CI, 2%–857%, P = .72]). Despite its effects on COL I transcripts, lidocaine did not alter the expression of COL I protein in aged HFB in a statistically significant fashion (log2 fold-change −1.45 [37% of control, 95% CI, 12%–110%, P = .064]). As expected from other model systems,30 exposure to TGF-β1 had little effect on the expression of COL III and COL I in both young and aged HFB. However, TGF-β1 obviated the inhibitory effect of lidocaine on COL III expression, in both young and aged HFB (Figure 4, panel B). Back to Top | Article Outline DISCUSSION Proliferation and biosynthesis are key functions during all stages of wound healing. It generally is accepted that both processes are reduced in the dermis with aging and contribute to the 30% to 40% delay in wound healing that is seen in aged hosts.31 Reduced production of autocrine and paracrine growth factors contributes, in part, to delayed wound repair in aging.32 Indeed, manipulation of growth factors continues to be investigated as a treatment modality to improve wound healing in older persons.33 Local anesthetic agents have been shown to affect the viability and function of various cells and tissues, including chondrocytes, nucleus pulposus cells, corneal endothelial cells, neurons, and rodent wounds.19,34–36 In this study, we hypothesized that local anesthetics at concentrations that represent exposure of dermal fibroblasts during skin infiltration could negatively impact cellular functions that are important for wound repair. It is understood that in vitro findings often form the basis for concerns of toxicity but need to be confirmed in vivo.37 Previous work on the toxicity of local anesthetics has been studied primarily in neuronal cells. Mechanisms of toxicity of different local anesthetic agents are varied and include impacts on sodium channels, mitochondrial functions,38 and inflammatory responses.39,40 For screening purposes, we chose 4 agents with widespread utility in clinical practice. Our results suggest that lidocaine and mepivacaine inhibit proliferation in aged HFB, whereas bupivacaine and ropivacaine do not. Although the magnitude of the effect is relatively small (about 10%–25%), given that wound healing is reduced by 30% to 40% in aging, a decrease of 10% to 25% in proliferation could constitute a clinically significant contribution to age-associated deficits in dermal repair. To our knowledge, the connection between IGF-1 or TGF-β1 and local anesthetic agents has not been examined previously. We hypothesized that the effect of lidocaine on aged HFB is mediated (at least in part) by regulating the expression of growth factors that are implicated in the aging process and participate in dermal repair, such as IGF-1 and TGF-β1. The role of the IGF-1/IGF1R axis in aging and longevity is well established in humans, as well as in model systems from a range of biologic phyla.41 Up-regulation of IGF-1 is observed within days after various insults such as hypoxic-ischemic brain injury, brain contusion, and penetrating trauma.42–44 Moreover, IGF-1 (produced mostly by dermal fibroblasts) is increased after skin injury45 and implicated in animal models of wound healing.46 TGF-β1 is the primary growth factor that regulates collagen deposition and has been implicated in both dermal healing and scarring. It generally is accepted that deposition and remodeling of collagen is slower in aged animals47; however, when dermal HFB from aged donors were exposed to TGF-β1, they showed similar biosynthetic and contractile properties as that of young HFB.28 In this study, the reduction of proliferation in the aged donors was mediated (at least in part) by the IGF-1/IGF1R axis, as lidocaine exposure resulted in a reduction in IGF-1 and IGF1R mRNA transcripts only in the aged HFB. Furthermore, lidocaine-induced reduction of proliferation was abrogated by exposure to IGF-1. Notably, in a neuronal model in vitro, the cytotoxic effects of local anesthetics were not reversed by nerve growth factor.48 The effect of lidocaine on key structural ECM components focused on transcription and expression of COL III, which provides an early provisional matrix, and COL I, which comprises the majority of the structural matrix that maintains dermal integrity.9 Lidocaine decreased transcripts for COL III in both young and aged HFB and for COL I in the aged HFB. Although lidocaine inhibited the transcription of both collagens in aged HFB, the negative impact on the protein accumulation was noted only for COL III. The lack of change in COL I protein likely reflects the high content of COL I in dermal HFB in the control state, thereby limiting the detection of potential lidocaine-induced changes. The accumulation of COL III protein (with its significantly shorter half-life than COL I) would be more susceptible to lidocaine, irrespective of the phenotypic age of the cell line.4 Similar to the effect of IGF-1 on proliferation, the lidocaine-induced reduction of biosynthesis in aged HFB was abrogated by exposure to TGF-β1. It is noteworthy that although there is a trend to an increase in TGF-β1, lidocaine did not significantly alter the transcription of this growth factor. This does not exclude the possibility of significant lidocaine effects on downstream mediators of TGF-β1 activity, such as the SMADs.49 Similar reductions in collagen accumulation after local anesthetic infiltration were observed in aged mice and were accompanied by increased activity of the collagen-degrading enzyme matrix metalloproteinase-2.50 Limitations of this study include the observation that regardless of donor age, dermal fibroblasts lose their chronologic phenotype with respect to replicative capacity when proliferation is measured in vitro.51 In vitro simulation of aging is dependent on its maintaining an aged phenotype in culture. To mitigate this concern, as noted earlier, we used only early passage cells and have previously confirmed that these cells maintain the chronologic phenotype of their donor.14 Moreover, the use of a single cell type (HFB from young and aged male donors) as an in vitro model for dermal function is also a limitation. Wound healing is a complex system, both temporally and spatially, with numerous cell types and effectors. It is likely that lidocaine influences inflammation,52 angiogenesis,53 and other processes that are essential in wound healing but could not be examined in this study. Although we screened 4 local anesthetic agents for their effect on fibroblast proliferation, our experiments focused on lidocaine for reasons noted earlier. Last, the dermal concentrations of local anesthetics have not been measured; we chose a hypothetical concentration for local anesthetic exposure that was similar for both young and aged HFB. Because there is a decrease in the dermal microcirculation in aged skin,54 it is likely that reduced blood flow increases the concentration of local anesthetics by decreasing uptake and subsequent clearance. We propose that age-related deficits in the dermal circulation enhance, rather than reduce, the effect of lidocaine on aged HFB. In summary, we propose that lidocaine inhibits cellular functions in dermal HFB from aged donors, which could impact subsequent cutaneous wound healing. Our results suggest that age-related responses to lidocaine are due, in part, to interactions with IGF-1 and TGF-β1. These key growth factors are altered during normal aging and are necessary for wound repair. It is important to note that the effect of local anesthetic agents on reducing the stress response and alleviating pain could benefit some wound healing responses,55 which might offset the potential deleterious consequences of local anesthetics. Determining the net impact of lidocaine on wound healing responses in aging requires further investigation, similar to research examining the effects of intrathecal lidocaine on neurological injury.56 We encourage additional studies to evaluate wound healing in the elderly after exposure to local anesthetics. Back to Top | Article Outline DISCLOSURES Name: Itay Bentov, MD, PhD. Contribution: This author helped design the study, analyze the data, and write the manuscript. Name: Mamatha Damodarasamy, MS. Contribution: This author helped design the study, analyze the data, and write the manuscript. Name: Charles Spiekerman, PhD. Contribution: This author helped analyze the data and write the manuscript. Name: May J. Reed, MD. Contribution: This author helped design the study, analyze the data, and write the manuscript. This manuscript was handled by: Markus Hollmann, MD, PhD. Back to Top | Article Outline ACKNOWLEDGMENTS The authors thank Kari Johnson (Division of Gerontology and Geriatric Medicine, Department of Medicine, Harborview Medical Center, University of Washington, Seattle) and Yotam Bentov (Division of Gerontology and Geriatric Medicine, Department of Medicine, Harborview Medical Center, University of Washington, Seattle) for their assistance with the experiments.Back to Top | Article Outline REFERENCES 1. Bentov I, Reed MJ. Anesthesia, microcirculation, and wound repair in aging. Anesthesiology. 2014;120:760772. Cited Here... 2. Sgonc R, Gruber J. Age-related aspects of cutaneous wound healing: a mini-review. Gerontology. 2013;59:159164. Cited Here... 3. Brown-Borg HM. Hormonal regulation of longevity in mammals. Ageing Res Rev. 2007;6:2845. Cited Here... 4. Ashcroft GS, Horan MA, Ferguson MW. The effects of ageing on wound healing: immunolocalisation of growth factors and their receptors in a murine incisional model. J Anat. 1997;190 (pt 3):351365. Cited Here... 5. Carlson MA, Longaker MT. The fibroblast-populated collagen matrix as a model of wound healing: a review of the evidence. Wound Repair Regen. 