Chronic arthritides and bone structure: focus on rheumatoid arthritis-an update.

Normal bone remodeling depends of a balance between bone forming cells, osteoblasts and bone resorbing cells, the osteoclasts. In chronic arthritides and some inflammatory and autoimmune diseases such as rheumatoid arthritis, there is a great constellation of cytokines produced by pannus that impair bone formation and stimulate bone resorption by inducing osteoclast differentiation and inhibiting osteoblast maturation. Patients with chronic inflammation have multiple causes that lead to low bone mineral density, osteoporosis and a high risk of fracture including circulating cytokines, impaired mobility, chronic administration of glucocorticoids, low vitamin D levels and post-menopausal status in women, among others. Biologic agents and other therapeutic measures to reach prompt remission might ameliorate these deleterious effects. In many cases, bone acting agents need to be added to conventional treatment to reduce the risk of fractures and to preserve articular integrity and independency for daily living activities. A limited number of studies related to fractures in chronic arthritides were published, and future investigation is needed to determine the risk of fractures and the protective effects of different treatments to reduce this risk.

Estimation of body weight using body measurements in female water buffaloes reared in southeastern Mexico.

Buffalo farming is an important livestock activity in Mexico. However, the low technological level of the farms makes it difficult to monitor the growth rates of the animals. The objectives of this study were to analyse the body measurements of 107 adult female Murrah buffaloes, to estimate the interrelationships between those measurements and body weight, and to develop equations to predict body weight (BW) using body measurements including withers at height (WH), rump height (RH), body height (BH), heart girth (HG), abdominal girth (AG), pelvic girth (PG), body length (BL), girth circumference (GC), diagonal body length (DBL), pelvic circumference (PC), and abdomen circumference (AC). The study was conducted on two commercial farms in southern Mexico. Pearson correlation and stepwise regression techniques were used for the data analysis. To find out the best regression models, we used model quality criteria such as coefficient of determination (R2), adjusted R2 (Adj.R2), root mean square error (RMSE), Mallow's Cp, Akaike's information criteria (AIC), Bayesian information criteria (BIC), and coefficient of variation (CV). Correlation results indicated that BW had a positive high correlation (P < 0.01) of all the measured traits. Model 4 (-780.56 + 311.76GC + 383.51DBL + 51.82PC + 47.65AC-106.78BL) was the best regression model with a higher R2 (0.87), Adj. R2 (0.86) smaller Cp (4.24), AIC (749.19), BIC (752.16), and RMSE (36.91). The current study suggests that GC, DBL, PC, AC, and BL might be used in combination to estimate BW of adult female Murrah buffaloes.

Evidence based Latin American Guidelines of clinical practice on prevention, diagnosis, management and treatment of glucocorticoid induced osteoporosis. A 2022 update : This manuscript has been produced under the auspices of the Committee of National Societies (CNS) and the Committee of Scientific Advisors (CSA) of the International Osteoporosis Foundation (IOF).

Guidelines and recommendations developed and endorsed by the International Osteoporosis Foundation (IOF) are intended to provide guidance for particular pattern of practice for physicians who usually prescribe glucocorticoid (GC) therapy, and not to dictate the care of a particular patient. Adherence to the recommendations within this guideline is voluntary and the ultimate determination regarding their application should be made by the physician in light of each patient's circumstances. Guidelines and recommendations are intended to promote a desirable outcome but cannot guarantee any specific outcome. This guideline and its recommendations are not intended to dictate payment, reimbursement or insurance decisions. Guidelines and recommendations are subjected to periodic revisions as a consequence of the evolution of medicine, technology and clinical practice. A panel of Latin American (LATAM) experts specialized in osteoporosis with recognized clinical experience in managing patients with glucocorticoid-induced osteoporosis (GIO) met to produce evidence-based LATAM recommendations for the diagnosis and management of GIO. These guidelines are particularly intended to general practitioners and primary care physicians who prescribe GC treatments in LATAM to guide their daily clinical practice in terms of evaluation, prevention and treatment of GIO. These recommendations were based on systematic literature review using MEDLINE, EMBASE, SCOPUS and COCHRANE Library database during the period from 2012 to 2021. Randomized clinical trials (RCT), systematic reviews of RCT, controlled observational studies, guidelines and consensus were considered. Based on the review and expert opinion the panel members voted recommendations during two successive rounds of voting by panel members. Agreements for each statement were considered if a concordance of at least 70% was achieved following Delphi methodology. Grading of recommendations was made according to the Oxford Centre for the Evidence-based Medicine (EBM) criteria. Among five GIO guidelines and consensus initially identified, two of them (American College of Rheumatology 2017 and the Brazilian Guidelines 2021) were selected for comparison considering the latter as the most current guides in the LATAM region. Based on this methodology fifty statements were issued. All of them but four (1.20, 1.21, 1.23 and 4.2) attained agreement.

