CLCF1 inhibits energy expenditure via suppressing brown fat thermogenesis.

Brown adipose tissue (BAT) is the main site of nonshivering thermogenesis which plays an important role in thermogenesis and energy metabolism. However, the regulatory factors that inhibit BAT activity remain largely unknown. Here, cardiotrophin-like cytokine factor 1 (CLCF1) is identified as a negative regulator of thermogenesis in BAT. Adenovirus-mediated overexpression of CLCF1 in BAT greatly impairs the thermogenic capacity of BAT and reduces the metabolic rate. Consistently, BAT-specific ablation of CLCF1 enhances the BAT function and energy expenditure under both thermoneutral and cold conditions. Mechanistically, adenylate cyclase 3 (ADCY3) is identified as a downstream target of CLCF1 to mediate its role in regulating thermogenesis. Furthermore, CLCF1 is identified to negatively regulate the PERK-ATF4 signaling axis to modulate the transcriptional activity of ADCY3, which activates the PKA substrate phosphorylation. Moreover, CLCF1 deletion in BAT protects the mice against diet-induced obesity by promoting BAT activation and further attenuating impaired glucose and lipid metabolism. Therefore, our results reveal the essential role of CLCF1 in regulating BAT thermogenesis and suggest that inhibiting CLCF1 signaling might be a potential therapeutic strategy for improving obesity-related metabolic disorders.

Calorie Restriction with or without Time-Restricted Eating in Weight Loss.

BACKGROUND: The long-term efficacy and safety of time-restricted eating for weight loss are not clear. METHODS: We randomly assigned 139 patients with obesity to time-restricted eating (eating only between 8:00 a.m. and 4:00 p.m.) with calorie restriction or daily calorie restriction alone. For 12 months, all the participants were instructed to follow a calorie-restricted diet that consisted of 1500 to 1800 kcal per day for men and 1200 to 1500 kcal per day for women. The primary outcome was the difference between the two groups in the change from baseline in body weight; secondary outcomes included changes in waist circumference, body-mass index (BMI), amount of body fat, and measures of metabolic risk factors. RESULTS: Of the total 139 participants who underwent randomization, 118 (84.9%) completed the 12-month follow-up visit. The mean weight loss from baseline at 12 months was -8.0 kg (95% confidence interval [CI], -9.6 to -6.4) in the time-restriction group and -6.3 kg (95% CI, -7.8 to -4.7) in the daily-calorie-restriction group. Changes in weight were not significantly different in the two groups at the 12-month assessment (net difference, -1.8 kg; 95% CI, -4.0 to 0.4; P = 0.11). Results of analyses of waist circumferences, BMI, body fat, body lean mass, blood pressure, and metabolic risk factors were consistent with the results of the primary outcome. In addition, there were no substantial differences between the groups in the numbers of adverse events. CONCLUSIONS: Among patients with obesity, a regimen of time-restricted eating was not more beneficial with regard to reduction in body weight, body fat, or metabolic risk factors than daily calorie restriction. (Funded by the National Key Research and Development Project [No. 2018YFA0800404] and others; ClinicalTrials.gov number, NCT03745612.).

Pulsed rise and growth of the Tibetan Plateau to its northern margin since ca. 30 Ma.

The onset of mountain building along margins of the Tibetan Plateau provides a key constraint on the processes by which the high topography in Eurasia formed. Although progressive expansion of thickened crust underpins most models, several studies suggest that the northern extent of the plateau was established early, soon after the collision between India and Eurasia at ca. 50 Ma. This inference relies heavily on the age and provenance of Cenozoic sediments preserved in the Qaidam basin. Here, we present evidence in the northern plateau for a considerably younger inception and evolution of the Qaidam basin, based on magnetostratigraphies combined with detrital apatite fission-track ages that date the basin fills to be from ca. 30 to 4.8 Ma. Detrital zircon-provenance analyses coupled with paleocurrents reveal that two-stage growth of the Qilian Shan in the northeastern margin of the Tibetan Plateau began at ca. 30 and at 10 Ma, respectively. Evidence for ca. 30 and 10 to 15 Ma widespread synchronous deformation throughout the Tibetan Plateau and its margins suggests that these two stages of outward growth may have resulted from the removal of mantle lithosphere beneath different portions of the Tibetan Plateau.

Sex Hormone-Binding Globulin and Risk of Incident Dementia in Middle-Aged to Older Women: Results from the UK Biobank Cohort Study.

