Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

<b>Background</b> Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. <p></p> <b>Methods</b> 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. <p></p> <b>Results</b> People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. <p></p> <b>Conclusion</b> People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

Archaeological Support for the Three-Stage Expansion of Modern Humans across Northeastern Eurasia and into the Americas

Background Understanding the dynamics of the human range expansion across northeastern Eurasia during the late Pleistocene is central to establishing empirical temporal constraints on the colonization of the Americas [1]. Opinions vary widely on how and when the Americas were colonized, with advocates supporting either a pre-[2] or post-[1], [3], [4], [5], [6] last glacial maximum (LGM) colonization, via either a land bridge across Beringia [3], [4], [5], a sea-faring Pacific Rim coastal route [1], [3], a trans-Arctic route [4], or a trans-Atlantic oceanic route [5]. Here we analyze a large sample of radiocarbon dates from the northeast Eurasian Upper Paleolithic to identify the origin of this expansion, and estimate the velocity of colonization wave as it moved across northern Eurasia and into the Americas. Methodology/Principal Findings We use diffusion models [6], [7] to quantify these dynamics. Our results show the expansion originated in the Altai region of southern Siberia ~46kBP , and from there expanded across northern Eurasia at an average velocity of 0.16 km per year. However, the movement of the colonizing wave was not continuous but underwent three distinct phases: 1) an initial expansion from 47-32k calBP; 2) a hiatus from ~32-16k calBP, and 3) a second expansion after the LGM ~16k calBP. These results provide archaeological support for the recently proposed three-stage model of the colonization of the Americas [8], [9]. Our results falsify the hypothesis of a pre-LGM terrestrial colonization of the Americas and we discuss the importance of these empirical results in the light of alternative models. Conclusions/Significance Our results demonstrate that the radiocarbon record of Upper Paleolithic northeastern Eurasia supports a post-LGM terrestrial colonization of the Americas falsifying the proposed pre-LGM terrestrial colonization of the Americas. We show that this expansion was not a simple process, but proceeded in three phases, consistent with genetic data, largely in response to the variable climatic conditions of late Pleistocene northeast Eurasia. Further, the constraints imposed by the spatiotemporal gradient in the empirical radiocarbon record across this entire region suggests that North America cannot have been colonized much before the existing Clovis radiocarbon record suggests

Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease:Systematic review and meta-analysis

Complete search strategy. The complete search strategy for the systematic review for both Medline and Embase. (DOCX 22 kb

A Comparison of Stress Levels, Coping Styles and Psychological Morbidity Between Graduate-entry and Traditional Undergraduate Medical Students During the First 2 Years at a UK Medical School.

Background: Stress levels and psychological morbidity are high among undergraduate medical students (UGs), but there is a lack of research into the psychological health of UK graduate-entry medical students (GEs). GEs are likely to experience different (perhaps more severe) stressors and to cope with stress differently. We compared stress levels, psychological morbidity and coping styles in GE versus UG medical students studying at the same UK medical school in the same academic year. Method: A cross-sectional self-rated questionnaire study of all first- and second-year GE and UG medical students. Perceived stress, psychological morbidity, recent adverse life events, stress-related personality traits and coping styles were assessed using standard questionnaires. Results: 75% GEs and 46% UGs responded to the questionnaire. Both groups reported equally high levels, and similar profiles of, perceived stress and psychological morbidity. Levels of recent adverse life events and stress-related personality traits were similar in both groups. Compared to UGs, GEs were more likely to use active coping (p = 0.02) and positive reframing (p = 0.03), but were also more likely to use substances (alcohol and other drugs; p < 0.001) to help them cope. Unlike UGs, second-year GEs showed less perceived stress (p = 0.007) and psychological morbidity (p = 0.006) than first-year GEs although levels of both were still high. Conclusion: Our results show that both GE students and their younger UG counterparts on a traditional medical course have similar profiles of stress symptoms. They do, however, cope with stress differently. GEs are more likely to use active problem-focused coping strategies, and they are also more likely to cope by using substances (alcohol or other drugs). GE students need interventions to prevent maladaptive coping styles and encourage adaptive coping that are tailored to their needs. Such interventions should be targeted at first-year students. It is vital that these students develop positive coping skills to benefit them during training and in a future career that is inherently stressful