Models to predict live weight from heart girth in crossbred beef heifers.

The objective of this study was to develop and evaluate linear, quadratic, and exponential mathematical models to predict live weight (LW) from heart girth (HG) in crossbred heifers raised in tropical humid conditions in Mexico. Live weight (363.32 ± 150.88 kg) and HG (166.83 ± 24.88 cm) were measured in 400 heifers aged between 3 and 24 months. Linear and non-linear regression was used to construct the prediction models. The goodness of fit of the models was evaluated using the Akaike information criterion (AIC), the Bayesian information criterion (BIC), coefficient of determination (R2), mean squared error (MSE), and root MSE (RMSE). In addition, the developed models were evaluated through internal and external cross-validation (k-folds) using independent data. The ability of the fitted models to predict the observed values was evaluated based on the root mean square error of prediction (RMSEP), R2, and mean absolute error (MAE). The correlation coefficient between LW and HG was r = 0.98 (P < 0.001). The quadratic model showed the lowest values of MAE (736.57), RMSEP (27.13), AIC (3783.95), and BIC (3799.91). Additionally, this model exhibited better goodness-of-fit values regarding external and internal validation criteria (higher R2 and lower RMSEP and MAE), thus having better predictive performance. The RMSE represented about 8% of the observed LW. Heart girth is highly correlated (r = 0.98) with LW. The quadratic model showed a high predictive capacity for crossbred heifers kept in tropical conditions.

Calpain 3 and CaMKIIß signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy.

Mutations in CAPN3 cause autosomal recessive limb girdle muscular dystrophy 2A. Calpain 3 (CAPN3) is a calcium dependent protease residing in the myofibrillar, cytosolic and triad fractions of skeletal muscle. At the triad, it colocalizes with calcium calmodulin kinase IIß (CaMKIIß). CAPN3 knock out mice (C3KO) show reduced triad integrity and blunted CaMKIIß signaling, which correlates with impaired transcriptional activation of myofibrillar and oxidative metabolism genes in response to running exercise. These data suggest a role for CAPN3 and CaMKIIß in gene regulation that takes place during adaptation to endurance exercise. To assess whether CAPN3- CaMKIIß signaling influences skeletal muscle remodeling in other contexts, we subjected C3KO and wild type mice to hindlimb unloading and reloading and assessed CaMKIIß signaling and gene expression by RNA-sequencing. After induced atrophy followed by 4 days of reloading, both CaMKIIß activation and expression of inflammatory and cellular stress genes were increased. C3KO muscles failed to activate CaMKIIß signaling, did not activate the same pattern of gene expression and demonstrated impaired growth at 4 days of reloading. Moreover, C3KO muscles failed to activate inducible HSP70, which was previously shown to be indispensible for the inflammatory response needed to promote muscle recovery. Likewise, C3KO showed diminished immune cell infiltration and decreased expression of pro-myogenic genes. These data support a role for CaMKIIß signaling in induction of HSP70 and promotion of the inflammatory response during muscle growth and remodeling that occurs after atrophy, suggesting that CaMKIIß regulates remodeling in multiple contexts: endurance exercise and growth after atrophy.

CHC22 and CHC17 clathrins have distinct biochemical properties and display differential regulation and function.

