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Skeletal muscle depends on the precise orchestration of contractile and metabolic gene expression programs to direct fiber-type specification and to ensure muscle performance. Exactly how such fiber type-specific patterns of gene expression are established and maintained remains unclear, however. Here, we demonstrate that histone monomethyl transferase MLL4 (KMT2D), an enhancer regulator enriched in slow myofibers, plays a critical role in controlling muscle fiber identity as well as muscle performance. Skeletal muscle-specific ablation of MLL4 in mice resulted in downregulation of the slow oxidative myofiber gene program, decreased numbers of type I myofibers, and diminished mitochondrial respiration, which caused reductions in muscle fatty acid utilization and endurance capacity during exercise. Genome-wide ChIP-Seq and mRNA-Seq analyses revealed that MLL4 directly binds to enhancers and functions as a coactivator of the myocyte enhancer factor 2 (MEF2) to activate transcription of slow oxidative myofiber genes. Importantly, we also found that the MLL4 regulatory circuit is associated with muscle fiber-type remodeling in humans. Thus, our results uncover a pivotal role for MLL4 in specifying structural and metabolic identities of myofibers that govern muscle performance. These findings provide therapeutic opportunities for enhancing muscle fitness to combat a variety of metabolic and muscular diseases. [ABSTRACT FROM AUTHOR]

We assessed video directly observed therapy (VDOT) for monitoring tuberculosis treatment in 5 health districts in California, USA, to compare adherence between 174 patients using VDOT and 159 patients using in-person directly observed therapy (DOT). Multivariable linear regression analyses identified participant-reported sociodemographics, risk behaviors, and treatment experience associated with adherence. Median participant age was 44 (range 18-87) years; 61% of participants were male. Median fraction of expected doses observed (FEDO) among VDOT participants was higher (93.0% [interquartile range (IQR) 83.4%-97.1%]) than among patients receiving DOT (66.4% [IQR 55.1%-89.3%]). Most participants (96%) would recommend VDOT to others; 90% preferred VDOT over DOT. Lower FEDO was independently associated with US or Mexico birth, shorter VDOT duration, finding VDOT difficult, frequently taking medications while away from home, and having video-recording problems (p<0.05). VDOT cost 32% (range 6%-46%) less than DOT. VDOT was feasible, acceptable, and achieved high adherence at lower cost than DOT. [ABSTRACT FROM AUTHOR]

Background: Sagittal spinopelvic balance and proper sagittal alignment are important when planning corrective or reconstructive spinal surgery. Prior research suggests that people from different races and countries have moderate divergence; to the best of our knowledge, the population of Taiwan has not been studied with respect to this parameter.Questions/purposes: To investigate normal age- and sex-related differences in whole-spine sagittal alignment and balance of asymptomatic adults without spinal disorders.Methods: In this prospective study, we used convenience sampling to recruit asymptomatic volunteers who accompanied patients in the outpatient orthopaedic department. One hundred forty males with a mean age of 48 ± 19 years and 252 females with a mean age of 53 ± 17 years underwent standing lateral radiographs of the whole spine. For analysis, participants were divided in three groups by age (20 to 40 years, 41 to 60 years, and 61 to 80 years) and analyzed by sex (male and female). The following eight radiologic parameters were measured: sacral slope, pelvic tilt, pelvic incidence, thoracic kyphosis, lumbar lordosis, cervical lordosis, C2-C7 sagittal vertical axis, and C7-S1 sagittal vertical axis. Three observers performed estimations of the sagittal parameters twice, and the intraclass correlation coefficients for inter- and intraobserver variability were 0.81 and 0.83.Results: The mean pelvic incidence was 49° ± 12°; lumbar lordosis was smaller in the group that was 61 to 80 years old than in the groups that were 20 to 40 years and 41 to 60 years (95% CI of the difference, 4.50-13.64 and 1.00- 9.60; p < 0.001), while cervical lordosis was greater in the 61 to 80 years age group than the other two groups (95% CI of the difference, -14.64 to -6.57 and -11.57 to -3.45; p < 0.001). The mean C7-S1 sagittal vertical axis was 30 ± 29 mm, and there was no difference among the three groups and between males and females. Pelvic tilt was greater in the group 61 to 80 years old than the 20 to 40 years and 41 to 60 years age groups (95% CI of the difference, -10.81 to -5.42 and -7.15 to -2.08; p < 0.001), while sacral slope was larger in 61 to 80 years age group than in the 41 to 60 years group (95% CI of the difference, 0.79-6.25; p = 0.006). C7 slope was greater in 61 to 80 years age group than in the 20 to 40 years group (95% CI of the difference, -7.49 to -1.26; p = 0.002) and larger in 41 to 60 years age group than in 20 to 40 years group (95% CI of the difference, -6.31 to -0.05; p = 0.045). C2-C7 sagittal vertical axis was greater in males than in females (95% CI of the difference, 2.84-7.74; p < 0.001). C7 slope was negatively correlated with thoracic kyphosis (95% CI of the difference, -0.619 to 0.468; p < 0.001) and lumbar lordosis (95% CI of the difference, -0.356 to -0.223; p < 0.001), and positively correlated with pelvic incidence (95% CI of the difference, 0.058- 0.215; p < 0.001) and cervical lordosis (95% CI of the difference, 0.228 - 0.334; p < 0.001).Conclusions: Normal values of the spinopelvic sagittal parameters vary by age and sex in Taiwanese individuals.Clinical Relevance: Pelvic incidence and sacral slope observed in this population seemed smaller than those reported in other studies of white populations; this seems important when considering spine surgery in Taiwanese patients. Future studies should include collection of whole body sagittal parameters of larger and more-diverse populations, and assessments of patients with symptomatic spinal disorders. [ABSTRACT FROM AUTHOR]

