Cardiovascular risk factors in secondary progressive multiple sclerosis: A cross-sectional analysis from the MS-STAT2 randomized controlled trial.

BACKGROUND AND PURPOSE: There is increasing evidence that cardiovascular risk (CVR) contributes to disability progression in multiple sclerosis (MS). CVR is particularly prevalent in secondary progressive MS (SPMS) and can be quantified through validated composite CVR scores. The aim was to examine the cross-sectional relationships between excess modifiable CVR, whole and regional brain atrophy on magnetic resonance imaging, and disability in patients with SPMS. METHODS: Participants had SPMS, and data were collected at enrolment into the MS-STAT2 trial. Composite CVR scores were calculated using the QRISK3 software. Prematurely achieved CVR due to modifiable risk factors was expressed as QRISK3 premature CVR, derived through reference to the normative QRISK3 dataset and expressed in years. Associations were determined with multiple linear regressions. RESULTS: For the 218 participants, mean age was 54 years and median Expanded Disability Status Scale was 6.0. Each additional year of prematurely achieved CVR was associated with a 2.7 mL (beta coefficient; 95% confidence interval 0.8-4.7; p = 0.006) smaller normalized whole brain volume. The strongest relationship was seen for the cortical grey matter (beta coefficient 1.6 mL per year; 95% confidence interval 0.5-2.7; p = 0.003), and associations were also found with poorer verbal working memory performance. Body mass index demonstrated the strongest relationships with normalized brain volumes, whilst serum lipid ratios demonstrated strong relationships with verbal and visuospatial working memory performance. CONCLUSIONS: Prematurely achieved CVR is associated with lower normalized brain volumes in SPMS. Future longitudinal analyses of this clinical trial dataset will be important to determine whether CVR predicts future disease worsening.

Vitamin A deficiency and determinants of vitamin A status in Bangladeshi children and women: findings of a national survey.

OBJECTIVE: Using data from the national micronutrients survey 2011-2012, the present study explored the status of subclinical vitamin A nutrition and the underlying determinants in the Bangladeshi population. DESIGN: A nationwide cross-sectional study. Settings The survey covered 150 clusters; fifty in each of rural, urban and slum strata. SUBJECTS: Three population groups: (i) pre-school age children (6-59 months; PSAC); (ii) school age children (6-14 years; SAC); and (iii) non-pregnant non-lactating women (15-49 years; NPNLW). RESULTS: National prevalence of subclinical vitamin A deficiency was 20·5, 20·8 and 5·3 % in PSAC, SAC and NPNLW, respectively. Slum populations had higher prevalence compared with urban (PSAC: 38·1 v. 21·2 %, P0·05 for differences in ß between <3 months v. 3-6 months, 6-9 months and 9-12 months). CONCLUSIONS: Prevalence of subclinical vitamin A deficiency was high in children in Bangladesh. Intakes of animal-source foods and leafy vegetables were associated with higher and lower retinol status, respectively. Increased food diversity through animal-source foods is required.

Determinants of iron status and Hb in the Bangladesh population: the role of groundwater iron.

OBJECTIVE: Using data from the national micronutrients survey 2011-2012, the present study explored the determinants of Fe status and Hb levels in Bangladesh with a particular focus on groundwater Fe. DESIGN: Cross-sectional study conducted at the nationwide scale. Settings The survey was conducted in 150 clusters, fifty in each of the three strata of rural, urban and slum. SUBJECTS: Three population groups: pre-school age children (6-59 months; PSAC), school age children (6-14 years; SAC) and non-pregnant non-lactating women (15-49 years; NPNLW). RESULTS: National prevalence of Fe deficiency was 10·7 %, 7·1 % and 3·9-9·5 % in PSAC, NPNLW and SAC, respectively. Prevalence of anaemia was 33·1 % (PSAC), 26·0 % (NPNLW) and 17·1-19·1 % (SAC). Multivariate regression analyses showed that the area with 'predominantly high groundwater Fe' was a determinant of higher serum ferritin levels in NPNLW (standardized ß=0·19; P=0·03), SAC (standardized ß=0·22; P=0·01) and PSAC (standardized ß=0·20; P=0·03). This area also determined higher levels of Hb in PSAC (standardized ß=0·14; P=0·01). CONCLUSIONS: National prevalence of Fe deficiency in Bangladesh is low, contrary to the widely held assumption. High Fe level in groundwater is associated with higher Fe status (all populations) and higher Hb level (PSAC).

A Systematic Review of the Benefits of Physical Exercise on Mental Health and Quality of Life in Patients With Substance Use Disorders.

