Structural basis of TFIIH activation for nucleotide excision repair.

Nucleotide excision repair (NER) is the major DNA repair pathway that removes UV-induced and bulky DNA lesions. There is currently no structure of NER intermediates, which form around the large multisubunit transcription factor IIH (TFIIH). Here we report the cryo-EM structure of an NER intermediate containing TFIIH and the NER factor XPA. Compared to its transcription conformation, the TFIIH structure is rearranged such that its ATPase subunits XPB and XPD bind double- and single-stranded DNA, consistent with their translocase and helicase activities, respectively. XPA releases the inhibitory kinase module of TFIIH, displaces a 'plug' element from the DNA-binding pore in XPD, and together with the NER factor XPG stimulates XPD activity. Our results explain how TFIIH is switched from a transcription to a repair factor, and provide the basis for a mechanistic analysis of the NER pathway

Characteristics of randomized controlled trials of yoga: A bibliometric analysis

© 2014 Cramer et al.; licensee BioMed Central Ltd. Background: A growing number of randomized controlled trials (RCTs) have investigated the therapeutic value of yoga interventions. This bibliometric analysis aimed to provide a comprehensive review of the characteristics of the totality of available randomized yoga trials. Methods: All RCTs of yoga were eligible. Medline/PubMed, Scopus, the Cochrane Library, IndMED, and the tables of content of yoga specialty journals not listed in medical databases were screened through February 2014. Bibliometric data, data on participants, and intervention were extracted and analyzed descriptively. Results: Published between 1975 and 2014, a total of 366 papers were included, reporting 312 RCTs from 23 different countries with 22,548 participants. The median study sample size was 59 (range 8-410, interquartile range = 31, 93). Two hundred sixty-four RCTs (84.6%) were conducted with adults, 105 (33.7%) with older adults and 31 (9.9%) with children. Eighty-four RCTs (26.9%) were conducted with healthy participants. Other trials enrolled patients with one of 63 varied medical conditions; the most common being breast cancer (17 RCTs, 5.4%), depression (14 RCTs, 4.5%), asthma (14 RCTs, 4.5%) and type 2 diabetes mellitus (13 RCTs, 4.2%). Whilst 119 RCTs (38.1%) did not define the style of yoga used, 35 RCTs (11.2%) used Hatha yoga and 30 RCTs (9.6%) yoga breathing. The remaining 128 RCTs (41.0%) used 46 varied yoga styles, with a median intervention length of 9 weeks (range 1 day to 1 year; interquartile range = 5, 12). Two hundred and forty-four RCTs (78.2%) used yoga postures, 232 RCTs (74.4%) used breath control, 153 RCTs (49.0%) used meditation and 32 RCTs (10.3%) used philosophy lectures. One hundred and seventy-four RCTs (55.6%) compared yoga with no specific treatment; 21 varied control interventions were used in the remaining RCTs. Conclusions: This bibliometric analysis presents the most complete up-to-date overview on published randomized yoga trials. While the available research evidence is sparse for most conditions, there was a marked increase in published RCTs in recent years

A Systematic Review and Meta-Analysis Estimating the Expected Dropout Rates in Randomized Controlled Trials on Yoga Interventions

© 2016 Holger Cramer et al. A reasonable estimation of expected dropout rates is vital for adequate sample size calculations in randomized controlled trials (RCTs). Underestimating expected dropouts rates increases the risk of false negative results while overestimating rates results in overly large sample sizes, raising both ethical and economic issues. To estimate expected dropout rates in RCTs on yoga interventions, MEDLINE/PubMed, Scopus, IndMED, and the Cochrane Library were searched through February 2014; a total of 168 RCTs were meta-analyzed. Overall dropout rate was 11.42% (95% confidence interval [CI] = 10.11%, 12.73%) in the yoga groups; rates were comparable in usual care and psychological control groups and were slightly higher in exercise control groups (rate = 14.53%; 95% CI = 11.56%, 17.50%; odds ratio = 0.82; 95% CI = 0.68, 0.98; p = 0.03). For RCTs with durations above 12 weeks, dropout rates in yoga groups increased to 15.23% (95% CI = 11.79%, 18.68%). The upper border of 95% CIs for dropout rates commonly was below 20% regardless of study origin, health condition, gender, age groups, and intervention characteristics; however, it exceeded 40% for studies on HIV patients or heterogeneous age groups. In conclusion, dropout rates can be expected to be less than 15 to 20% for most RCTs on yoga interventions. Yet dropout rates beyond 40% are possible depending on the participants' sociodemographic and health condition

Complementary Medicine Use and Uptake of Cancer Screening Among US Adults: A Nationally Representative Cross-Sectional Survey.