INTRODUCTION: The association of serum sex hormone-binding globulin (SHBG) concentrations with dementia risk remains uncertain in middle-aged to older women. We examined associations of serum SHBG levels with incidence of all-cause dementia and its subtypes in middle-aged to older women from the large population-based UK Biobank cohort study. METHODS: Serum total SHBG levels were measured by immunoassay. The incidence of all-cause dementia and its subtypes was recorded. Cox proportional hazards models were used to calculate hazard ratios (HR) for main outcomes. RESULTS: Among 171,482 community-dwelling women (mean [SD] age was 59.9 [5.4] years, median follow-up of 11.8 years), 2,368 developed dementia, including 1,088 from Alzheimer's disease (AD), 451 from vascular dementia (VAD), and 1,609 from other dementia. After multivariable adjustments, higher serum SHBG levels were significantly associated with higher risks of all-cause dementia, AD, and other dementia (all p < 0.05). Compared to those in the lowest quartile of SHBG levels, participants in the highest quartile of SHBG levels had a higher risk of all-cause dementia (HR: 1.34; 95% confidence interval [CI]: 1.16-1.53), AD (HR: 1.32; 95% CI: 1.07-1.62), and other dementia (HR: 1.44; 95% CI: 1.21-1.70). However, this relationship was not significant for VAD (HR: 1.16; 95% CI: 0.86-1.56). CONCLUSION: These findings indicated that higher serum SHBG concentrations were independently associated with higher risks of incident all-cause dementia, as well as AD and other dementia among middle-aged to older women. No association was found for VAD.

Effects of exercise interventions on quality of life in patients with breast cancer: A systematic review and network meta-analysis.

OBJECTIVE: To compare and rank the effectiveness of four primary categories of exercise modalities (aerobic, resistance, mind-body, and combined exercise [CE]) in improving the Quality of life (QoL) of women with breast cancer in a network meta-analysis (NMA). METHODS: Articles published in English and indexed in the PubMed (MEDLINE), EBSCO, Web of Science, SPORTDiscus, The Cochrane Library, Google Scholar, PsycINFO, EMBASE, and CINAHL Plus databases were identified from inception to 12 October 2023. Studies that met the eligibility criteria were assessed for risk of bias. A frequentist NMA was conducted to appraise the efficacy of different exercise types. RESULTS: This study included 56 studies with 3904 participants. Aerobic, mind-body, and combined exercises effectively improved QoL compared to controls. The surface under the cumulative ranking curve (SUCRA) indicated that CE best improved patients' QoL (SUCRA = 96.7%). Analysis of the secondary outcomes suggests that exercise reduced patients' depression (standardized mean difference [SMD] = -0.38, 95% confidence interval [CI] = -0.70 to -0.06, p < 0.001; I2 = 79%) and anxiety (SMD = -0.50, 95% CI = -0.69 to -0.31, p < 0.001; I2 = 27.4%) but did not affect self-esteem. CONCLUSION: All exercise types but resistance were effective in improving the QoL of women with breast cancer, CE (the combination of aerobic and resistance exercise) had the highest likelihood of being optimal for improving QoL.

Outcomes of pregnancies complicated by cirrhosis: a retrospective cohort study.

BACKGROUND: Although pregnancy complicated by liver cirrhosis is rare, women with cirrhosis experience increased adverse pregnancy outcomes. This study aimed to evaluate pregnancy outcomes in women with liver cirrhosis and develop a predictive model using maternal factors for preterm birth in such pregnancies. METHODS: A retrospective analysis was conducted on pregnancy outcomes of a cirrhosis group (n = 43) and a non-cirrhosis group (n = 172) in a university hospital between 2010 and 2022. Logistic regression evaluated pregnancy outcomes, and a forward stepwise logistic regression model was designed to predict preterm birth in pregnant women with cirrhosis. The model's predictive performance was evaluated using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). RESULTS: The incidence of cirrhosis during pregnancy was 0.06% (50/81,554). Pregnant women with cirrhosis faced increased risks of cesarean section, preterm birth, intrahepatic cholestasis of pregnancy, thrombocytopenia, and postpartum hemorrhage. In pregnant women with cirrhosis, preterm birth risk significantly increased at an incidence rate of 46.51% (20/43). According to the prediction model, the key predictors of preterm birth in pregnant women with cirrhosis were intrahepatic cholestasis of pregnancy and total bilirubin. The model demonstrated accurate prediction, with an AUC of 0.847, yielding a model accuracy of 81.4%. CONCLUSIONS: Pregnant women with cirrhosis face a heightened risk of adverse obstetric outcomes, particularly an increased incidence of preterm birth. The preliminary evidence shows that the regression model established in our study can use the identified key predictors to predict preterm birth in pregnant women with cirrhosis, with high accuracy.