2004;12:134147. Cited Here... 6. Wall IB, Moseley R, Baird DM, Kipling D, Giles P, Laffafian I, Price PE, Thomas DW, Stephens P. Fibroblast dysfunction is a key factor in the non-healing of chronic venous leg ulcers. J Invest Dermatol. 2008;128:25262540. Cited Here... 7. Sprenger CC, Plymate SR, Reed MJ. Aging-related alterations in the extracellular matrix modulate the microenvironment and influence tumor progression. Int J Cancer. 2010;127:27392748. Cited Here... 8. Bruce SA, Deamond SF. Longitudinal study of in vivo wound repair and in vitro cellular senescence of dermal fibroblasts. Exp Gerontol. 1991;26:1727. Cited Here... 9. Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012;49:3543. Cited Here... 10. Martin P. Wound healing—aiming for perfect skin regeneration. Science. 1997;276:7581. Cited Here... 11. Reed MJ, Penn PE, Li Y, et al. Enhanced cell proliferation and biosynthesis mediate improved wound repair in refed, caloric-restricted mice. Mech Ageing Dev. 1996;89:2143. Cited Here... 12. Rudman SM, Philpott MP, Thomas GA, Kealey T. The role of IGF-I in human skin and its appendages: morphogen as well as mitogen? J Invest Dermatol. 1997;109:770777. Cited Here... 13. Okubo Y, Siddle K, Firth H, et al. Cell proliferation activities on skin fibroblasts from a short child with absence of one copy of the type 1 insulin-like growth factor receptor (IGF1R) gene and a tall child with three copies of the IGF1R gene. J Clin Endocrinol Metab. 2003;88:59815988. Cited Here... 14. Bentov I, Damodarasamy M, Plymate S, Reed MJ. Decreased proliferative capacity of aged dermal fibroblasts in a three dimensional matrix is associated with reduced IGF1R expression and activation. Biogerontology. 2014;15:329337. Cited Here... 15. Santibañez JF, Quintanilla M, Bernabeu C. TGF-β/TGF-β receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2011;121:233251. Cited Here... 16. Liu SS, Richman JM, Thirlby RC, Wu CL. Efficacy of continuous wound catheters delivering local anesthetic for postoperative analgesia: a quantitative and qualitative systematic review of randomized controlled trials. J Am Coll Surg. 2006;203:914932. Cited Here... 17. Fassoulaki A, Sarantopoulos C, Melemeni A, Hogan Q. EMLA reduces acute and chronic pain after breast surgery for cancer. Reg Anesth Pain Med. 2000;25:350355. Cited Here... 18. Brower MC, Johnson ME. Adverse effects of local anesthetic infiltration on wound healing. Reg Anesth Pain Med. 2003;28:233240. Cited Here... 19. Radwan IA, Saito S, Goto F. The neurotoxicity of local anesthetics on growing neurons: a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine. Anesth Analg. 2002;94:319324. Cited Here... 20. Zink W, Graf BM. Local anesthetic myotoxicity. Reg Anesth Pain Med. 2004;29:333340. Cited Here... 21. Chvapil M, Hameroff SR, O'Dea K, Peacock EE Jr. Local anesthetics and wound healing. J Surg Res. 1979;27:367371. Cited Here... 22. Lucchinetti E, Awad AE, Rahman M, et al. Antiproliferative effects of local anesthetics on mesenchymal stem cells: potential implications for tumor spreading and wound healing. Anesthesiology. 2012;116:841856. Cited Here... 23. Reed MJ, Ferara NS, Vernon RB. Impaired migration, integrin function, and actin cytoskeletal organization in dermal fibroblasts from a subset of aged human donors. Mech Ageing Dev. 2001;122:12031220. Cited Here... 24. Fedder C, Beck-Schimmer B, Aguirre J, et al. In vitro exposure of human fibroblasts to local anaesthetics impairs cell growth. Clin Exp Immunol. 2010;162:280288. Cited Here... 25. Oliveira AC, Rodríguez IÁ, Garzón I, et al. An early and late cytotoxicity evaluation of lidocaine on human oral mucosa fibroblasts. Exp Biol Med (Maywood). 2014;239:7182. Cited Here... 26. Bernards CM, Kopacz DJ. Effect of epinephrine on lidocaine clearance in vivo: a microdialysis study in humans. Anesthesiology. 1999;91:962968. Cited Here... 27. Singh P, Roberts MS. Dermal and underlying tissue pharmacokinetics of lidocaine after topical application. J Pharm Sci. 1994;83:774782. Cited Here... 28. Reed MJ, Vernon RB, Abrass IB, Sage EH. TGF-beta 1 induces the expression of type I collagen and SPARC, and enhances contraction of collagen gels, by fibroblasts from young and aged donors. J Cell Physiol. 1994;158:169179. Cited Here... 29. Shi ZD, Ji XY, Berardi DE, Qazi H, Tarbell JM. Interstitial flow induces MMP-1 expression and vascular SMC migration in collagen I gels via an ERK1/2-dependent and c-Jun-mediated mechanism. Am J Physiol Heart Circ Physiol. 2010;298:H127H135. Cited Here... 30. Kenyon NJ, Ward RW, McGrew G, Last JA. TGF-beta1 causes airway fibrosis and increased collagen I and III mRNA in mice. Thorax. 2003;58:772777. Cited Here... 31. Reed MJ, Koike T, Puolakkainen P. Wound repair in aging. A review. Methods Mol Med. 2003;78:217237. Cited Here... 32. Gosain A, DiPietro LA. Aging and wound healing. World J Surg. 2004;28:321326. Cited Here... 33. Martino MM, Briquez PS, Güç E, et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science. 2014;343:885888. Cited Here... 34. Hanci V, Hakimoğlu S, Özaçmak H, et al. Comparison of the effects of bupivacaine, lidocaine, and tramadol infiltration on wound healing in rats. Rev Bras Anestesiol. 2012;62:799810. Cited Here... 35. Iwasaki K, Sudo H, Yamada K, Ito M, Iwasaki N. Cytotoxic effects of the radiocontrast agent iotrolan and anesthetic agents bupivacaine and lidocaine in three-dimensional cultures of human intervertebral disc nucleus pulposus cells: identification of the apoptotic pathways. PLoS One. 2014;9:e92442. Cited Here... 36. Park J, Sutradhar BC, Hong G, Choi SH, Kim G. Comparison of the cytotoxic effects of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes. Vet Anaesth Analg. 2011;38:127133. Cited Here... 37. Perez-Castro R, Patel S, Garavito-Aguilar ZV, et al. Cytotoxicity of local anesthetics in human neuronal cells. Anesth Analg. 2009;108:9971007. Cited Here... 38. Sztark F, Malgat M, Dabadie P, Mazat JP. Comparison of the effects of bupivacaine and ropivacaine on heart cell mitochondrial bioenergetics. Anesthesiology. 1998;88:13401349. Cited Here... 39. Lirk P, Haller I, Colvin HP, et al. In vitro, inhibition of mitogen-activated protein kinase pathways protects against bupivacaine- and ropivacaine-induced neurotoxicity. Anesth Analg. 2008;106:14561464. Cited Here... 40. Lirk P, Haller I, Myers RR, et al. Mitigation of direct neurotoxic effects of lidocaine and amitriptyline by inhibition of p38 mitogen-activated protein kinase in vitro and in vivo. Anesthesiology. 2006;104:12661273. Cited Here... 41. Junnila RK, List EO, Berryman DE, Murrey JW, Kopchick JJ. The GH/IGF-1 axis in ageing and longevity. Nat Rev Endocrinol. 2013;9:366376. Cited Here... 42. Klempt M, Klempt ND, Gluckman PD. Hypoxia and hypoxia/ischemia affect the expression of insulin-like growth factor binding protein 2 in the developing rat brain. Brain Res Mol Brain Res. 1993;17:347350. Cited Here... 43. Nordqvist AC, Holmin S, Nilsson M, Mathiesen T, Schalling M. MK-801 inhibits the cortical increase in IGF-1, IGFBP-2 and IGFBP-4 expression following trauma. Neuroreport. 1997;8:455460. Cited Here... 44. Walter HJ, Berry M, Hill DJ, Logan A. Spatial and temporal changes in the insulin-like growth factor (IGF) axis indicate autocrine/paracrine actions of IGF-I within wounds of the rat brain. Endocrinology. 1997;138:30243034. Cited Here... 45. Lewis DA, Travers JB, Somani AK, Spandau DF. The IGF-1/IGF-1R signaling axis in the skin: a new role for the dermis in aging-associated skin cancer. Oncogene. 2010;29:14751485. Cited Here... 46. Mueller RV, Hunt TK, Tokunaga A, Spencer EM. The effect of insulinlike growth factor I on wound healing variables and macrophages in rats. Arch Surg. 1994;129:262265. Cited Here... 47. Reiser K, McGee C, Rucker R, McDonald R. Effects of aging and caloric restriction on extracellular matrix biosynthesis in a model of injury repair in rats. J Gerontol A Biol Sci Med Sci. 1995;50A:B40B47. Cited Here... 48. Radwan IA, Saito S, Goto F. The neurotoxicity of local anesthetics on growing neurons: a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine. Anesth Analg. 2002;94:319324. Cited Here... 49. Shi Y, Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113:685700. Cited Here... 50. Waite A, Gilliver SC, Masterson GR, Hardman MJ, Ashcroft GS. Clinically relevant doses of lidocaine and bupivacaine do not impair cutaneous wound healing in mice. Br J Anaesth. 2010;104:768773. Cited Here... 51. Cristofalo VJ, Allen RG, Pignolo RJ, Martin BG, Beck JC. Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation. Proc Natl Acad Sci U S A. 1998;95:1061410619. Cited Here... 52. Caracas HC, Maciel JV, Martins PM, de Souza MM, Maia LC. The use of lidocaine as an anti-inflammatory substance: a systematic review. J Dent. 2009;37:9397. Cited Here... 53. Jejurikar SS, Welling TH, Zelenock JA, et al. Induction of angiogenesis by lidocaine and basic fibroblast growth factor: a model for in vivo retroviral-mediated gene therapy. J Surg Res. 1997;67:137146. Cited Here... 54. Bentov I, Reed MJ. The effect of aging on the cutaneous microvasculature. Microvasc Res. 2015;100:2531. Cited Here... 55. Bamigboye AA, Hofmeyr GJ. Local anaesthetic wound infiltration and abdominal nerves block during caesarean section for postoperative pain relief. Cochrane Database Syst Rev. 2009:CD006954. Cited Here... 56. Zaric D, Pace NL. Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics. Cochrane Database Syst Rev. 2009:CD003006. Cited Here... Copyright © 2016 International Anesthesia Research Society