Background: Cancer screenings can considerably reduce cancer mortality. There is limited information on the association between complementary medicine use and adherence to recommended cancer screenings. In this study, the potential associations between uptake of cancer screening and consultations with complementary medicine practitioners or mind-body medicine use are examined. Methods: This is a cross-sectional analysis of the 2017 National Health Interview Survey of a population-based sample (n = 26 742; response rate = 80.7%). Age- and sex-related risk groups for breast cancer (women 45 years and older), cervical cancer (women 21 years and older), and colorectal cancer (45 to 85 years) were analyzed in 2018. Prevalence of complementary medicine use in the past 12 months as well as prevalence of cancer screening uptake in the past 12 months were calculated. Results: At least one complementary medicine approach was used by 32.4% of participants. Controlling for sociodemographic and clinical variables, individuals who consulted a chiropractor or naturopath or who used mind-body medicine approaches were more likely to take up Pap smear test (odds ratio = 1.20-1.35), mammography (odds ratio = 1.22-1.38), and/or colorectal cancer screening (odds ratio = 1.18-1.37). Those consulting a homeopath were more likely to take up Pap smear test (odds ratio = 1.33). No association was found between consultations of practitioners of chelation therapy or traditional medicine and cancer screening uptake. Conclusion: Complementary medicine use seems to be associated with a better adherence to cancer screening. Individuals who consulted a chiropractor or naturopath or who used mind-body medicine approaches were more likely to take up the recommended screening

Craniosacral therapy for chronic pain: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES:To systematically assess the evidence of Craniosacral Therapy (CST) for the treatment of chronic pain. METHODS:PubMed, Central, Scopus, PsycInfo and Cinahl were searched up to August 2018. Randomized controlled trials (RCTs) assessing the effects of CST in chronic pain patients were eligible. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for pain intensity and functional disability (primary outcomes) using Hedges' correction for small samples. Secondary outcomes included physical/mental quality of life, global improvement, and safety. Risk of bias was assessed using the Cochrane tool. RESULTS:Ten RCTs of 681 patients with neck and back pain, migraine, headache, fibromyalgia, epicondylitis, and pelvic girdle pain were included. CST showed greater post intervention effects on: pain intensity (SMD = -0.32, 95%CI = [- 0.61,-0.02]) and disability (SMD = -0.58, 95%CI = [- 0.92,-0.24]) compared to treatment as usual; on pain intensity (SMD = -0.63, 95%CI = [- 0.90,-0.37]) and disability (SMD = -0.54, 95%CI = [- 0.81,-0.28]) compared to manual/non-manual sham; and on pain intensity (SMD = -0.53, 95%CI = [- 0.89,-0.16]) and disability (SMD = -0.58, 95%CI = [- 0.95,-0.21]) compared to active manual treatments. At six months, CST showed greater effects on pain intensity (SMD = -0.59, 95%CI = [- 0.99,-0.19]) and disability (SMD = -0.53, 95%CI = [- 0.87,-0.19]) versus sham. Secondary outcomes were all significantly more improved in CST patients than in other groups, except for six-month mental quality of life versus sham. Sensitivity analyses revealed robust effects of CST against most risk of bias domains. Five of the 10 RCTs reported safety data. No serious adverse events occurred. Minor adverse events were equally distributed between the groups. DISCUSSION:In patients with chronic pain, this meta-analysis suggests significant and robust effects of CST on pain and function lasting up to six months. More RCTs strictly following CONSORT are needed to further corroborate the effects and safety of CST on chronic pain. PROTOCOL REGISTRATION AT PROSPERO:CRD42018111975