Physical exercise is increasingly recognized for its potential therapeutic effects in individuals with substance use disorders (SUDs), particularly in terms of relapse prevention, mental health improvement, and enhanced quality of life (QoL). This systematic review aimed to statistically summarize findings from numerous randomized controlled trials (RCTs) on the effects of physical exercise on mental health outcomes, QoL, abstinence-related outcomes, and cravings among SUD patients. A systematic search was conducted across PubMed, Web of Science, and Scopus databases, resulting in the inclusion of 15 studies, comprising RCTs, cohort studies, observational studies, and quasi-experimental designs. The review revealed a significant reduction in stress and depression, with a standardized mean difference (SMD) of 0.63, indicating a moderate effect size. Patients engaging in physical exercise reported a higher QoL across various domains, although the trend toward reduced cravings was not statistically significant, suggesting a need for further research in this area. The findings suggest that physical exercise can positively contribute to the treatment of SUD patients by enhancing mental health and QoL.

Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial.

Background: Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by changes in the local magnetic field. In the deep grey matter, susceptibility has previously been validated against tissue iron concentration. However, it currently remains unknown whether susceptibility is abnormal in older progressive MS cohorts, and whether it correlates with disability. Objectives: To investigate differences in mean regional susceptibility in deep grey matter between people with secondary progressive multiple sclerosis (SPMS) and healthy controls; to examine in patients the relationships between deep grey matter susceptibility and clinical and imaging measures of disease severity. Methods: Baseline data from a subgroup of the MS-STAT2 trial (simvastatin vs. placebo in SPMS, NCT03387670) were included. The subgroup underwent clinical assessments and an advanced MRI protocol at 3T. A cohort of age-matched healthy controls underwent the same MRI protocol. Susceptibility maps were reconstructed using a robust QSM pipeline from multi-echo 3D gradient-echo sequence. Regions of interest (ROIs) in the thalamus, globus pallidus and putamen were segmented from 3D T1-weighted images, and lesions segmented from 3D fluid-attenuated inversion recovery images. Linear regression was used to compare susceptibility from ROIs between patients and controls, adjusting for age and sex. Where significant differences were found, we further examined the associations between ROI susceptibility and clinical and imaging measures of MS severity. Results: 149 SPMS (77% female; mean age: 53 yrs; median Expanded Disability Status Scale (EDSS): 6.0 [interquartile range 4.5-6.0]) and 33 controls (52% female, mean age: 57) were included.Thalamic susceptibility was significantly lower in SPMS compared to controls: mean (SD) 28.6 (12.8) parts per billion (ppb) in SPMS vs. 39.2 (12.7) ppb in controls; regression coefficient: -12.0 [95% confidence interval: -17.0 to -7.1], p < 0.001. In contrast, globus pallidus and putamen susceptibility were similar between both groups.In SPMS, a 10 ppb lower thalamic susceptibility was associated with a +0.13 [+0.01 to +0.24] point higher EDSS (p < 0.05), a -2.4 [-3.8 to -1.0] point lower symbol digit modality test (SDMT, p = 0.001), and a -2.4 [-3.7 to -1.1] point lower Sloan low contrast acuity, 2.5% (p < 0.01).Lower thalamic susceptibility was also strongly associated with a higher T2 lesion volume (T2LV, p < 0.001) and lower normalised whole brain, deep grey matter and thalamic volumes (all p < 0.001). Conclusions: The reduced thalamic susceptibility found in SPMS compared to controls suggests that thalamic iron concentrations are lower at this advanced stage of the disease. The observed relationships between lower thalamic susceptibility and more severe physical, cognitive and visual disability suggests that reductions in thalamic iron may correlate with important mechanisms of clinical disease progression. Such mechanisms appear to intimately link reductions in thalamic iron with higher T2LV and the development of thalamic atrophy, encouraging further research into QSM-derived thalamic susceptibility as a biomarker of disease severity in SPMS.

A comparative 'omics' approach for prediction of candidate Strongyloides stercoralis diagnostic coproantigens.

Human infection with the intestinal nematode Strongyloides stercoralis is persistent unless effectively treated, and potentially fatal in immunosuppressed individuals. Epidemiological data are lacking, partially due to inadequate diagnosis. A rapid antigen detection test is a priority for population surveillance, validating cure after treatment, and for screening prior to immunosuppression. We used a targeted analysis of open access 'omics' data sets and used online predictors to identify S. stercoralis proteins that are predicted to be present in infected stool, Strongyloides-specific, and antigenic. Transcriptomic data from gut and non-gut dwelling life cycle stages of S. stercoralis revealed 328 proteins that are differentially expressed. Strongyloides ratti proteomic data for excreted and secreted (E/S) proteins were matched to S. stercoralis, giving 1,057 orthologues. Five parasitism-associated protein families (SCP/TAPS, prolyl oligopeptidase, transthyretin-like, aspartic peptidase, acetylcholinesterase) were compared phylogenetically between S. stercoralis and outgroups, and proteins with least homology to the outgroups were selected. Proteins that overlapped between the transcriptomic and proteomic datasets were analysed by multiple sequence alignment, epitope prediction and 3D structure modelling to reveal S. stercoralis candidate peptide/protein coproantigens. We describe 22 candidates from seven genes, across all five protein families for further investigation as potential S. stercoralis diagnostic coproantigens, identified using open access data and freely-available protein analysis tools. This powerful approach can be applied to many parasitic infections with 'omic' data to accelerate development of specific diagnostic assays for laboratory or point-of-care field application.