Effects of exercise on depression and anxiety in postmenopausal women: a pairwise and network meta-analysis of randomized controlled trials.

BACKGROUND: Exercise has been identified as a promising non-pharmacological therapy for the management of depression, but there is still controversy over which type is most effective. We aimed to compare and rank the types of exercise that improve depression in postmenopausal women by quantifying information from randomized controlled trials (RCTs). METHODS: The PubMed, Web of Science, SPORTDiscus, CNKI, The Cochrane Library, PsycINFO, EMBASE, and CINAHL Plus databases were searched to identify articles published from inception to 1 March 2024 reporting RCTs that examined the effectiveness of exercise on depression in postmenopausal women. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for RCTs. The quality of the evidence for each comparison was graded using the online confidence in network meta-analysis tool (CINeMA). Standardized mean differences (SMDs) were calculated using the mean and standard deviation of pre-to-post intervention changes and then pooled using a random effects model in a pairwise meta-analysis using Review Manager 5.4. Then, a frequentist network meta-analysis was conducted using a random effects model was conducted to evaluate the efficacy of different exercise types using the network package of Stata 15. RESULTS: This study included 26 studies involving 2,170 participants. The pairwise meta-analysis revealed that exercise had a significant positive effect on depression in postmenopausal women (SMD = -0.71, 95% confidence interval [CI] = -0.94 to -0.48; I2 = 78%). The network meta-analysis revealed that mind-body exercise (SMD = -0.97, 95% CI = -1.28 to -0.67), aerobic exercise (SMD = -0.58, 95% CI = -0.88 to -0.27) and multicomponent exercise (SMD = -0.57, 95% CI = -1.15 to -0.002) significantly reduced depression compared to the control intervention. Mind-body exercise had the highest probability of being the most effective intervention. Exercise interventions also showed positive effects on anxiety. Most studies were judged to have some concerns regarding their risk of bias, and the confidence in evidence was often very low according to CINeMA. CONCLUSION: For postmenopausal women, there is very low to moderate quality evidence that exercise interventions are an effective antidepressant therapy, with mind-body exercise most likely being the optimal type. TRIAL REGISTRATION: This meta-analysis was prospectively registered with PROSPERO (registration number: CRD42024505425).

Debunking Mental Health Misperceptions in Short-Form Social Media Videos: An Experimental Test of Scientific Credibility Cues.

In recent years, short-form social media videos have emerged as an important source of health-related advice. In this study, we investigate whether experts or ordinary users in such videos are more effective in debunking the common misperception that talking about suicide should be avoided. We also explore a new trend on TikTok and other platforms, in which users attempt to back up their arguments by displaying scientific articles in the background of their videos. To test the effect of source type (expert vs. ordinary user) and scientific references (present or absent), we conducted a 2 × 2 between-subject plus control group experiment (n = 956). In each condition, participants were shown a TikTok video that was approximately 30 seconds long. Our findings show that in all four treatment groups, participants reduced their misperceptions on the topic. The expert was rated as being more authoritative on the topic compared to the ordinary user. However, the expert was also rated as being less credible compared to the ordinary user. The inclusion of a scientific reference did not make a difference. Thus, both experts and ordinary users may be similarly persuasive in a short-form video environment.

Role of exercise in reducing the risk of cardiovascular diseases associated with sleep disorders. / è¿åŠ¨é™ä½Žç¡çœ éšœç¢ç›¸å ³å¿ƒè¡€ç®¡ç–¾ç— é£Žé™©çš„ä½œç”¨.