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Click on the image for licensing terms
Towards the end of our week's holiday in Croatia we met up with our daughter Allie for the day, and decided to take one of the many boat excursions around the islands just off the Adriatic coast.
I'm certainly glad we did, otherwise we would never have got to see some lovely places, such as Maslinica on the small island of Solta, pictured here.
An absolutely charming seaside village, with some lovely photogenic views to enjoy.
This image features a lovely wooden hulled small boat tied up to the side of the promenade, floating on the clear green waters of the Adriatic.
Filename - croatia maslinica harbour 04
Lens - 24-105mm zoom @ 24mm
Exposure - 1/80 sec @ f8, ISO100
Filters - Polarising filter used to reduce glare and enhance colours.
Location - Maslinica, Croatia
Image enhancements - Adobe Lightroom
Comments - Image under exposed slightly to preserve bright highlights.
All content copyright © Howard Litherland 2009-2019 unless otherwise stated.

subset: commoncrawl


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Missions Incubator Application
We want to start off simple. Take a moment to fill out the following application. The Incubator Board of Approval will contact you to setup a interview once your application and letters of reference have been received. Once you submit your application please send three (3) letters of reference in English or Spanish to firstname.lastname@example.com no later than 5 business days following your application submission.
Requirements for Applicants:
-Has not served in any capacity previously at Refugio Solté (internship/staff)
-Must be above the age of 21
-Able to fulfill weekly and monthly responsibilities pertaining to the Mission Incubator
-Complete an interview either in person or via Phone/Video with the Incubator Board of Approval


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The family of Erik Roner, all of us at Nitro Circus, and the burgeoning Live Like Roner Foundation are honored to welcome everyone to A Night to Live Like Roner, a charity event full of fun and memories, Aug. 2 at SeaLegs at the Beach on Bolsa Chica State Beach in Huntington Beach, California. The event is free and open to the public starting at noon. At 5pm ticket holders will be welcomed inside for an exclusive gathering to honor the life and legacy of Erik Roner. Get your tickets here while they last.
The event will benefit Roner's wife, Annika, and his two kids, Oskar and Kasper. A portion of the proceeds will also go to the Live Like Roner Foundation, which will assist other families of action sports athletes in their greatest time of need. A day at Pastranaland with Travis Pastrana is up for auction, and there are a ton of other one-of-a-kind items and experiences available. Head to LiveLikeRoner.com for a sneak peek and to start bidding now in the online auction.
This event is going to be so much fun for the whole family. The list of entertainment is long, but it includes a skydive demonstration, carnival games, great food and beverages, live music, silent and live auctions, and a snow rail jam on actual snow.
On Aug. 1, the day before, the Hurley store in Pacific City is hosting a pre-party from 5pm-9pm. If you buy any Hurley shirt you can have a Live Like Roner logo screen printed on it, and all proceeds will go to the Athlete Recovery Fund, whose mission statement is:
To provide professional athletes in action sports with financial support after a severe injury and granting funds for rehabilitation, equipment, long-term disability and educational scholarships.
Head over to LiveLikeRoner.com right now for more info, and we'll see you next week!