Objectives: To assess the analgesic efficacy of transversus abdominis plane (TAP) block in patients undergoing colorectal surgery (CRS).Materials and Methods: The databases of PubMed, ISI Web of Science, and Embase were searched, and randomized controlled studies (RCTs) that compared TAP block to control for relief of postoperative pain in patients who underwent CRS were included. Outcomes, including postoperative pain at rest and with movement, morphine use, postoperative nausea and vomiting, and the length of hospital stay, were analyzed using STATA software. The weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) or relative risk with 95% CI were used to present the strength of associations.Results: A total of 7 RCTs with 511 patients were included. The results of this study suggested that TAP block significantly relieved postoperative pain during postanesthetic recovery after CRS at rest and during movement (WMDs were -0.98 [95% CI -1.57 to -0.38] and -0.68 [-1.07 to -0.30], respectively), and also decreased pain intensity during movement 24 h after CRS (WMD: -0.57 [95% CI -1.06 to -0.08]). TAP block significantly reduced opioid consumption within 24 h when compared to controls, with a WMD of 15.66 (95% CI -23.93 to -7.39). However, TAP block did not shorten the length of hospital stay.Conclusions: TAP block was an effective approach for relief of postoperative pain and reduced postoperative consumption of morphine. More RCTs with large sample sizes are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Importance: The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal. Previous studies have reached mixed conclusions regarding the association between calcium, vitamin D, or combined calcium and vitamin D supplements and fracture incidence in older adults.Objective: To investigate whether calcium, vitamin D, or combined calcium and vitamin D supplements are associated with a lower fracture incidence in community-dwelling older adults.Data Sources: The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to December 24, 2016, using the keywords calcium, vitamin D, and fracture to identify systematic reviews or meta-analyses. The primary randomized clinical trials included in systematic reviews or meta-analyses were identified, and an additional search for recently published randomized trials was performed from July 16, 2012, to July 16, 2017.Study Selection: Randomized clinical trials comparing calcium, vitamin D, or combined calcium and vitamin D supplements with a placebo or no treatment for fracture incidence in community-dwelling adults older than 50 years.Data Extraction and Synthesis: Two independent reviewers performed the data extraction and assessed study quality. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs), and 95% CIs using random-effects models.Main Outcomes and Measures: Hip fracture was defined as the primary outcome. Secondary outcomes were nonvertebral fracture, vertebral fracture, and total fracture.Results: A total of 33 randomized trials involving 51 145 participants fulfilled the inclusion criteria. There was no significant association of calcium or vitamin D with risk of hip fracture compared with placebo or no treatment (calcium: RR, 1.53 [95% CI, 0.97 to 2.42]; ARD, 0.01 [95% CI, 0.00 to 0.01]; vitamin D: RR, 1.21 [95% CI, 0.99 to 1.47]; ARD, 0.00 [95% CI, -0.00 to 0.01]. There was no significant association of combined calcium and vitamin D with hip fracture compared with placebo or no treatment (RR, 1.09 [95% CI, 0.85 to 1.39]; ARD, 0.00 [95% CI, -0.00 to 0.00]). No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration.Conclusions and Relevance: In this meta-analysis of randomized clinical trials, the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. These findings do not support the routine use of these supplements in community-dwelling older people. [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis aimed to compare the efficacy and safety of teriparatide vs. bisphosphonates in the management of osteoporosis.Methods: A total of 1,967 patients from eight randomized controlled trials were analyzed; outcomes included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine, vertebral and nonvertebral fractures and any adverse event. A subgroup analysis of treatment effectiveness was performed according to the etiology of osteoporosis; i.e., glucocorticoid-induced osteoporosis (GIO) vs. post-menopausal osteoporosis (PO).Results: Teriparatide increased the BMD of the lumbar spine, femoral neck and total hip to a greater extent than bisphosphonates. Patients treated with teriparatide also had a lower risk of vertebral fractures compared with bisphosphonates; however, no difference in risk of nonvertebral fractures (or adverse events) was found. GIO subgroups showed larger increases in BMD of the lumbar spine, total hip and femoral neck in patients treated with teriparatide compared with bisphosphonates. The PO subgroup showed larger increases in BMD of the lumbar spine in patients treated with teriparatide compared with bisphosphonates. Patients in the GIO subgroup (but not the PO subgroup) were less likely to suffer a vertebral fracture on teriparatide as compared with bisphosphonates. In contrast, no significant difference in the percentage of nonvertebral fractures was noted between the two types of treatment for either subgroup.Conclusion: Teriparatide significantly increased the BMD of lumbar spine, total hip and femoral neck, particularly in GIO-induced osteoporosis. Teriparatide did not lower the risk of nonvertebral fractures when compared with bisphosphonates. [ABSTRACT FROM AUTHOR]