Clathrins are cytoplasmic proteins that play essential roles in endocytosis and other membrane traffic pathways. Upon recruitment to intracellular membranes, the canonical clathrin triskelion assembles into a polyhedral protein coat that facilitates vesicle formation and captures cargo molecules for transport. The triskelion is formed by trimerization of three clathrin heavy-chain subunits. Most vertebrates have two isoforms of clathrin heavy chains, CHC17 and CHC22, generating two clathrins with distinct cellular functions. CHC17 forms vesicles at the plasma membrane for receptor-mediated endocytosis and at the trans-Golgi network for organelle biogenesis. CHC22 plays a key role in intracellular targeting of the insulin-regulated glucose transporter 4 (GLUT4), accumulates at the site of GLUT4 sequestration during insulin resistance, and has also been implicated in neuronal development. Here, we demonstrate that CHC22 and CHC17 share morphological features, in that CHC22 forms a triskelion and latticed vesicle coats. However, cellular CHC22-coated vesicles were distinct from those formed by CHC17. The CHC22 coat was more stable to pH change and was not removed by the enzyme complex that disassembles the CHC17 coat. Moreover, the two clathrins were differentially recruited to membranes by adaptors, and CHC22 did not support vesicle formation or transferrin endocytosis at the plasma membrane in the presence or absence of CHC17. Our findings provide biochemical evidence for separate regulation and distinct functional niches for CHC17 and CHC22 in human cells. Furthermore, the greater stability of the CHC22 coat relative to the CHC17 coat may be relevant to its excessive accumulation with GLUT4 during insulin resistance.

Preliminary human health risk assessment of arsenic and fluoride in tap water from Zacatecas, México.

Zacatecas state is located in the central area of Mexico, where the underground water contains elevated quantities of natural arsenic and fluoride. In order to estimate health risk associated with human exposure to these pollutants, tap water samples from the southern-central region of the state were analyzed. Ninety percent of the samples exceeded the levels of arsenic established by the World Health Organization (WHO) of 0.01 mg/L and 43 % exceeded the limit established by the NOM-127-SSA1(1) of 0.025 mg/L. Forty-three percent of the samples had fluoride levels above the Mexican regulation limit of 1.5 mg/L (NOM-127-SSA1). We used WHO and EPA's health risk assessment method, we estimated 80 % of the inhabitants of sites studied could be exposed to arsenic levels higher than those recommended by EPA and the WHO, 22 % could be exposed to fluoride levels higher than those recommended by EPA, and 16 % of the local population may be in risk of suffering dental fluorosis.

Listening to Fast-Tempo Music Improves Physical Performance in Recreational Swimmers.

Purpose: To determine whether swimming while listening to fast (140 bpm) or moderate tempo (120 bpm) music enhances physical performance compared to a non-music condition. Methods: Sixteen healthy university students (21.5 ± 2.3 years) with a minimum of one year of experience swimming front crawl were recruited. All completed four testing sessions. In the first session, a graded exercise treadmill test was performed to establish baseline fitness. The next three visits were at the swimming pool and participants were asked to swim as far as possible in 12-minutes (i.e., Swimming Cooper Test) under each of three randomly assigned conditions: 120 bpm (M120), 140 bpm (M140) and a non-music condition (NM). Results: No significant differences were found between conditions for either heart rate (p > .05) or rating of perceived exertion (p > .05). However, differences were found on distance covered (p = .014) between M120 (305.7 ± 19.7 m) and M140 (321.2 ± 19.4 m; p = .035), and on stroke frequency (p = .009) between M120 (48.4 ± 1.8) and M140 (51.6 ± 1.9; p = .028). Conclusion: These results suggest that distance covered and the frequency of strokes per minute were greater when participants were exposed to fast tempo music (M140) compared to moderate tempo music (M120) and a non-music condition (NM) in a 12-minute swimming test.

Melatonin therapy reverses lead exposure-induced testicular damage in rats despite the lack of effect on serum testosterone levels.