text: << Thursday 17 June, 2004This page was originally published on Friday 18 June, 2004.Browse our archives: 12345678910111213141516171819202122232425262728293031JanuaryFebruaryMarchAprilMayJuneJulyAugustSeptemberOctoberNovemberDecember20032004200520062007200820092010201120122013201420152016201720182019Saturday 19 June, 2004 >>Click here to read today's edition! >> NASA Today Search the World News Network Any Language Afrikaans Czech Danish Dutch English Finnish French German Hausa Hungarian Indonesian Italian Malay Norwegian Polish Portuguese Romanian Slovak Spanish Swahili Swedish Tagalog Turkish Advanced Search Technology Science Space Eclipse Solar News WN Science Archive Feedback Site Map WN RELATED Asia Business Science correspondent Solar News Space Centre World Finance World Global Headlines News Archive Weather Photos Slideshow REGIONAL WN Africa WN Asia WN Australasia WN Caribbean WN Europe WN Mideast WN C. America WN N. America WN Pacific WN S. 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Smoke and Mirrors
'The monuments are supposed to commemorate kings and religions, heroes, dogmas, but in the end, the man they commemorate is the builder.'
J. Bronowski, The Ascent of Man, 1974
Religious buildings are designed to lead us in, amplify our sense of experience and heighten belief. Giles Alexander's paintings operate on the same principal as the structures they depict, drawing us in and urging us to go deeper into the architecture.
The intricate detail in these glorious buildings tempts us to comprehend their execution. So too is our experience with Alexander's exquisite paintings, which call us to follow the path to its end, to worship the humanist pursuits embodied in both the building and the painting.
Journeying through fine layers of paint the viewer notices a deep, mirror-like resin veils the image. A paradox of space and surface arises through awareness both of infinite depth and the presence of one's own reflection.
These are carefully considered and meticulously constructed images, and their faultless execution pays homage to the master masons and artisans of religious antiquity. Ultimately the work questions exactly what it is we are worshiping.
Guy Maestri 2009


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Dion Horstmans. Acrylic on Steel. 120cm x 240cm.
Dion Horstmans is a dynamic sculptor who works in steel, a prolific exhibitor and commercial success. Born in New Zealand and now based in Sydney, he's been a regular exhibitor at Sculpture by the Sea since 2011. In the same year, he was invited to show his work at The Art of War exhibition at Sydney's Casual Powerhouse. Indeed, Horstmans' work in steel has a war-like energy to it. Perhaps not dissimilar to its creator, the work is often imposing; definite in structure; and engages with enigmatic purpose.
For some time, I had been searching for a concept where my painting could inextricably link the medium to the subject. When Dion approached my radar, the imagination began sparking. 'We met up, and he was instantly interesting to me as a subject. I loved the idea of painting his portrait on his own medium. Plus, his huge personality and impressive physicality were something I was really excited about representing on a big scale'.
I invited Dion to build the canvas, welding the frames on the steel we received from his usual supplier - in turn further adding his DNA deeper into the piece.
Painting on a steel canvas that measures 240cm tall, was a deliberate choice - I wanted the piece to represent Dion in as many ways as I could. I wanted the composition to be imposing. And I wasn't about to compromise on size with Dion as a subject.


text: Patagonia is massive and diverse, so we've compiled a list of some of the best trail runs in Patagonia. Between the glaciers, grasslands, rolling hills, impressive high peaks, rivers, and lakes, there's plenty to explore. Check out our list of our favorite trail runs in Northern Patagonia, Southern Patagonia, and the best new trail run in Patagonia.Read More


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Tommyknocker Almond Creme/
You know I'm a sucker for fun label art, right? Well Tommyknocker Almond Creme has tickled my fancy with their dwarfish looking miner holding a foaming mug. He looks so happy, almost Santa like in his serenity. While his face doesn't show the markings of working underground you can tell he's pleased with his drink choice.
Ingredient wise Tommyknocker Almond Creme is all natural with Carbonated Water, Pure Cane Sugar, Almond Concentrate, Aged Organic Vanilla Extract & Citric Acid. That's a pretty good list of ingredients if you ask me… and you did since you're here.
HA! The bottle cap even has a happy looking dwarf on it. Time to remove him from the equation and start this review.
Wow… that smells like almond… and cream. That's pretty dang impressive. I cannot wait to try this.
They did a really good job making this, I can tell they put in a lot of care. I just… I just don't really like the flavor. It tastes like liquid almonds with a sweet cream behind it. Even the "dryness" of
the almond is present. I don't mean that the soda tastes dry, it's just the sensation that can only be duplicated by placing some almonds in your mouth. It's incredibly authentic in taste and mouthfeel.
Dryness aside, it's a fairly refreshing beverage in terms of feel. Tommyknocker Almond Creme is incredibly smooth, almost buttery in nature. Even though it's a creme it doesn't really stick to your teeth or have any kind of syrupy nonsense..
As you may have figured out by the former sentence carbonation wise it's a very tame soda. No real fizz to be found here, though I'm not sure that would change my opinion. The finish is very similar to the start in terms of flavor and lingers for a while after each sip.
I want to like this so very badly, I really do. Sigh. The flavor just isn't me. I am however looking forward to more Tommyknockers sodas though.
Verdict - Buyer Beware
This was purchased at Rocket Fizz Houston


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Plaid Hat Band
Plaid Hat Band
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Instantly change up your look with a new hat band! Bands also can be worn in your hair, tied onto your favorite bag, or around your neck as a neck tie!
The Plaid Hat Band is shown here on the Emma and Scottie Black.
Check out our other Accessories.


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The purpose of this post is to demonstrate how easy it is to provide an agenda that is easy to read and easy to locate your particular item of interest. I have taken the PDF agenda available from the District of Saanich website and broken it down into component sections. Continue reading Saanich Meeting Agenda October 5, 2015
Tag: District of Saanich
Feb 12 Council Summary & Observations
In my years observing what goes on at Victoria City hall, I've always tended to focus more on committee (e.g., Governance and Priorities, and Land Use and Planning as the main two) than Council meetings. I do this because a) in my experience Council is hard to follow and b) committee meetings are where the most substantive conversation occurs and decisions are made and later ratified at subsequent Council meetings. Continue reading Feb 12 Council Summary & Observations


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Hello, and welcome to the Gamma Phi chapter of Alpha Gam at Georgia Tech. Feel free to explore, and see what we're enthusiastic about! We hope you get a glimpse of what we pride ourselves on: genuine friendships, giving back, scholarship, and of course the values and purpose of Alpha Gamma Delta.
Here at Alpha Gam, our sisterhood drives everything we do. As an out of state student, my sisters quickly became my support system while being far away from home. Everything from hardships and bumps in the road, to life chats and celebrations; my sisters are there for me whenever I need them most.
As you walk around our website, we hope you can see how close our sisterhood is. If you have any questions, please reach out, we would love to hear from you! Thank you for stopping by!
Kimberly Fulton