Background: No systemic evaluation of asthma control in Jilin Province has been reported. Asthma control might provide the basis for asthma management in this region. A multicenter hospital-based cross-sectional study was performed to investigate the asthma control and related factors for severe asthma exacerbations in patients with moderate or severe asthma in Jilin Province, China.Methods: The study enrolled 1546 patients in five grade one general hospitals from January to December 2013. Asthma medication, patient self-management, asthma control test (ACT) scores and frequency of severe asthma exacerbations during the follow-up (12 months) were collected via a follow-up questionnaire.Results: In the study, 889 patients provided a complete follow-up questionnaire. Severe asthma exacerbations occurred in 54.89 % of patients. ACT score ≤15, asthma medication ≤ 3 months, severe asthma, income level lower than average Per Capita Disposable Income (PCDI) and a lower educational level were risk factors of a severe exacerbation.Conclusions: Poor adherence to asthma medication, poor asthma symptom control, lower income, a low educational level might be possible reasons for the high incidence of severe asthma exacerbations and poor asthma control in Jilin Province of China. [ABSTRACT FROM AUTHOR]

Low emotional support is associated with poor health outcomes. Engagement with face-to-face social networks is one way of increasing emotional support. However, it is not yet known whether engagement with proliferating electronic social networks is similarly associated with increased emotional support. Thus, the purpose of this study was to assess associations between social media use and perceived emotional support in a large, nationally-representative sample. In October 2014, we collected data from 1796 U.S. adults ages 19-32. We assessed social media use using both total time spent and frequency of visits to each of the 11 most popular social media platforms. Our dependent variable was perceived emotional support as measured by the brief Patient-Reported Outcomes Measurement Information System (PROMIS) emotional support scale. A multivariable model including all sociodemographic covariates and accounting for survey weights demonstrated that, compared with the lowest quartile of time on social media, being in the highest quartile (spending two or more hours per day) was significantly associated with decreased odds of having higher perceived emotional support (AOR 0.62, 95 % CI 0.40, 0.94). However, compared with those in the lowest quartile, being in the highest quartile regarding frequency of social media use was not significantly associated with perceived emotional support (AOR 0.70, 95 % CI 0.45, 1.09). In conclusion, while the cross-sectional nature of these data hinder inference regarding directionality, it seems that heavy users of social media may actually feel less and not more emotional support. [ABSTRACT FROM AUTHOR]