Lead (Pb) exposure induces testicular damage and infertility. The aim of this study was to analyze and compare the therapeutic effects of antioxidants or vitamin D and calcium, which have previously been shown to reduce the toxic effects of Pb co-exposure, in rats. Rats were exposed to Pb for 28 days and subsequently treated with antioxidant (melatonin, silymarin), vitamin D and calcium (VitDCa) or a combination (melatonin or silymarin with VitDCa) for 28 days. Control groups included untreated rats (no Pb exposure or therapy), rats exposed only to melatonin or silymarin and rats exposed to Pb without post exposure therapy. Pb exposure induced testicular damage, increased blood lead level (BLL) and reduced serum testosterone level (STL). Rats exposed to Pb and left untreated for 28 days showed persistent pathological testicular alterations. The two treatments that were most effective in reversing pathological testis damage and restoring spermatogenesis were melatonin and silymarin. However, silymarin and melatonin treatment resulted in significantly different serum testosterone levels in rats. Whereas melatonin therapy reduced serum testosterone to levels lower than those in control rats, silymarin increased serum testosterone to levels higher than those in controls. Our pathological analysis of testes revealed that melatonin promoted spermatogenesis and regression of Pb exposure-induced degenerative changes, despite the associated reduction in serum testosterone levels. This result suggests that circulating testosterone may not have an important role in spermatogenesis. Collectively, our results suggest that melatonin and silymarin are effective therapies against the toxic effects Pb exposure in the male reproductive system.

Microplastics in sediments from the southern Gulf of Mexico: Abundance, distribution, composition, and adhered pollutants.

Approximately 23 Mt of plastics reaches the ocean each year, fragmented into microplastics (MP). MPs are widely dispersed in the sea, becoming deposited in sediments. MPs are considered carriers of pollutants such as heavy metals and polycyclic aromatic hydrocarbons and, when ingested by biota, pose a high health risk. This study determined metals and PAHs in sedimentary microplastics from the southern Gulf of Mexico (GOM). One hundred twenty-four sediment samples were collected, covering an area of 26,220 km2. The mean (±SD) of MPs in sediments was 16.46 ± 17.76 MPs/kg. The most abundant polymers were cellophane (CE), polyvinylidene fluoride (PVDF), polyethylene (PE), polyamides (PA), and nylon (NYL). A strong correlation (r: 0.83) was found between MP density and sediment depth. PA and PE were found near shorelines and PVDF near oil platforms. Aluminum, arsenic, and tin had the highest concentration (89.6 ± 94.6, 23.1 ± 70.3, and 19 ± 29.2 µg g-1, respectively), and acenaphthylene was the PAH with the highest concentration (3.4 ± 12.6 µg g-1). This study shows that MP with a higher density is found at greater depths, and this research is one of the first to cover a large area of the Gulf of Mexico.

First report and risk of infection of Fasciola hepatica (Linnaeus, 1761) in water buffaloes (Bubalus bubalis - Linnaeus, 1758) in Mexico.

The aim of this study was to determine the prevalence and risk of Fasciola hepatica infection in water buffaloes (Bubalus bubalis) during peripartum in southeastern Mexico. An observational study was designed, in which 94 pregnant buffalo cows near calving and naturally exposed to F. hepatica were included. Farm visits were made on days 60, 30, 15 prepartum, at calving, and on days 15 and 30 postpartum. Feces were obtained from all animals to confirm the presence of F. hepatica eggs. A group of 49 animals was randomly treated twice at day 60 prepartum and at calving with nitroxynil and the other group (n = 45) was kept untreated. Buffaloes would be treated once presenting a positive coproparasitological diagnosis up to 30 days postpartum. F. hepatica was detected in 5.3% of the buffaloes (5/94) with a prevalence between 1.7 and 12%. It was observed that treated buffaloes had a lower risk (4.08%) of being positive than untreated buffaloes (6.67%) (P > 0.05). It was also found that untreated animals had 1.6 times more risk of being positive than treated buffaloes. This paper presents the first report of F. hepatica in water buffaloes in Mexico, demonstrating that the two preventive treatments reduced F. hepatica egg shedding during parturition. These findings highlight the need for monitoring for F. hepatica even in unreported/silent potential disease areas.

Teleneurology clinics for polyneuropathy: a pilot study.