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Space.com (January 18, 2010)
"The first wealthy tourists rocketing into space from Florida may start their trips in Jacksonville, not the Space Coast.
"The Federal Aviation Authority last week approved Cecil Field, a former naval air station about 25 miles southwest of the city's downtown, as a spaceport for commercial launches of spacecraft like Virgin Galactic's SpaceShipTwo.
" 'We're extremely excited and very much looking to the future to work with potential operators,' said Todd Lindner of the Jacksonville Aviation Authority...."
"...Cecil Field's license makes it the nation's seventh commercial spaceport. It permits 'horizontal' launches of vehicles that would take off and land like planes at the site's 12,500-foot runway...."
"...'Initially, the operations will be for your upper-end leisure traveler, the person who wants an exciting ride, Lindner said.
"Later, the market could expand to microgravity research flights and launches of small satellites into orbit from motherships...."
What? No Martian Princesses?That's the control tower of Cecil Field, in the photo.
Doesn't look much like part of a spaceport, does it? No useless 'streamlining' or lightning-bolt logo; no green-skinned visitors, who look quite Anglo-American, apart from their complexion and silver lame' jumpsuits; no rocket ships that look like a WWII V2 with wings.
That's because this one is real, and those were imaginary: often, I suspect, made in a hurry, on a low budget.
Judging from artists' renderings the passenger terminal at Spaceport America, in the southwest, will have the ultra-contemporary streamlined look of science fiction spaceports. Even there, though, many of the structures now in use don't look all that much like something out of Buck Rogers of Star Trek.
As the Cecil Field spaceport grows, some of the new structures will probably look like something out of the 21st century. Which figures, since that'll be when they get designed and built.
Another Step Toward the Stars: Living the DreamYou may have lived your entire life in a world where bandwidth was important when choosing an ISP; when robot spaceships were exploring the outer Solar system; and the Space Shuttle was an aging, almost antique, vehicle.
I was born during the Truman administration. I remember my parents' first television set. And how amazing color television was, years later. I learned to program computers when and perforated paper tape were standard information storage technologies.
And, I remember Sputnik, the Mercury program, and the landing at Tranquility Base.
I'm not particularly sorry that the (wildly optimistic) Lunar settlements of "2001: A Space Odyssey" aren't there. Well, maybe a little.
The point is, I've seen space travel grow from a pipe dream to a tourist industry. For me, it's like living in a boyhood dream come true.
I've been 'living in the future' for quite a while now. It's not the wildly optimistic techno-kitsch festival of pre-sixties speculation: and it sure isn't the still-fashionable 'and we're all gonna die' horror of post-sixties prognosticators. (More, at "- - - 'And We're All Gonna Die!'," Drifting at the Edge of Time and Space (June 30, 2009))
Space Tourism?! Oh, the Crass Commercialism!And, no: I don't mind that people who have the money are paying to go into space. Any more than I mind advertising on launch vehicles. (It's been done: quite a few years ago. And at least one terribly earnest scientist had a fit.)
They're providing capital and incentive to improve and develop technologies that will be more efficient than what we've got now.
Delta Flights to Orbital Hotels? Spaceliners?Think about the automobile. It started out as a sort of toy for the rich. During the 20th century, automobiles became a major part of American (at least), and an important part of transportation systems around the world.
I think we're looking at launch vehicles going through a similar process. We're not at the 'spaceship in every garage' stage - and probably never will be. Or won't be for a very long time.
On the other hand, not too long ago I posted about Bigelow Aerospace's plans for marketing space habitats to international space agencies and multinational corporations.
Make the things a little bigger, add some amenities and a customer-service-minded staff, and I think we're looking at luxury resorts.
Given time, I don't see why there wouldn't be a sizable number of people working - at least - in low Earth orbit, with commercial shuttle flights serving their transportation needs.
Spaceliners? As a sort of cruise ship, maybe - but that'd be more the sort of situation we have with orbital luxury hotels. I suspect it'll be generations before enough people live on the Moon or (more likely, I think) Mars to support commercial passenger travel between planets.
Come to think of it, there's an intriguing possibility about living in the clouds of Venus. But that's another topic.
Related posts:
- "Second Smallest Exoplanet Found: HD 156668b (Caution! Geeky Content!)"
(January 10, 2010)
- "Crew-Optional Dragon Cargo Ship Ready for Testing Soon"
(December 16, 2009)
- "Hypersonic Vehicles: Waveriders to Space"
(November 2, 2009)
- "ISS Space Station Walkthrough, Looking Ahead"
(October 28, 2009)
- "New Rocket Fuel: Aluminum and - - - Water?!"
(October 21, 2009)
- "When it's Time to Build Spaceships, People Will Build Spaceships"
(October 4, 2009)
- "A Freighter Unloads its Cargo: What's the Big Deal?"
(September 20, 2009)
- " 'The future ain't what it used to be.' Probably Just as Well"
(August 30, 2009)
- "Alan Stern and Space Tourism"
(July 18, 2009)
- "Tranquility Base as an Archaeological Site"
(July 16, 2009)
- "Spaceport Hawaii: Maybe"
(July 11, 2009)
- "Groundbreaking at Spaceport America: World's First Purpose-Built Commercial Spaceport"
(June 20, 2009)
- "Warp Drive Might Not Be Stable: Physcisists Take Another look at Alcubierre's Work"
(June 12, 2009)
- "Warp Drive: Yes, it May Be Possible; But Don't Hold Your Breath"
(May 7, 2009)
- "Spaceport America: Still Open for Business"
(November 6, 2008)
- "Spaceport Development Tax on Otero County Ballot"
(November 5, 2008)
- "Spaceport America: It's Real, and Open for Business"
(October 26, 2008)
- "Spaceports: the Blog"
(October 26, 2008)
- "Dubai Architecture: A Photo Gallery"
(October 25, 2008)
- Dubai's spaceport
- It won't be the world's first
- But It'll probably be among the most spectacular
- Dubai's spaceport
- "Cloud Cities of Venus"
(July 25, 2008)
- "Bigelow Aerospace Space Habitat Prototype Passes Milestone"
(May 12, 2008)
- "Coming Soon to a Spaceport Near You"
(March 26, 2008)


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JRF Alumni: Where Are They Now? Patrick Graham
June 14, 2015 - Alumni
The Jackie Robinson Foundation (JRF) can now add "Super Bowl" champion to its list of alumni achievements. JRF Scholar alumnus Patrick Graham, a Linebackers coach for the New England Patriots, earned a Sociology degree from Yale University in 2001.
"To be recognized by an organization like the Jackie Robinson Foundation is a great honor," said Graham. "To be associated with a great family, the connections I made, and the different people I met, these are lifelong bonds."
Starting his coaching career at the collegiate level with a stop at the University of Notre Dame, Graham joined the Patriots as a coaching assistant in 2009. In his first three seasons as a defensive positional coach, the Foxboro, MA native helped the Patriots lead the NFL in turnover differential in 2010 and 2012. The team also finished first in the AFC in 2011. With more than 111 million people watching the Big Game, the Patriots' defense helped seal the team's place in history as the winners of Super Bowl XLVI.
Considering he is part of one of the most celebrated sporting events across the globe, Patrick thinks of the opportunities he has in connection to Jackie's sacrifices.
"Being involved in athletics makes me think of Jackie's legacy," he said. "Here I am, now as a 36-year-old man coaching, I definitely think about the history behind it. The program is a great opportunity for students looking for help with tuition but the chance to meet people is the most important part."