Background: Social media (SM) use is increasing among U.S. young adults, and its association with mental well-being remains unclear. This study assessed the association between SM use and depression in a nationally representative sample of young adults.Methods: We surveyed 1,787 adults ages 19 to 32 about SM use and depression. Participants were recruited via random digit dialing and address-based sampling. SM use was assessed by self-reported total time per day spent on SM, visits per week, and a global frequency score based on the Pew Internet Research Questionnaire. Depression was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Scale Short Form. Chi-squared tests and ordered logistic regressions were performed with sample weights.Results: The weighted sample was 50.3% female and 57.5% White. Compared to those in the lowest quartile of total time per day spent on SM, participants in the highest quartile had significantly increased odds of depression (AOR = 1.66, 95% CI = 1.14-2.42) after controlling for all covariates. Compared with those in the lowest quartile, individuals in the highest quartile of SM site visits per week and those with a higher global frequency score had significantly increased odds of depression (AOR = 2.74, 95% CI = 1.86-4.04; AOR = 3.05, 95% CI = 2.03-4.59, respectively). All associations between independent variables and depression had strong, linear, dose-response trends. Results were robust to all sensitivity analyses.Conclusions: SM use was significantly associated with increased depression. Given the proliferation of SM, identifying the mechanisms and direction of this association is critical for informing interventions that address SM use and depression. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking is associated with an increased risk of type 2 diabetes mellitus (T2DM). Smokers exhibit low circulating levels of total adiponectin (ADPN) and high-molecular-weight (HMW) ADPN multimers. Blood concentrations of HMW ADPN multimers closely correlate with insulin sensitivity for handling glucose. How tobacco smoke exposure lowers blood levels of ADPN, however, has not been investigated. In the current study, we examined the effects of tobacco smoke exposure in vitro and in vivo on the intracellular and extracellular distribution of ADPN and its HMW multimers, as well as potential mechanisms. Findings: We found that exposure of cultured adipocytes to tobacco smoke extract (TSE) suppressed total ADPN secretion, and TSE administration to mice lowered their plasma ADPN concentrations. Surprisingly, TSE caused intracellular accumulation of HMW ADPN in cultured adipocytes and in the adipose tissue of wild-type mice, while preferentially decreasing HMW ADPN in culture medium and in plasma. Importantly, we found that TSE up-regulated the ADPN retention chaperone ERp44, which colocalized with ADPN in the endoplasmic reticulum. In addition, TSE down-regulated DsbA-L, a factor for ADPN secretion. Conclusions: Tobacco smoke exposure traps HMW ADPN intracellularly, thereby blocking its secretion. Our results provide a novel mechanism for hypoadiponectinemia, and may help to explain the increased risk of T2DM in smokers. [ABSTRACT FROM AUTHOR]

Introduction: Perceived social isolation (PSI) is associated with substantial morbidity and mortality. Social media platforms, commonly used by young adults, may offer an opportunity to ameliorate social isolation. This study assessed associations between social media use (SMU) and PSI among U.S. young adults.Methods: Participants were a nationally representative sample of 1,787 U.S. adults aged 19-32 years. They were recruited in October-November 2014 for a cross-sectional survey using a sampling frame that represented 97% of the U.S.Population: SMU was assessed using both time and frequency associated with use of 11 social media platforms, including Facebook, Twitter, Google+, YouTube, LinkedIn, Instagram, Pinterest, Tumblr, Vine, Snapchat, and Reddit. PSI was measured using the Patient-Reported Outcomes Measurement Information System scale. In 2015, ordered logistic regression was used to assess associations between SMU and SI while controlling for eight covariates.Results: In fully adjusted multivariable models that included survey weights, compared with those in the lowest quartile for SMU time, participants in the highest quartile had twice the odds of having greater PSI (AOR=2.0, 95% CI=1.4, 2.8). Similarly, compared with those in the lowest quartile, those in the highest quartile of SMU frequency had more than three times the odds of having greater PSI (AOR=3.4, 95% CI=2.3, 5.1). Associations were linear (p<0.001 for all), and results were robust to all sensitivity analyses.Conclusions: Young adults with high SMU seem to feel more socially isolated than their counterparts with lower SMU. Future research should focus on determining directionality and elucidating reasons for these associations. [ABSTRACT FROM AUTHOR]