INTRODUCTION: Polyneuropathy (PN) is a common condition with significant morbidity. We developed tele-polyneuropathy (tele-PN) clinics to improve access to neurology and increase guideline-concordant PN care. This article describes the mixed-methods evaluation of pilot tele-PN clinics at three community sites within the Greater Los Angeles VA Healthcare System. METHODS: For the first 25 patients (48 scheduled visits), we recorded the duration of the tele-PN visit and exam; the performance on three guideline-concordant care indicators (PN screening labs, opiate reduction, physical therapy for falls); and patient-satisfaction scores. We elicited comments about the tele-PN clinic from patients and the clinical team. We combined descriptive statistics with qualitative themes to determine the feasibility and acceptability of the tele-PN clinics. RESULTS: The average tele-PN encounter and exam times were 28.5 and 9.1 min, respectively. PN screening lab completion increased from 80 to 100%. Opiate freedom improved from 68 to 88%. Physical therapy for patients with recent falls increased from 58 to 100%. The tele-PN clinic was preferred for follow-up over in-person clinics in 86% of cases. Convenience was paramount to the clinic's success, saving an average of 231 min per patient in round-trip travel. The medical team's caring and collaborative spirit received high praise. While the clinic's efficiency was equal or superior to in-person care, the limited treatment options for PN and the small clinical exam space are areas for improvement. CONCLUSION: In this pilot, we were able to efficiently see and examine patients remotely, promote guideline-concordant PN care, and provide a high-satisfaction encounter.

Indoor air pollution in a Mexican indigenous community: evaluation of risk reduction program using biomarkers of exposure and effect.

Indoor air pollution can be an important risk factor for human health, considering that people spend more than 60% of their time indoors. Fifty percent of the world population and approximately 90% of the rural population in developing countries are using biomass as energy source. Latin America represents 12% of the global consumption of biomass; in Mexico, 27 million people use wood as an energy source. Therefore, in this study we evaluated a 3-stage risk reduction program. The stages were: 1) removal of indoor soot adhered to roofs and internal walls; 2) paving the dirt floors; and 3) introduction of a new wood stove with a metal chimney that expels smoke outdoors. The complete intervention program was applied. In 20 healthy subject residents from an indigenous community in San Luis Potosí, Mexico, we measured blood carboxyhemoglobin (% COHb), DNA damage (comet assay) in nucleated blood cells, and urinary 1-OHP levels before and after the program. Before intervention individuals had a geometric mean COHb level of 4.93% and 53% of the population presented levels above 2.5% considered a safe level. However, in all the studied individuals the levels of COHb were reduced to below 2.5% (mean level 1.0%) one month after the intervention. Moreover, when compared, DNA damage in people exposed before the intervention was higher (5.8+/-1.3 of Tail Moment) than when the program was introduced (2.8+/-0.9 of Tail Moment) (P>0.05) and a same trend was observed with urinary 1-OHP levels; 6.71+/-3.58 micromol/mol creatinine was the concentration before intervention; whereas, 4.80+/-3.29 micromol/mol creatinine was the one after the program. The results suggest that the intervention program offers an acceptable risk reduction to those families that use biomass for food cooking.

Environmental Epigenetic Changes, as Risk Factors for the Development of Diseases in Children: A Systematic Review.

BACKGROUND: Children are susceptible to environmental contaminants and are at risk of developing diseases, more so if the exposure begins at an early age. Epidemiological studies have postulated the hypothesis of the fetal origin of disease, which is mediated by epigenetic changes. Epigenetic marks are inheritable; they modulate the gene expression and can affect human health due to the presence of environmental factors. OBJECTIVE: This review focuses on DNA-methylation and its association with environmental-related diseases in children. METHODS: A search for studies related to DNA-methylation in children by pre- or post-natal environmental exposures was conducted, and those studies with appropriate designs and statistical analyses and evaluations of the exposure were selected. FINDINGS: Prenatal and early life environmental factors, from diet to exposure to pollutants, have been associated with epigenetic changes, specifically DNA-methylation. Thus, maternal nutrition and smoking and exposure to air particulate matter, polycyclic aromatic hydrocarbons, arsenic, heavy metals, persistent organic pollutants, and some endocrine disrupters during pregnancy have been associated with genomic and gene-specific newborns' DNA-methylation changes that have shown in some cases sex-specific patterns. In addition, these maternal factors may deregulate the placental DNA-methylation balance and could induce a fetal reprogramming and later-in-life diseases. CONCLUSIONS: Exposure to environmental pollutants during prenatal and early life can trigger epigenetic imbalances and eventually the development of diseases in children. The integration of epigenetic data should be considered in future risk assessments.

Association of Dietary Advanced Glycation End Products with Metabolic Syndrome in Young Mexican Adults.