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Saturday, April 25, 2009
Fresh from the Garden
We have begun to harvest some of our own signature blooms here at Flowerwild. There is something so rewarding about watching a garden grow. Some of the plants that are flowering with profusion right now are the rambling roses and the clematis vines; which I should add, the nursery tried to dissuade me from growing....not the right climate they said! Too hot and dry. They seem to be preforming terrifically. Can't wait to add more. Passion vines are also blossoming. They have a little "eyelash" center wich makes them look very sea creature-y. Like 'em!!!
Here are some simple arrangements of flowers you can cut from your own spring garden...
The Lilac I bought at the local farmer's market. Super lush!!
Use HOT HOT water off the tap to invigorate droopy flowers.
Labels: clematis, garden roses, trumpet vine
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Austin is strategically located in Central Texas, and as the capitol city, is home to many of the state's government offices. The BearCom Austin two-way radio dealer serves many of these state and local agencies, as well as public service organizations and companies doing business with the state.
Austin is also home to the University of Texas and many other enterprises that BearCom serves including: healthcare, construction, technology companies, manufacturing, distribution centers, the hospitality industry and K-12 schools. Throughout Travis and nearby counties, the BearCom Austin team, working from our Round Rock location, serves customers in all segments with two-way radio (walkie-talkie) and other advanced wireless voice, data and push-to-talk solutions. BearCom Austin provides two-way radios to organizations of every kind to increase their efficiency in safety, security and productivity
When you choose BearCom in the Austin region, you're partnering with a two-way radio dealer who can meet your unique specifications and provide the wireless communications solutions you need to be successful. In addition to two-way radio systems, BearCom in Austin offers push-to-talk networks, voice communications consoles, in-vehicle wireless equipment installation and tracking, RFID technologies, and Uninterrupted Power Supplies (UPSs), as well as deep levels of expertise designing and deploying FirstNet broadband communications networks for first responders.
Two-Way Radio Dealer in Austin: Rentals
As an end-to-end two-way radio dealer in the Austin area, we make rental events more successful by providing the right equipment for any sized event to improve communications, enhance service levels and increase safety. Our Austin team specializes in rental solutions of every scope – from large government events, to regional music festivals and eclectic outdoor activities to more moderate occasions such as meetings, conventions and graduations. With more than 30,000 rental units in our fleet, BearCom provides both short-term and long-term rental options for special events, sporting events, meetings and more.
BearCom Austin Two-Way Radio (Walkie-Talkie) Dealer and Integrator
BearCom is a Motorola Solutions Radio Solutions Channel Partner, as well as a Service Elite Specialist. We have deep levels of experience and domain expertise to offer the best wireless system technologies and end-to-end solutions, no matter how simple or complex the environment.
Our two-way radios include name brands from Motorola Solutions, Kenwood, Icom America and more. The equipment we offer includes two-way radio portables, mobiles, repeaters, batteries, accessories, call boxes, Bi-Directional Amplifiers (BDAs) and antenna systems, as well as infrastructure solutions to build out wireless voice and data communications, MOTOTRBO systems, mesh networks, video surveillance, and more. We are well-versed in complex security considerations, and have equipment and accessories for any need.
With branches across the country, including here in Austin, along with unmatched national resources, you can count on BearCom to provide everything you need.
For a free evaluation of your two-way radio communications needs, contact us today at (512) 279-5950.
As a Motorola Solutions Service Elite Specialist with Certified Service Center status, BearCom offers our customers unsurpassed wireless solutions expertise in repair, design, and deployment. Our Technical Services Group holds advanced engineering degrees, as well as comprehensive credentials for R56 site installation, DMR and P25 networking, and many other wireless industry certifications for voice and data integration.
About BearCom
BearCom provides a broad line of high-performance wireless communications products, services and complete mobility solutions. Founded in 1981, BearCom is America's only nationwide dealer and integrator of wireless communications equipment and solutions, serves customers from 40 branch offices located throughout the U.S. and employs approximately 500 people. BearCom is Motorola Solutions largest two-way radio dealer in the world and has earned Motorola's prestigious Service Elite Specialist designation.
Austin BearCom Two-Way Radio Dealer: Location Map


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16 family friendly destinations to explore with your family in Switzerland, all come highly recommended by Swiss-based Families.Read More
Family Friendly Winter in Switzerland: Each week during the winter a local family will share their favourite place to spend their winter days. You'll discover the best way to get there, which skiing abilities the area caters to, where to rent skis, and which restaurants to try. First up it is Elm with Tanya from Moms Tots Zürich.
Read More


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Level 2 Ayurveda for yoga teachers with Keren & Lucy, Oct 2020
Ayurveda for yoga teachers, 50 hours, 29th October -1st November 2020
Ayurveda is an ancient science that literally means the knowledge of life. The beauty of Ayurveda is at its very core it gifts us with the ability to care for ourselves and ultimately heal ourselves. It is a science that works for every individual as it sees you as just that, an individual that is wholly unique and therefore any health issues are wholly unique to you. Many of todays healing modality came out of Ayurveda – herbalism, aromatherapy, massage therapy, nutrition, yoga as therapy, meditation, pranayama and so much more. It's an in-depth and complex science but with some smart and grounded knowledge, it's easy to incorporate Ayurveda into your life and home for a happier healthier you.
In this 50hr training, you will be introduced to the Ayurvedic principals of maintaining balance, understanding the dosas and how to recognise an imbalance, we will then look at how we can use this understanding to guide your approach to yoga, nutrition and diet, meditation and pranayama, cleansing practices and lifestyle choices.
You can expect our days together to be broken up into in-depth theory to give you a basic but grounded understanding of Ayurveda and the three doshas and the main principles of Ayurveda and then delving into how a physical practice can support balance inline with an Ayurvedic approach.
- Yoga asana by Dosha
- Meditation and pranayama practices to bring balance
- Dosha Assessment and recognising imbalance
- Dinacharya (Daily Routines)and Ritucharya (Seasonal Routines)
- Ayurvedic Diet for Dosha balance
- Common aliments and your Ayurvedic home pharmacy
Keren has been studying Ayurveda and incorporating it into her life for over 7 years. In 2017 Keren travelled to New York to study Ayurveda for women's health with Dr Ali Cramer and Dr Claudia Welch which inspired her to then take the huge step to study as an Ayurvedic practitioner with Dr Deepika at the Ayurvedic Institute in Croydon. This 750 hour course equipped Keren with a deeper understanding of how we can incorporate Ayurveda into our lives for happiness and health and while she firmly believes (in fact knows!) she will continue to study Ayurveda for the rest of her life, she is excited to share some of what she has learnt in this short course
Lucy was first exposed to Ayurveda and its potent wisdom whilst living in India 12 years ago. From then it has had a profound effect on how she lives her life and the lifestyle choices she has made. She was lucky enough to study with Rose Baudin as part of her level 2 training 7 years ago and was introduced to deeper Ayurvedic wisdom and how we can use this knowledge to inform our yoga practice. It was Lucy's connection with Rose that led her to meeting and having the chance to study with Dr. Robert Svoboda, one of the world's leading voices on Ayurveda. The balance and ease that this living body of wisdom has bought into Lucy's life is something she will forever be grateful for and is excited to share this passion.
COST: £395 OR £350 early bird payable by 1st April 2019. £75 deposit payable on booking and installment plan available if booking ahead of the course. Spaces limited to 15.


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Kern County
The American Red Cross has been serving Kern County communities since 1917, bringing hope and comfort to families every day. Red Cross volunteers turn compassion into action through a diverse array of programs and services. Whether it's a single house fire or global conflict, we respond with food, shelter, and hope. Last year 56,963 families in Kern County were assisted by local Red Cross volunteers delivering core mission services to youth, adults, senior citizens, local businesses, and organizations.


