Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function.Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were “alcohol dependent” according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.
Objective To examine how poor reporting and inadequate methods for key methodological features in randomised controlled trials (RCTs) have changed over the past three decades.Design Mapping of trials included in Cochrane reviews.Data sources Data from RCTs included in all Cochrane reviews published between March 2011 and September 2014 reporting an evaluation of the Cochrane risk of bias items: sequence generation, allocation concealment, blinding, and incomplete outcome data.Data extraction For each RCT, we extracted consensus on risk of bias made by the review authors and identified the primary reference to extract publication year and journal. We matched journal names with Journal Citation Reports to get 2014 impact factors.Main outcomes measures We considered the proportions of trials rated by review authors at unclear and high risk of bias as surrogates for poor reporting and inadequate methods, respectively.Results We analysed 20 920 RCTs (from 2001 reviews) published in 3136 journals. The proportion of trials with unclear risk of bias was 48.7% for sequence generation and 57.5% for allocation concealment; the proportion of those with high risk of bias was 4.0% and 7.2%, respectively. For blinding and incomplete outcome data, 30.6% and 24.7% of trials were at unclear risk and 33.1% and 17.1% were at high risk, respectively. Higher journal impact factor was associated with a lower proportion of trials at unclear or high risk of bias. The proportion of trials at unclear risk of bias decreased over time, especially for sequence generation, which fell from 69.1% in 1986-1990 to 31.2% in 2011-14 and for allocation concealment (70.1% to 44.6%). After excluding trials at unclear risk of bias, use of inadequate methods also decreased over time: from 14.8% to 4.6% for sequence generation and from 32.7% to 11.6% for allocation concealment.Conclusions Poor reporting and inadequate methods have decreased over time, especially for sequence generation and allocation concealment. But more could be done, especially in lower impact factor journals.
This study investigates the association between eating out and depressive symptoms among elderly people. Potential mediators that may link to elderly eating out and depressive symptoms are also discussed.
Patients with essential thrombocythemia (ET) are at high risk for both thrombosis and hemorrhage.
The ability to generate heat under an alternating magnetic field (AMF) makes magnetic iron oxide nanoparticles (MIONs) an ideal heat source for biomedical applications including cancer thermoablative therapy, tissue preservation and remote control of cell function. However, there is a lack of quantitative understanding of the mechanisms governing heat generation of MIONs, and the optimal nanoparticle size for magnetic fluid heating (MFH) applications. Here we show that MIONs with large sizes (> 20nm) have significantly higher specific absorption rate (SAR) than that predicted by the widely used linear theory of MFH. The heating efficiency of MIONs in both the superparamagnetic and ferromagnetic regimes increased with size, which can be accurately characterized with a modified dynamic hysteresis model. In particular, the 40 nm ferromagnetic nanoparticles have an SAR value approaching the theoretical limit under a clinically relevant AMF. An in vivo study further demonstrated that the 40 nm MIONs could effectively heat tumor tissues at a minimal dose. Our experimental results and theoretical analysis on nanoparticle heating offer important insight into the rationale design of MION-based MFH for therapeutic applications.
Oligodendrocytes (OLGs) are the myelinating cells of the central nervous system (CNS), and its proper differentiation is crucial for normal functioning of neurons. Methyl-CpG-binding protein 2 (MeCP2) is a multifunctional methylated DNA binding protein; mutation of which causes Rett syndrome, a severe neurodevelopmental disorder. Previously, we reported that MeCP2 is expressed in all the stages of oligodendrocyte development, and also shown the role of MeCP2 as a transcription regulator of myelin genes in OLGs. The expression and function of MeCP2 phosphorylation at S80 (pS80MeCP2) has been well studied in neurons and astrocytes; however, there is no data so far available in OLGs regarding pS80MeCP2. Certain developmental stimuli such as growth factors and extracellular matrix (ECM) protein play important role in OLG development. In the present study, we have examined the effects of external stimuli (growth factors (GFs) and extracellular matrix (ECMs)) on S80 phosphorylation of MeCP2 in N19 oligodendroglial cells (N19 OLGs). This study provides the first evidence that laminin (LN) differentially regulates the expression of pS80MeCP2 in immature and mature N19 OLGs. Thus, MeCP2 is phosphorylated in a stimulus-dependent manner during oligodendrocyte development, and thereby, it may regulate the oligodendrocyte behavior.
Cadmium (Cd) contamination of soil and food crops is a ubiquitous environmental problem that has resulted from uncontrolled industrialization, unsustainable urbanization and intensive agricultural practices. Being a toxic element, Cd poses high threats to soil quality, food safety, and human health. Land is the ultimate source of waste disposal and utilization therefore, Cd released from different sources (natural and anthropogenic), eventually reaches soil, and then subsequently bio-accumulates in food crops. The stabilization of Cd in contaminated soil using organic amendments is an environmentally friendly and cost effective technique used for remediation of moderate to high contaminated soil. Globally, substantial amounts of organic waste are generated every day that can be used as a source of nutrients, and also as conditioners to improve soil quality. This review paper focuses on the sources, generation, and use of different organic amendments to remediate Cd contaminated soil, discusses their effects on soil physical and chemical properties, Cd bioavailability, plant uptake, and human health risk. Moreover, it also provides an update of the most relevant findings about the application of organic amendments to remediate Cd contaminated soil and associated mechanisms. Finally, future research needs and directions for the remediation of Cd contaminated soil using organic amendments are discussed.
A 10-month-old girl with type I Loeys-Dietz syndrome developed a conspicuous aortic root aneurysm that was well demonstrated on chest X-ray/CT reconstruction. She underwent successful valve-spare repair of the ascending aorta.
Objective: To systematically compare the differences in the detection rate of prostate cancer with fusion targeting biopsy and systemic biopsy. Methods: A computer-based search of PubMed, Medline, China Biomedical Literature Database and Wanfang database (from the beginning of establishment of library to October 2016) on the detection rate of prostate cancer by fusion targeting biopsy and systemic biopsy was performed manually.The inclusion and exclusion criteria were formulated by 2 reviewers, and the data were extracted and evaluated respectively. RevMan5.3 software was used to analyze the detection rate of prostate cancer by two biopsy methods. Results: A total of 15 related clinical studies were included, 5 337 cases were enrolled in the study, including 2 667 cases of targeted fusion biopsy and 2 670 cases of routine systemic biopsy. The results showed that the overall detection rate of prostate cancer in targeting fusion biopsy was significantly higher than that of conventional systemic biopsy (OR=1.16, 95% CI 1.04-1.30, P=0.007). The detection rates of prostate cancer with different risk grades by two biopsy methods were conducted. We found that targeted fusion biopsy had a significant advantage compared with conventional system biopsy (OR=1.37, 95% CI 1.19-1.58, P<0.05) in middle and high risk prostate cancer with Gleason ≥ 7 points. In low-risk prostate cancer patients with Gleason score <7, the detection rate of prostate cancer by targeted fusion biopsy was lower (OR=0.76, 95% CI 0.65-0.89, P<0.05) than that of conventional systemic biopsy. Conclusions: Targeted fusion biopsy was significantly better than systemic biopsy in the overall detection rate of prostate cancer and the detection rate of the middle and high risk prostate cancer with Gleason ≥7 points. However, systemic biopsy performed better in patients with Gleason<7 points of low-risk prostate cancer.
Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. Failure to reduce the dose in patients with severe kidney disease may increase bleeding risk, whereas dose reductions without a firm indication may decrease the effectiveness of stroke prevention.