Model-based aversive learning in humans is supported by preferential task state reactivation.

Harm avoidance is critical for survival, yet little is known regarding the neural mechanisms supporting avoidance in the absence of trial-and-error experience. Flexible avoidance may be supported by a mental model (i.e., model-based), a process for which neural reactivation and sequential replay have emerged as candidate mechanisms. During an aversive learning task, combined with magnetoencephalography, we show prospective and retrospective reactivation during planning and learning, respectively, coupled to evidence for sequential replay. Specifically, when individuals plan in an aversive context, we find preferential reactivation of subsequently chosen goal states. Stronger reactivation is associated with greater hippocampal theta power. At outcome receipt, unchosen goal states are reactivated regardless of outcome valence. Replay of paths leading to goal states was modulated by outcome valence, with aversive outcomes associated with stronger reverse replay than safe outcomes. Our findings are suggestive of avoidance involving simulation of unexperienced states through hippocampally mediated reactivation and replay.

Status of zinc nutrition in Bangladesh: the underlying associations.

Bangladesh is a country with a high burden of micronutrient malnutrition. Stunting affects 41 % of children aged under 5 years. Zn is one of the key micronutrients that is associated with stunting. The present study, as part of the national micronutrient survey 2011-2012, revealed for the first time the nationally representative prevalence of Zn deficiency and determined the associations of the condition. A cross-sectional 'nationwide' survey was conducted in pre-school-age children (6-59 months; PSAC) and non-pregnant non-lactating women (15-49 years; NPNLW). Multistage random sampling was done in 150 clusters; fifty in each of the rural, urban and slum strata. Data were analysed on 662 PSAC and 1073 NPNLW. Serum Zn was assayed by atomic absorption spectrophotometry. Zn deficiency was defined as serum Zn of <9·9 and <10·1 µmol/l in PSAC and NPNLW, respectively. The national prevalence of Zn deficiency was 44·6 and 57·3 % in PSAC and NPNLW, respectively. In PSAC, it was 29·5, 48·6 and 51·7 %, respectively, in urban, rural and slum strata. Household expenses (ß = 0·13; P = 0·007), Hb (ß = 0·10; P = 0·005), intake of animal-source Zn (ß = 0·096; P = 0·02) and asset score (ß = 0·11; P = 0·03) were positively associated with serum Zn in NPNLW. Residence in an urban area (ß = 0·33; P = 0·03) and intake of plant-origin Zn (ß = -0·13; P = 0·038) determined higher and lower status of Zn in PSAC, respectively. Zn deficiency was highly prevalent in Bangladesh, and it was principally related to inadequate quality of diet. To improve Zn nutrition, Bangladesh needs to strengthen research and programmes related to Zn biofortification, fortification and phytate-reducing technologies in the food system in the short and medium term. In addition, promotion of animal-source Zn for all is important in the long run.

Iodine deficiency disorders in Bangladesh, 2004-05: ten years of iodized salt intervention brings remarkable achievement in lowering goitre and iodine deficiency among children and women.

A survey was conducted to monitor the current status of iodine deficiency disorders in children aged 6-12 years and women aged 15-44 years in Bangladesh as measured by goitre prevalence and urinary iodine excretion. Conducted between September 2004 and March 2005, the survey followed a stratified multistage cluster sampling design to provide nationally representative data, with self-weighted rural-urban disaggregation. A total of 7233 children and 6408 women were examined for goitre and 4848 urine samples (2447 from children and 2401 from women) were analyzed for iodine. In addition, 5321 household salt samples were analyzed for iodine. In children, the total goitre rate (TGR) was 6.2%, compared to 49.9% in 1993 and the TGR among women was 11.7%, while in 1993 it was 55.6%. Prevalence of iodine deficiency (Urinary Iodine Excretion <100 microg/L) was 33.8% in children and 38.6% in women (compared to 71.0% and 70.2%, respectively in 1993). Iodine nutrition status in urban areas was considerably better than in rural areas. There was a clear inverse relationship between iodine deficiency and the coverage of households using adequately iodized salt (> or =15 ppm). The findings of the survey revealed that Bangladesh has achieved a commendable progress in reducing goitre rates and iodine deficiency among children and women ever since the universal salt iodization programme was instituted 10 years ago. However, physiological iodine deficiency still persists among more than one-third of children and women, which points to the need for all stakeholders to redouble their efforts in achieving universal salt iodization.