Yoga for posttraumatic stress disorder - a systematic review and meta-analysis

© 2018 The Author(s). Background: Yoga is increasingly used as a therapeutic treatment and seems to improve psychiatric conditions such as anxiety disorders and depression. The aim of this systematic review was to assess the evidence of yoga for reducing symptoms of posttraumatic stress disorder (PTSD). Methods: The Cochrane Library, Medline/PubMed, PsycINFO, Scopus, and IndMED were searched through July 2017 for randomized controlled trials (RCTs) assessing the effects of yoga on symptoms of PTSD. Mean differences (MD) and standardized mean differences (SMD) with 95% confidence intervals (CI) were computed. The quality of evidence and the strength of recommendation were graded according to the GRADE recommendations. Results: Seven RCTs (N = 284) were included. Meta-analysis revealed low quality evidence for clinically relevant effects of yoga on PTSD symptoms compared to no treatment (SMD = - 1.10, 95% CI [- 1.72, - 0.47], p < .001, I2 = 72%; MD = - 13.11, 95% CI [- 17.95, - 8.27]); and very low evidence for comparable effects of yoga and attention control interventions (SMD = - 0.31, 95%CI = [- 0.84, 0.22], p = .25; I2 = 43%). Very low evidence was found for comparable retention of patients in the trial for yoga and no treatment (OR = 0.68, 95%CI [0.06, 7.72]) or attention control interventions (OR = 0.66, 95%CI [0.10, 4.46]). No serious adverse events were reported. Limitations: Few RCTs with only limited sample size were available. Conclusions: Only a weak recommendation for yoga as an adjunctive intervention for PTSD can be made. More high quality research is needed to confirm or disconfirm these findings

Associated factors and consequences of risk of bias in randomized controlled trials of yoga: A systematic review

© 2015 Cramer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Bias in randomized controlled trials (RCTs) of complementary therapy interventions seems to be associated with specific factors and to potentially distort the studies' conclusions. This systematic review assessed associated factors of risk of bias and consequences for the studies' conclusions in RCTs of yoga as one of the most commonly used complementary therapies. Methods: Medline/PubMed, Scopus, IndMED and the Cochrane Library were searched through February 2014 for yoga RCTs. Risk of selection bias was assessed using the Cochrane tool and regressed to a) publication year; b) country of origin; c) journal type; and d) impact factor using multiple logistic regression analysis. Likewise, the authors' conclusions were regressed to risk of bias. Results: A total of 312 RCTs were included. Impact factor ranged from 0.0 to 39.2 (median = 1.3); 60 RCT (19.2%) had a low risk of selection bias, and 252 (80.8%) had a high or unclear risk of selection bias. Only publication year and impact factor significantly predicted low risk of bias; RCTs published after 2001 (adjusted odds ratio (OR) = 12.6; 95% confidence interval (CI) = 1.7, 94.0; p<0.001) and those published in journals with impact factor (adjusted OR = 2.6; 95%CI = 1.4, 4.9; p = 0.004) were more likely to have low risk of bias. The authors' conclusions were not associated with risk of bias. Conclusions: Risk of selection bias was generally high in RCTs of yoga; although the situation has improved since the publication of the revised CONSORT statement 2001. Pre-CONSORT RCTs and those published in journals without impact factor should be handled with increased care; although risk of bias is unlikely to distort the RCTs' conclusions

Mindfulness-based stress reduction for breast cancer- A systematic review and meta-analysis

Objective The aim of this systematic review and meta-analysis was to assess the effectiveness of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) in patients with breast cancer. Methods The medline, Cochrane Library, embase, cambase, and PsycInfo databases were screened through November 2011. The search strategy combined keywords for MBSR and MBCT with keywords for breast cancer. Randomized controlled trials (RCTs) comparing MBSR or MBCT with control conditions in patients with breast cancer were included. Two authors independently used the Cochrane risk of bias tool to assess risk of bias in the selected studies. Study characteristics and outcomes were extracted by two authors independently. Primary outcome measures were health-related quality of life and psychological health. If at least two studies assessing an outcome were available, standardized mean differences (SMDS) and 95% confidence intervals (CIs) were calculated for that outcome. As a measure of heterogeneity, I 2 was calculated. Results Three RCTs with a total of 327 subjects were included. One RCT compared MBSR with usual care, one RCT compared MBSR with free-choice stress management, and a three-arm RCT compared MBSR with usual care and with nutrition education. Compared with usual care, MBSR was superior in decreasing depression (SMD: -0.37; 95% CI: -0.65 to -0.08; p = 0.01; I 2 = 0%) and anxiety (SMD: -0.51; 95% CI: -0.80 to -0.21; p = 0.0009; I 2 = 0%), but not in increasing spirituality (SMD: 0.27; 95% CI: -0.37 to 0.91; p = 0.41; I 2 = 79%). Conclusions There is some evidence for the effectiveness of MBSR in improving psychological health in breast cancer patients, but more RCTs are needed to underpin those results. © 2012 Multimed Inc