Background: Consumption of dietary advanced glycation end products is linked to metabolic syndrome. The objective was to describe the association between dietary advanced glycation end products intake and metabolic syndrome in young Mexican adults. Methods: The present was a cross-sectional study in 126 Mexican adults 18⁻35 years old evaluating metabolic syndrome through the harmonized criteria. Macronutrients and dietary advanced glycation end products intake were estimated through three 24-hour dietary recalls and food composition tables. Association between metabolic syndrome and high advanced glycation end products intake (≥10,000 kU/day) was evaluated through three logistic regression models adjusted by sex, age, family history of cardiometabolic diseases and energy intake. Results: Subjects with a higher advanced glycation end products intake were more likely to have impaired fasting glucose (OR: 4.91, 95% CI 1.29⁻18.60, p < 0.05) and metabolic syndrome (OR: 2.67, 95% CI 0.96⁻7.44, p = 0.059) than those participants with low consumption of these products after adjustment of sex, age, family history of cardiovascular disease and energy intake. Conclusions: High intake of dietary advanced glycation end products was significantly associated with impaired fasting glucose and marginally with metabolic syndrome in young Mexican adults regardless of sex, age, family history of cardiovascular disease and energy intake.

The surface protein Pvs25 of Plasmodium vivax ookinetes interacts with calreticulin on the midgut apical surface of the malaria vector Anopheles albimanus.

Malaria parasite transmission-blocking control strategies within the mosquito vector require an adequate understanding of the parasite mosquito interaction at the molecular level. The ookinete P25-P28 surface proteins are required for the transition from ookinete to oocyst in the mosquito midgut; however, their respective molecular interactions in the mosquito are largely unknown. We used recombinant Pvs25 and Pvs28 as probes for identification of potential Anopheles albimanus midgut ligands. A 50 kDa protein interacted with Pvs25 but not with Pvs28 in blot overlay assays. This protein was identified as calreticulin by LS MS and was detected in membrane, but not in soluble midgut protein extracts. Calreticulin was detected in An. albimanus midgut microvilli by immunofluorescence analysis. The An. albimanus calreticulin cDNA was cloned and recombinant calreticulin was shown to interact with recombinant Pvs25 in overlay and co-immunoprecipitation assays, confirming the interaction of the two proteins. The Pvs25-calreticulin interaction in vivo could represent a potential target for developing transmission blocking strategies based on interfering the parasite-midgut interaction.

Hematologic RIs for healthy water buffaloes (Bubalus bubalis) in southern Mexico.

BACKGROUND: Baseline hematologic data are used by veterinarians and wildlife biologists to perform health assessments on target animal species. Hematologic measurements are influenced by various factors including geography. Baseline hematologic RIs have been established for domestic water buffaloes (Bubalus bubalis) from various countries in the Eastern Hemisphere, but these data are not readily available for the Western Hemisphere. OBJECTIVE: The aim of this study was to determine hematologic values for domestic water buffaloes from several commercial farms in southern Mexico. METHODS: Blood was collected from 126 healthy, postlactating females (3 to 10 years old) from the Murrah breed, and 10 hematologic variables were measured. RESULTS: Means, SDs, RIs, medians (MED), median absolute deviations (MAD), and other statistics were calculated for each hematologic variable. The MED (and MAD) for each variable are as follows: RBC count, 7.6 (1.1) × 1012 /L; hemoglobin, 116.0 (13.3) g/L; PCV, 41.5 (7.6) %; MCV, 56.8 (7.0) fL; MCH, 14.6 (1.6) pg; MCHC, 250.0 (35.6) g/L; RDW (SD), 29.7 (5.5) fL; RDW (CV), 18.2 (1.4) %; reticulocytes, 0.0 (0.0) %, and WBC count, 12.4 (1.3) × 109 /L. These values were compared to those previously reported for water buffaloes from several countries in the Eastern Hemisphere and, on most occasions, they differed significantly. CONCLUSIONS: Our data can be used by veterinarians and other personnel involved in buffalo production in Mexico during medical evaluations.

Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis PotosÍ and León, México.

