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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]

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]

Long noncoding RNAs (lncRNAs) are transcribed RNAs with more than 200 nucleotides in length. A growing body of evidence supports the notion that lncRNAs act as competitive endogenous RNAs for microRNAs and play roles in physiological and pathological processes. Several studies have demonstrated the roles of microRNAs in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, it is unknown whether lncRNAs are involved in IPF. To investigate the roles of lncRNAs in IPF, we determined the interaction of lncRNAs and microRNAs by motif search and manual comparison. The sequences of the dysregulated microRNAs in IPF including miR-21, miR-31, miR-101, miR- 29, miR-199, and let-7d were used to search NONCODE database containing 33,829 human lncRNAs. A total of 34 lncRNAs with potential binding sites to these microRNAs were identified. We then examined the expression levels of the identified lncRNAs in the lungs of IPF patients by real-time PCR. Of 34 lncRNAs, nine lncRNAs were dysregulated in the IPF lungs. Four of them were inversely correlated to the microRNA expression in IPF. Further studies revealed that silencing the lncRNA CD99 molecule pseudogene 1 (CD99P1) inhibited proliferation and α-smooth muscle actin expression of lung fibroblasts, while knockdown of the lncRNA n341773 increased collagen expression in lung fibroblasts. These results suggest that CD99P1 and n341773 may be involved in the regulation of lung fibroblast proliferation and differentiation. The identification of regulatory functions of lncRNAs in lung fibroblasts may provide new research directions for the therapy of IPF. [ABSTRACT FROM AUTHOR]

Objective: Given the observed differences in alcohol consumption characteristics between the Han and Uyghur nationalities in clinical reports and in daily life, the subjective and objective responses to alcohol in heavy drinkers (HDs) and light drinkers (LDs) in the Han and Uyghur nationalities in China were compared. Methods: A within-subject, double-blind, placebo-controlled human laboratory paradigm was performed. Each subject completed three experimental sessions in random order. Biphasic Alcohol Effects Scale and Positive and Negative Affect Schedule scales were administered, and heart rate (HR), blood pressure, and salivary cortisol levels were measured at predrink baseline and 30, 60, 120, and 180 minutes after the initial alcohol beverage consumption. Results: Compared with LDs, HDs exhibited higher stimulation, positive affect, and lower sedation in both ethnicities. Han drinkers (both HDs and LDs) exhibited higher sedation and lower positive affect and stimulation than Uyghur drinkers after consumption of alcohol. Moreover, HDs exhibited more HR increase during the ascending limb of breath alcohol content (p < .05) and less cortisol level during the declining limb of breath alcohol content (p < .05). Both HDs and LDs exhibited decreased systolic and diastolic pressures for both high- and low-dose beverages (ps < .01). Conclusion: Compared with LDs, HDs exhibited more HR increase and lower salivary cortisol level after alcohol consumption. Han drinkers (both HDs and LDs) exhibited higher sedation and lower positive affect and stimulation after consumption of alcohol as compared with Uyghur drinkers. This modality of subjective and physiological responses to alcohol in the Han and Uyghur ethnicities is similar. [ABSTRACT FROM AUTHOR]

Background To compare the clinical outcomes of external fixator (EF) and intramedullary nails (IN) in the treatment of open tibial fractures. Methods We searched seven electronic databases (PubMed, MEDLINE, EMBASE, OVID, Cochrane library, CNKI, and CBM) for trials of tibial fracture fixation published from 1980 to 2013. The indicators including postoperative infection, malunion, nonunion, soft tissue injury, delayed healing, and healing time were used for quantitative outcome assessments. Results A total of nine trials involving 532 patients (EF, n = 253; IN, n = 279) with open tibia fractures were included in this meta-analysis. The results indicated that the patients undergoing IN had lower incidence of postoperative infection (risk radio [RR] = 3.85; 95% confidence intervals [CI], 2.67-5.54; P < 0.0001), malunion (RR = 2.31; 95% CI, 1.40-3.81; P = 0.001), nonunion (RR = 1.41; 95% CI, 1.06-1.88; P = 0.02) and less healing time (weighted mean difference [WMD] = 6.19; 95% CI, 1.42-10.96; P = 0.01) compared with EF. However, regarding to the soft tissue injury (RR = 0.74; 95% CI, 0.34-1.62; P = 0.45) and delayed healing (RR = 1.38; 95% CI, 0.79-2.43; P = 0.26), there is no significantly difference between EF and IN approach. Conclusion In conclusion, the use of IN is more effective than EF and may be considered as first-line approach in fixation of open tibial fractures. [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]