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Question: My question is simple; I love cats and dogs, but have never had one of my own. Should I get a pet?!
Dear Reader,
Ha, if only the answer were that simple.
Pets offer an incredible joy that everyone should experience in their life. Whether it's to provide you with company and a new BFF, a family pet, a service animal, as practice for or in lieu of children, or whatever other reason, pets are fantastic!


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Graduation Work 2016
Paradise Patterns
For my Graduation Show I had the chance to use a classical room to show my work. Because of this room, I was not able to hang up anything, and that is why I accepted the challenge to exhibit my work.
I found a resolution to make one big painting in the middle of the room. The big painting became something of a Decor.
A constructed and theatrical scene where different birds and curtains formed a weird play together.


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Intercoder reliability is usually estimated with a summary index, and yet the limitations concerning the indexing approach have been well noted. This study critically reviewed all the existing major modeling approaches to estimating intercoder reliability, and empirically tested and further compared these approaches. It was found that latent variable modeling, also called the second-generation SEM, generally perform better than log-linear modeling, and is able to explain the paradox haunting some indices, and to spot the sources of disagreement among coders. Implications were discussed at last.
Quality & Quantity – Springer Journals
Published: May 20, 2014
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Yesterday I talked about resistance. Today I'm focused on going with the flow. It reminds me of when I went white water rafting with my family. How the river pulled us along its current. I remember thinking how hard it would be to try to paddle against it. It would be an endless struggle going against its resistance. As we floated along there were lots of obstacles in the way that we had to work our way around. If we lost our focus it would have been easy to get stuck. That's when panic and fear can set in causing us to easily become disoriented. Thank goodness we had helpers floating around us who could get us unstuck.
Real life is this way. We can be floating along going with the current of life. Than suddenly we get stuck by the obstacles that get in our way. Confusion sets in. We find ourselves resisting the direction we need to go. Fear comes into play, followed by disillusionment and we become disoriented. There is no one to help us get unstuck. Even with God's help we can't become unstuck until we are willing to let go of that which stands in our way.
As I prepare for Thanksgiving day instead of focusing on all the work there is to do, and what comes after this holiday. Remembering the people I love and how thankful I am to have them in my life reminds me what Thanksgiving is all about in the first place. Being in the flow of all I have to be grateful for keeps me centered and focused on the direction I'm going.
Wow! It's a whole lot easier to float along the current of love. I'm also finding it to be a lot more fun!


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Approaches: Integrative, CBT, Gestalt Therapy, Systemic Therapy, Gottman Couple Therapy as well as Coaching and Motivational Dialogue
Anna Nauka holds a Master's Degree in Psychology at the University of Wroclaw. She is a member of Psychological Society of Ireland. She attends regular supervision and abides by the code of ethics of the PSI.
She has completed a first level coaching training from the Center of Education CEL in Wroclaw. And certified in Couples Counselling in PCI College and Family Therapy in The Institute of Integrative Counselling and Psychotherapy. She has also completed Levels 1, 2 and 3 in Gottman Couple Therapy.
Anna is committed to continuous personal development and has completed further training in Bereavement & Loss, Working with Trauma, Childhood Sexual Abuse, Somatic Experiencing and Mindfulness.
Anna has practiced in the Counselling Center at the University of Wroclaw and also in the Lower Silesian Psychotherapy Center. Since 2013 she has been working with MyMind, where she provides individual sessions for adults and children as well as Couple and Family Therapy. She has conducted workshops and trainings in the areas of motivation, communication, body image and assertiveness. Anna practices as Integrative Counsellor and Psychotherapist using elements of CBT, Gestalt Therapy and Systemic Therapy tailoring the therapy process to suit each client's individual needs. She believes that every person has a unique strengths and resources that allow them to make even the most difficult changes in their lives.
Anna Nauka works with clients experiencing:
- Depression
- Anxiety
- Stress
- Lack of motivation
- Loss and Bereavement
- Trauma
- Low confidence or self-esteem
- Relationships difficulties
- Communication problems
- Relationship and Family conflict
- Parenting
- Teenage issues
- Bullying


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RoadsideAmerica.com Team Field Report
- Directions:
- Climax Gentleman's Club. On the north side of US 22, five miles east of Hwy 66 or four miles west of Hwy 981.
- Hours:
- Closed summer 2009 after owner's death.
- Status:
- Closed
Results 1 to 2 of 2...
World's Only Drive-Thru Strip Club
Not for the average family, but convenient for men who can't be bothered to get out of their cars. Roadsideamerica.com Report...
Visitor Tips and News About World's Only Drive-Thru Strip Club
Reports and tips from RoadsideAmerica.com visitors and Roadside America mobile tipsters. Some tips may not be verified. Submit your own tip.
The Climax Drive-Thru Strip Club recently closed.[Paul, 01/19/2010]
A setback for the Drive-Thru Tour. Nick Climax (Fratangelo) died last January 15 -- he was only 58 -- and although the club tried to make a go without him, it closed over the summer of 2009.
Latest Tips Across Roadside America
Catch up on the latest discoveries from the road.
Explore Thousands of Oddball Tourist Attractions!
Unique destinations in the U.S. and Canada are our special obsession. Use our attraction recommendation and maps to plan your next road trip.


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Returns Guarantee
There's just something about painting flowers in any setting – alone or in bright clusters throughout a field. Before you start your creative process, this mug gets you going, both with its 17 oz. for your favorite energizing hot beverage and a watercolor graphic against a solid background.


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Marriage & Family Therapist
(408) 508-6248
M.A. Marriage & Family Therapist, Western Seminary
B.S. Psychology, Santa Clara University
California Association of Marriage and Family Therapists (CAMFT)
Drug and Alcohol Addictions Studies Certification (in process)
Certified Addiction Specialist, emphasis in Sexual Addiction (in process)
Prepare/Enrich Certification
Women's Issues
Partners of Sex Addiction
Cultural Issues
Grief Loss Issues
Family of Origin Issues
Custody/Divorce Recovery for Family
Marriage Counseling
Premarital Counseling
Spiritual issues
Seeking help and taking the first steps toward recovery, healing, and self-growth takes courage and strength. It is a privilege to journey with you. I offer compassion, empathy, and guidance to promote your healing, growth, and restoration from painful life experiences such as addictions, traumas, betrayal, anxieties, and relationship difficulties.
I specialize in working with partners who have been affected by individuals who struggle with sex addiction, as well as women who struggle with confusion and shame caused by sexual compulsivity.
I also have a heart and passion for helping couples break through relationship patterns that aren't working by doing practical and deep work that promotes change. The goal is to create relationships that will not only work, but are also meaningful, intentional, and enjoyable!
As a therapist, I use a variety of research based therapeutic tools that best fit the needs of each client. I am an EMDR (Eye Movement Desensitization and Reprocessing) trained therapist and have certifications in Addictions Counseling and Prepare/Enrich Pre-Marriage and Marriage Counseling. There is healing, recovery and hope in store for you!
Muna understands the different dynamics that come with couples counseling. She creates an environment that is safe and allows room for hard conversations and desired healing for couples. Muna's work moves beyond the counseling room. As she leaves couples with tasks and assignments to try on their own to reach the maximum effect possible from the resources put into attending couples counseling.
Partners of Sex Addicts
Muna works with partners of sex addicts to help them find comfort and healing from the crisis that they are facing. The partner's experience is traumatizing and leaves the partner confused, anxious, and emotionally distressed. Muna creates an environment for the partner to heal from the relational trauma, and experience personal growth and rebuild trust with their partner (the sex addict).
Young Adults
Young adults are faced with many transitions and new awareness to themselves, family, work, and relationships, which can cause distress and discomfort. Muna guides and helps her clients to reach their desired goals.
Muna also enjoys working with young adult couples in pre-engagement, pre-marital, or marital therapy. Muna's goal for each couple is to develop healthy communication, boundaries, and trust, which creates spiritual, emotional, and physical health in relationships.
Addiction Recovery
There is hope for full recovery from your addiction! Muna works along side her clients to help them find and maintain recovery.
Treatment is based upon research that is proven to maintain sobriety: individual counseling including trauma recovery therapy, along with support groups (like 12-step meetings).
Sexual addiction and its compulsions create overwhelming shame, especially for women struggling with the addiction. Muna cares about your recovery and her desire is to help you reach your full potential, while redeeming your sexuality and finding freedom from the shame and the addiction.