Cardiovascular diseases are the leading cause of death among urban and rural residents and have become a major global public health problem. The prevention and control of cardiovascular disease risk factors is crucial for preventing, stabilizing, and even reversing cardiovascular disease. Studies have found that certain sleep disorders are directly related to cardiovascular disease and may be induced through pathways such as endothelial dysfunction, dysregulation of autonomic homeostasis, inflammatory response, and metabolic dysfunction. Exercise helps improve sleep disorders and thus reduce the risk of cardiovascular disease, and has irreplaceable advantages over pharmacological treatments for improving sleep. Different types of sleep disorders should be adjusted by factors such as exercise mode, intensity, and duration of exercise. A good sleep state further reduces the risk of cardiovascular disease. Discussing the effect of exercise on the improvement of the risk of cardiovascular disease associated with sleep disorders, and elaborating the mechanism of action of exercise in reducing the risk of cardiovascular disease from the perspective of sleep, can lay a foundation for the treatment of sleep disorders by exercise and propose new directions for reducing cardiovascular disease risk.

Exercise perspective: Benefits and mechanisms of gut microbiota on the body. / è¿åŠ¨è§’åº¦ï¼šè‚ é“èŒç¾¤å¯¹æœºä½“çš„ç›Šå¤„åŠå ¶æœºåˆ¶.

Gut microbiota refers to the vast and diverse community of microorganisms residing in the intestines. Factors such as genetics, environmental influences (e.g., exercise, diet), and early life experiences (e.g., infant feeding methods) can all affect the ecological balance of gut microbiota within the body. Dysbiosis of the gut microbiota is associated with extra-intestinal diseases such as Parkinson's syndrome, osteoporosis, and autoimmune diseases, suggesting that disturbances in gut microbiota may be one of the causes of these diseases. Exercise benefits various diseases, with gut microbiota playing a role in regulating the nervous, musculoskeletal, and immune systems. Gut microbiota can impact the body's health status through the gut-brain axis, gut-muscle axis, and immune pathways. Moderate-intensity aerobic exercise can increase the quantity of gut microbiota and change microbial abundance, although short-term exercise does not significantly affect the alpha diversity of the microbiota. Resistance exercise also does not have a significant regulatory effect on gut microbiota.

Regulation of exercise on heart rate variability in perimenopausal and postmenopausal women. / 运动对围绝经期和绝经后妇女心率变异性的调节.

Heart rate variability (HRV) is a non-invasive quantitative measure of cardiac autonomic nervous activity. Due to the increase of age and the decrease of estrogen level in perimenopausal and postmenopausal women, the cardiac autonomic nervous function is abnormal, increasing the risk of cardiovascular disease. Proper exercise can increase estrogen levels, improve cardiovascular health, regulate cardiac autonomic nervous activity, and reduce the risk of cardiovascular disease. Low-moderate intensity aerobic exercise, resistance exercise, aerobic combined resistance exercise and mind-body exercise have positive effects on HRV in perimenopausal and postmenopausal women. Therefore, summarizing the effects of different exercise modes on HRV in perimenopausal and postmenopausal women, as well as the mechanism of exercise training improvement on HRV, so as to adopt better exercise strategies to improve HRV of perimenopausal and postmenopausal women, and thus reduce the risk of cardiovascular diseases and improve the health level and quality of life of perimenopausal and postmenopausal women.

Leukemia inhibitory factor protects against liver steatosis in nonalcoholic fatty liver disease patients and obese mice.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. However, the molecular mechanisms that promote dysregulation of hepatic triglyceride metabolism and lead to NAFLD are poorly understood, and effective treatments are limited. Leukemia inhibitory factor (LIF) is a member of the interleukin-6 cytokine family and has been shown to regulate a variety of physiological processes, although its role in hepatic triglyceride metabolism remains unknown. In the present study, we measured circulating LIF levels by ELISA in 214 patients with biopsy-diagnosed NAFLD as well as 314 normal control patients. We further investigated the potential role and mechanism of LIF on hepatic lipid metabolism in obese mice. We found that circulating LIF levels correlated with the severity of liver steatosis. Patients with ballooning, fibrosis, lobular inflammation, and abnormally elevated liver injury markers alanine transaminase and aspartate aminotransferase also had higher levels of serum LIF than control patients. Furthermore, animal studies showed that white adipose tissue-derived LIF could ameliorate liver steatosis through activation of hepatic LIF receptor signaling pathways. Together, our results suggested that targeting LIF-LIF receptor signaling might be a promising strategy for treating NAFLD.

Exercise as the Key to Improve Cardiopulmonary Function in Patients with Valvular Heart Disease: A Systematic Review and Meta-Analysis.