This research was designed to analyze the possible associations of Arg389Gly ADRB1 and Trp64Arg ADRB3 polymorphisms in children with obesity. A cross-sectional study included 1,046 school-age Mexican participants (6-12 years old) from the cities of San Luis PotosÍ and León. Children were classified as non-obese or obese according to their body mass index (BMI) percentile; obese children had a BMI≥95th percentile for sex and age. Biochemical data were collected. Polymorphisms were detected using TaqMan qPCR assay. A logistic regression analysis was used to calculate the risk of obesity based on genotypes. Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, LDL-cholesterol, triglycerides, and lower HDL-cholesterol compared with the normal weight group (P<0.05). The distribution of allele frequency in the population was Arg= 87.4 and Gly= 12.6 (Hardy Weinberg equilibrium c2 = 3.16 , P = 0.07 ); Trp= 81.5 and Arg= 18.5 (Hardy Weinberg equilibrium c2 = 2.2, P = 0.14 ) for ADRB1 and ADRB3, respectively. Even though no different frequencies of Arg389Gly polymorphism between groups were found (P = 0.08), children carriers of one Gly389 ADRB1 allele had a risk for obesity of OR=1.40 (95%CI, 1.03-1.90, P = 0.03) after adjustment for age and gender. No other association was found for Trp64Arg ADRB3 polymorphism. Only the Arg389Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

Clathrin light chains are required for the gyrating-clathrin recycling pathway and thereby promote cell migration.

The clathrin light chain (CLC) subunits participate in several membrane traffic pathways involving both clathrin and actin, through binding the actin-organizing huntingtin-interacting proteins (Hip). However, CLCs are dispensable for clathrin-mediated endocytosis of many cargoes. Here we observe that CLC depletion affects cell migration through Hip binding and reduces surface expression of ß1-integrin by interference with recycling following normal endocytosis of inactive ß1-integrin. CLC depletion and expression of a modified CLC also inhibit the appearance of gyrating (G)-clathrin structures, known mediators of rapid recycling of transferrin receptor from endosomes. Expression of the modified CLC reduces ß1-integrin and transferrin receptor recycling, as well as cell migration, implicating G-clathrin in these processes. Supporting a physiological role for CLC in migration, the CLCb isoform of CLC is upregulated in migratory human trophoblast cells during uterine invasion. Together, these studies establish CLCs as mediating clathrin-actin interactions needed for recycling by G-clathrin during migration.

The CHC22 clathrin-GLUT4 transport pathway contributes to skeletal muscle regeneration.

Mobilization of the GLUT4 glucose transporter from intracellular storage vesicles provides a mechanism for insulin-responsive glucose import into skeletal muscle. In humans, clathrin isoform CHC22 participates in formation of the GLUT4 storage compartment in skeletal muscle and fat. CHC22 function is limited to retrograde endosomal sorting and is restricted in its tissue expression and species distribution compared to the conserved CHC17 isoform that mediates endocytosis and several other membrane traffic pathways. Previously, we noted that CHC22 was expressed at elevated levels in regenerating rat muscle. Here we investigate whether the GLUT4 pathway in which CHC22 participates could play a role in muscle regeneration in humans and we test this possibility using CHC22-transgenic mice, which do not normally express CHC22. We observed that GLUT4 expression is elevated in parallel with that of CHC22 in regenerating skeletal muscle fibers from patients with inflammatory and other myopathies. Regenerating human myofibers displayed concurrent increases in expression of VAMP2, another regulator of GLUT4 transport. Regenerating fibers from wild-type mouse skeletal muscle injected with cardiotoxin also showed increased levels of GLUT4 and VAMP2. We previously demonstrated that transgenic mice expressing CHC22 in their muscle over-sequester GLUT4 and VAMP2 and have defective GLUT4 trafficking leading to diabetic symptoms. In this study, we find that muscle regeneration rates in CHC22 mice were delayed compared to wild-type mice, and myoblasts isolated from these mice did not proliferate in response to glucose. Additionally, CHC22-expressing mouse muscle displayed a fiber type switch from oxidative to glycolytic, similar to that observed in type 2 diabetic patients. These observations implicate the pathway for GLUT4 transport in regeneration of both human and mouse skeletal muscle, and demonstrate a role for this pathway in maintenance of muscle fiber type. Extrapolating these findings, CHC22 and GLUT4 can be considered markers of muscle regeneration in humans.