text: Redlady 0 Report post Posted March 9, 2015 This might be a dumb question, but when I see video's of warlocks doing CM's, they usually seem to be destro. I had always thought demo with Cata, Darksoul talent and grim:service would be the better choice now cause of the chaos wave/HoG, felguard spin and extra felguard spin on the adds. Add packs don't seem to be big enough to keep fire&brimstone going since the RoF nerf. But I have barely touched destro since WoD (never liked the spec much) and I might be missing something. Can anyone tell me why destro would be a better choice for CM's or whether demo might still compete cause of the burst aoe dmg? Quote Share this post Link to post Share on other sites


text: Contents Performance Analytics and Reporting Previous Topic Next Topic Analyze Spotlight data Subscribe Log in to subscribe to topics and get notified when content changes. ... SAVE AS PDF Selected Topic Topic & Subtopics All Topics in Contents Share Analyze Spotlight data Combine Spotlight data with data from the source table to perform detailed analysis on high-priority work. When the total weight of a record included in a Spotlight group exceeds the threshold for that group, a new record is created on the Spotlight [spotlight] table. This table stores the record sys_id in the ID field, as well as the total weight for that record in the Score field. To perform detailed analysis and to easily view record details along with the Spotlight weight, create a database view between the Spotlight table and the record source table, such as incident. Join the tables so that the Spotlight ID value matches the source record sys_id value. To view the latest Spotlight data, filter the list to show only active Spotlight records. The Spotlight for incident content pack includes a database view that joins the Spotlight and Incident tables. You can use it as an example to create your own database views to other tables. Previous topicCollect Spotlight scoresRelated conceptsDatabase viewsRelated referenceSpotlight for incident content pack On this page Send Feedback Previous Topic Next Topic


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Since it was established in 2002,Daho Meter has been specializing in density testing field on developing, innovating and producing. and has been devoting to provide densimeter with high precision, easy operation and good durability. Nowadays it is the most well-known professional densimeter brand in China after got great efforts for decades. It is the one can support a wideness of field including solid, porosity solid, powder, liquid., etc and other testing program related to density.Visit Store >
US $2089.45 / Piece
Quantity: 1
Shipping Cost: Free Shipping
To United States Via Ocean freight Est.Delivery Nov 20 and Nov 30
Type: Universal Testing Machine
Power: Electronic
Testing before delivery: yes
Usage: Universal Testing Machine
It is applicable for wide range of material for tension, compression, bending, shearing and low cycle test. Suitable for metal, rubber, plastic, spring, textile, and components testing.
ASTM, ISO, DIN, GB and other international standards.
3.Main Technical Parameters:
6.1 High strength main unit-------------------------------------------------------------------- ---------1 set
6.2 High precision arc synchronous deceleration system-------------------------------- ------1 suit
6.3 High precision ball screw---------------------------------------------------------------------- ----2pcs
6.4 Motor and Control system------------------------------------------------------------------------- 1 set
6.5 High precision load sensor-------------------------------------------------------------------------1 pc
6.6 High accuracy photoelectric encoder------------------------------------------------- ----------1 pc
6.7 Tensile fixture -----------------------------------------------------------------------------------------1 suit
6.8 LCD controller--------------------------------------------------------------------- -------------------1 set
6.9 Printer(optional)---------------------------------------------------------------------------------1 set
Please don't hesitate to contact us if you have any questions or concerns before or after your purchase. We are committed to your 100% satisfaction.
There are many payment methods available on DHgate.com such as credit cards, real-time bank transfers, offline payments (bank transfers). You can choose a method which is the most convenient for you. To protect your interests, your payment will be temporarily held by DHgate, and will not be released to us until you receive your order and are satisfied with it.
1.Shipping Cost:
Select the quantity first, then click the country via logistic methods in the page.
2.Go the the next page, you can see the detail shipping cost by each logistic methods under your selection.
3. Item Processing Time: The processing time for a specific order varies with the product type and stock status. Mostly, processing time can be 3 to 15 working days.
If you want to exchange the items received, you must contact us within 3 days of the receipt of your order. And you should pay the additional shipping fees incurred and the items returned should be kept in their original status.
Since your feedback is very important to our business`s development, we sincerely invite you to leave positive feedback for us if you are satisfied with our product and service. It`ll just take you 1 minute. Thank you!
Seller: dahometer
23 Transactions, 100% Positive Feedback
wholesale textile dyeing machine


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Nazarene Immigration Network Centers (NINC)
Front row-left to right - Teresa Stecker, Arlita Harris, Norma Gallegos, Pearl del Peret, Roger McCrummen
Second row - left to right - Margaret Scott, Sarah Bankard, Sarah Emerson
Third row - left to right - Tomas Alvarez, Alex Rodriguez, Joel Tooley
Back row - left to right - Josh Smith, Roberto Hodgson and Jonathan Fung
Dr. Robert Broadbooks gave a devotional and spoke on behalf of the Church of the Nazarene as the Regional Director of USA/CANADA. Dr. Nell Sweeden, Global NCM Director brought greetings to the group. In addition Immigration Lawyer Mr. Roger McCrummen spoke on the topic of Ethics and Immigration. Ms. Sarah Bankard the Capacity Building Specialist with World Relief gave an update on World Relief. Multicultural Ministries has partnered with World Relief to assist us in this area of ministry. In the afternoon, Rev. Stecker gave each center time to share about what their site is doing in this area of legal immigrant ministry and then the day was concluded by addressing common issues at each site and future follow up.
The Church of the Nazarene currently has six DOJ (Department of Justice) Recognized and Accredited sites and many others in the process of doing so. The process to become recognized and accredited is a lengthy process which nvolves a lot of planning, preparation and prayer. Remember in your prayers these sites and those who are seeking to reach out to the least, last and lost in a practical way in the name of Jesus.
For more information about this ministry contact Rev. Teresa Stecker at firstname.lastname@example.com or the Multicultural Ministries office at email@example.com.
Nazarene Legal Immigration Network Sites
IC Compassion - Iowa District
Hand in Hand, Missio Dei - Northwest District
Immigration Resource Center of San Gabriel Valley - Los Angeles District
Medford First Church of the Nazarene - Oregon Pacific District
Western Oaks Church of the Nazarene - Southwest Oklahoma District
Nazarene Centro de Refugio - Florida District
Immigration ABC - Washington Pacific District - Washington Pacific District