Background: Valvular heart disease (VHD) is a type of cardiovascular disease with abnormal heart valve structure and/or function and a rapidly growing cause of global cardiovascular morbidity and mortality. Physical inactivity is a problem for patients with VHD, especially after surgery. However, there is no data on the effects of exercise on VHD from large multicentre randomised controlled trials (RCTs). Therefore, we conducted a systematic review and meta-analysis to provide a comprehensive analysis of small RCTs to evaluate the effects of exercise on cardiopulmonary function in patients with VHD and provide an evidence-based medicine basis for developing and guiding the clinical application of exercise in patients with VHD. Methods: We conducted a systematic review and meta-analysis of RCTs. We systematically searched electronic databases (PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure [CNKI], China Science and Technology Journal Database [VIP], WanFang Database, and SinoMed [CBM]) for all studies on exercise and VHD from their inception to January 2023. The quality of included studies was assessed using the Cochrane risk-of-bias tool. The primary outcomes were the six-minute walk test distance (6MWD), left ventricular ejection fraction (LVEF), and short-form 36-item health survey (SF-36). Results: This systematic review included 22 RCTs with 1520 subjects (869 men and 651 women). The meta-analysis results showed that exercise significantly improved exercise capacity measured by the 6MWD (mean difference [MD] = 25.54, 95% confidence interval [CI] = 19.98-31.11, I 2 = 0%, p < 0.00001), LVEF (MD = 6.20, 95% CI = 4.76-7.65, I 2 = 66%, p < 0.00001), and quality of life measured by the SF-36 (physical function: MD = 3.42, 95% CI = 2.12-4.72, I 2 = 12%, p < 0.00001; mental health: MD = 3.86, 95% CI = 0.52-7.20, I 2 = 68%, p = 0.020; social function: MD = 2.30, 95% CI = 0.64-3.97, I 2 = 45%, p = 0.007; bodily pain: MD = 2.60, 95% CI = 0.83-4.37, I 2 = 22%, p = 0.004) in patients with VHD compared to healthy controls. Conclusions: This study suggests that exercise can significantly improve cardiopulmonary function, enhance physical and social function, reduce bodily pain, and potentially improve mental health in patients with VHD, providing an evidence-based basis for better recovery in patients with VHD.

Circulating galectin-3 levels are inversely associated with subclinical cardiovascular disease in obese adults.

BACKGROUND: Galectin-3 is a new cytokine that is mainly secreted by activated macrophages. It is involved in apoptosis, inflammation and may play a role in the development of cardiovascular disease (CVD). However, there is little information about the association between circulating galectin-3 and subclinical atherosclerosis in humans. METHODS AND RESULTS: We measured serum galectin-3 in 483 obese adult subjects (aged 40 years and over) who had the measurement of carotid intima-media thickness (CIMT) recruited from the community. Adults with lower levels of circulating galectin-3 had increased CIMT (p < 0.05). In multivariable linear regression analyses, circulating galectin-3 was independently associated with CIMT. The risks of increased CIMT were significantly decreased by 65.1% (OR (95% CI): 0.349 (0.165-0.739)), adjusting for possible confounding factors. Notably, individuals in the lowest quartile of serum galectin-3 were 1.80 times (p < 0.05) more likely to have increased CIMT than those in the highest quartile in multivariable logistic regression analyses; however, such associations with circulating galectin-3 were not noted for carotid plague. CONCLUSIONS: These findings propose that circulating galectin-3 concentrations are inversely associated with increased CIMT in obese adults, which may be a potential biomarker of CVD.

Direction of Arrival Estimation and Highlighting Characteristics of Testing Wideband Echoes from Multiple Autonomous Underwater Vehicles.

Multiple autonomous underwater vehicles (AUVs) have gradually become the trend in underwater operations. Identifying and detecting these new underwater multi-targets is difficult when studying underwater moving targets. A 28-element transducer is used to test the echo of multiple AUVs with different layouts in a lake. The characteristics of the wideband echo signals are studied. Under the condition that the direction of arrival (DOA) is not known, an autofocus coherent signal subspace (ACCSM) method is proposed. The focusing matrix is constructed based on the received data. The spatial spectrum of the array signal of multiple AUVs at different attitudes is calculated. The algorithm estimates the DOA of the echo signals to overcome the shortcomings of traditional wideband DOA estimation and improve its accuracy. The results show that the highlights are not only related to the number of AUVs, but are also modified by scale and attitude. The contribution of the microstructure of the target in the overall echo cannot be ignored. Different parts of the target affect the number of highlights, thus resulting in varying numbers of highlights at different attitude angle intervals. The results have significant implications for underwater multi-target recognition.