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Regulation of Apoptotic Effects by Erythrocarpine E, a Cytotoxic Limonoid from Chisocheton erythrocarpus in HSC-4 Human Oral Cancer Cells

The aim of this study was to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a limonoid extracted from Chisocheton erythrocarpus on human oral squamous cell carcinoma. Based on preliminary dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, CEB4 treated HSC-4 cells demonstrated a cytotoxic effect and inhibited cell proliferation in a time and dose dependent manner with an IC50 value of 4.0±1.9 µM within 24 h of treatment. CEB4 was also found to have minimal cytotoxic effects on the normal cell line, NHBE with cell viability levels maintained above 80% upon treatment. Annexin V-fluorescein isothiocyanate (FITC), poly-ADP ribose polymerase (PARP) cleavage and DNA fragmentation assay results showed that CEB4 induces apoptosis mediated cell death. Western blotting results demonstrated that the induction of apoptosis by CEB4 appeared to be mediated through regulation of the p53 signalling pathway as there was an increase in p53 phosphorylation levels. CEB4 was also found to up-regulate the pro-apoptotic protein, Bax, while down-regulating the anti-apoptotic protein, Bcl-2, suggesting the involvement of the intrinsic mitochondrial pathway. Reduced levels of initiator procaspase-9 and executioner caspase-3 zymogen were also observed following CEB4 exposure, hence indicating the involvement of cytochrome c mediated apoptosis. These results demonstrate the cytotoxic and apoptotic ability of erythrocarpine E, and suggest its potential development as a cancer chemopreventive agent

Updated Three-Stage Model for the Peopling of the Americas

Background: We re-assess support for our three stage model for the peopling of the Americas in light of a recent report that identified nine non-Native American mitochondrial genome sequences that should not have been included in our initial analysis. Removal of these sequences results in the elimination of an early (i.e.,40,000 years ago) expansion signal we had proposed for the proto-Amerind population. Methodology/Findings: Bayesian skyline plot analysis of a new dataset of Native American mitochondrial coding genomes confirms the absence of an early expansion signal for the proto-Amerind population and allows us to reduce the variation around our estimate of the New World founder population size. In addition, genetic variants that define New World founder haplogroups are used to estimate the amount of time required between divergence of proto-Amerinds from the Asian gene pool and expansion into the New World. Conclusions/Significance: The period of population isolation required for the generation of New World mitochondrial founder haplogroup-defining genetic variants makes the existence of three stages of colonization a logical conclusion. Thus, our three stage model remains an important and useful working hypothesis for researchers interested in the peopling of th

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Epistasis and genotype-by-environment interaction of grain protein content in durum wheat

Parental, F1 , F 2 , BC 1 and BC 2 generations of four crosses involving four cultivars of durum wheat (Triticum durum Desf.) were evaluated at two sites in Tunisia. A three-parameter model was found inadequate for all cases except crosses Chili x Cocorit 71 at site Sidi Thabet and Inrat 69 x Karim at both sites. In most cases a digenic epistatic model was sufficient to explain variation in generation means. Dominance effects (h) and additive x additive epistasis (i) (when significant) were more important than additive (d) effects and other epistatic components. Considering the genotype-by-environment interaction, the non-interactive model (m, d, h, e) was found adequate. Additive variance was higher than environmental variance in three crosses at both sites. The estimated values of narrow-sense heritability were dependent upon the cross and the sites and were 0%-85%. The results indicate that appropriate choice of environment and selection in later generations would increase grain protein content in durum wheat