Association of circulating adipsin with nonalcoholic fatty liver disease in obese adults: a cross-sectional study.

BACKGROUND: As a secreted adipokine, adipsin has been recently shown to play a pivotal role in metabolic disorders. However, information regarding the association of circulating adipsin with non-alcoholic fatty liver disease (NAFLD) in humans is scant. METHODS: We recruited 1163 obese adult subjects with waist circumference at least 90 cm in men and 80 cm in women from the community. Circulating adipsin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Circulating adipsin levels of NAFLD subjects was decreased compared to those in non-NAFLD (p < 0.05). The prevalence of NAFLD with lower levels of serum adipsin was significantly higher than those with higher values (57.6% vs. 50.9%, p < 0.05). Circulating adipsin levels were significantly associated with decreasing levels of fasting glucose and postprandial glucose (both p < 0.001 for interaction) in NAFLD subjects but not in non-NAFLD subjects. The risk of NAFLD was significantly decreased by 21.7% [OR (95% CI): 0.783 (0.679-0.902), p < 0.001], adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, HOMA-IR, and body fat mass. Importantly, subjects in the lowest quartile of circulating adipsin were 1.88 times more likely to have NAFLD than those in the highest quartile in multivariable logistic regression analyses. However, such associations with circulating adipsin were not noted for metabolic syndrome, abnormal liver enzyme and significant liver fibrosis. CONCLUSIONS: These results demonstrate that circulating adipsin levels in Chinese obese adults are negatively associated with risk of NAFLD, implying that serum adipsin levels may be a potential protective factor in NAFLD.

Human chorionic gonadotropin improves endometriosis through downregulation of leptin expression in rats.

OBJECTIVE: To investigate whether and how human chorionic gonadotropin (HCG) treatment ameliorates endometriosis in an endometriotic rat model. METHODS: Twenty-four endometriosis rats were established and were randomly divided into four groups, and then the rats were treated with 19.4, 25.8, and 51.6 IU/100 g weight/day of HCG, respectively. The control group was treated with 0.9% NaCl. After 15 days (3 estrous cycles), the ectopic lesion volume and the expression of leptin protein in eutopic and ectopic endometrium were investigated. RESULTS: After HCG treatment, the volumes of endometriotic lesions were significantly smaller than those before treatment. During endometriosis development, the expression of leptin protein in eutopic and ectopic endometrium was remarkably increased. HCG administration reversed leptin upregulation in endometriotic tissues. CONCLUSION: HCG therapy appears to be an effective treatment for endometriosis in rats through down-regulation of leptin expression in eutopic and ectopic endometrium.

Two-week normobaric intermittent hypoxia exposures enhance oxyhemoglobin equilibrium and cardiac responses during hypoxemia.

Intermittent hypoxia (IH) is extensively applied to challenge cardiovascular and respiratory function, and to induce physiological acclimatization. The purpose of this study was to test the hypothesis that oxyhemoglobin equilibrium and tachycardiac responses during hypoxemia were enhanced after 14-day IH exposures. Normobaric-poikilocapnic hypoxia was induced with inhalation of 10% O2 for 5-6 min interspersed with 4 min recovery on eight nonsmokers. Heart rate (HR), arterial O2 saturation (SaO 2), and end-tidal O2 (PetO 2) were continuously monitored during cyclic normoxia and hypoxia. These variables were compared during the first and fifth hypoxic bouts between day 1 and day 14. There was a rightward shift in the oxyhemoglobin equilibrium response following 14-day IH exposures, as indicated by the greater PetO 2 (an index of arterial Po2) at 50% of SaO 2 on day 14 compared with day 1 [33.9 ± 1.5 vs. 28.2 ± 1.3 mmHg (P = 0.005) during the first hypoxic bout and 39.4 ± 2.4 vs. 31.4 ± 1.5 mmHg (P = 0.006) during the fifth hypoxic bout] and by the augmented gains of ΔSaO 2/ΔPetO 2 (i.e., deoxygenation) during PetO 2 from 65 to 40 mmHg in the first (1.12 ± 0.08 vs. 0.80 ± 0.02%/mmHg, P = 0.001) and the fifth (1.76 ± 0.31 vs. 1.05 ± 0.06%/mmHg, P = 0.024) hypoxic bouts. Repetitive IH exposures attenuated (P = 0.049) the tachycardiac response to hypoxia while significantly enhancing normoxic R-R interval variability in low-frequency and high-frequency spectra without changes in arterial blood pressure at rest or during hypoxia. We conclude that 14-day IH exposures enhance arterial O2 delivery and improve vagal control of HR during hypoxic hypoxemia.

Placental methylation markers in normal and trisomy 21 tissues.

OBJECTIVE: The objective of this study is to combine multiplex ligation-dependent probe amplification (MLPA) and bisulfite sequencing to determine DNA methylation markers for noninvasive prenatal diagnosis of Down syndrome. METHODS: DNA methylation ratios (MR) of four fragments (CGI149, CGI045, HLCS-1, and HLCS-2) on chromosome 21 were evaluated in blood cells from 13 nonpregnant women, 15 euploidies, and 11 Down Syndrome (DS) placentae. Ratios were measured by bisulfite sequencing and methylation-specific (MS)-MLPA. RESULTS: The MS-MLPA and bisulfite sequencing results were concordant. CGI149, CGI045, and HLCS-2 were unmethylated in all nonpregnant blood cells. CGI149, CGI045, HLCS-1, and HLCS-2 were methylated in most of the euploid (13, 11, 15, and 15, respectively) and DS placentae (10, 11, 11, and 11, respectively). The median placental DNA MR in CGI149 was 0.4578 (interquartile range, 0.3568-0.5169) and 0.5918 (interquartile range, 0.5618-0.6659) in euploid and DS placentae, respectively (p = 0.001). Using placental MR at 0.5390 as a threshold, we detected DS at 90.9% sensitivity and 93.3% specificity. CONCLUSION: The MS-MLPA is an effective alternative to bisulfite sequencing in assessing placental MR. CGI149 is a potential marker for the noninvasive diagnosis of Down syndrome.

Statins for primary prevention of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is common in clinical practice. The efficacy of statins in the primary prevention of VTE remains unproven. This is an update of the review first published in 2011. OBJECTIVES: To assess the efficacy of statins in the primary prevention of VTE. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases (PVD) Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and CENTRAL (2014, Issue 1). SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed statins in the primary prevention of VTE were considered. The outcomes we evaluated were the rates of VTE, cardiovascular and cerebrovascular events, death and adverse events. Two authors (L Li, JH Tian) independently selected RCTs against the inclusion criteria. Disagreements were resolved by discussion with a third author (KH Yang). DATA COLLECTION AND ANALYSIS: Data extraction was independently carried out by two authors (L Li, JH Tian). Disagreements were resolved by discussion with a third author (PZ Zhang). Two authors (L Li, JH Tian) independently assessed the risk of bias according to a standard quality checklist provided by the PVD Group. MAIN RESULTS: For this update we included one RCT with 17,802 participants that assessed rosuvastatin compared with placebo for the prevention of VTE. The quality of the evidence was moderate because of imprecision, as the required sample size for the outcomes of this review was not achieved. Analysis showed that when compared with placebo rosuvastatin reduced the incidence of VTE (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.37 to 0.86) and deep vein thrombosis (DVT) (OR 0.45, 95% CI 0.25 to 0.79), the risk of any (fatal and non-fatal) myocardial infarction (MI) (OR 0.45, 95% CI 0.30 to 0.69), and any (fatal and non-fatal) stroke (OR 0.51, 95% CI 0.34 to 0.78). There was no difference in the incidence of pulmonary embolism (PE) (OR 0.77, 95% CI 0.41 to 1.46), fatal MI (OR 1.50, 95% CI 0.53 to 4.22), fatal stroke (OR 0.30, 95% CI 0.08 to 1.09) or death after VTE (OR 0.50, 95% CI 0.20 to 1.24). The incidence of any serious adverse events was no different between the rosuvastatin and placebo groups (OR 1.07, 95% CI 0.95 to 1.20). AUTHORS' CONCLUSIONS: Available evidence showed that rosuvastatin was associated with a reduced incidence of VTE, but the evidence was limited to a single RCT and any firm conclusions and suggestions could be not drawn. Randomised controlled trials of statins (including rosuvastatin) are needed to evaluate their efficacy in the prevention of VTE.