Caldwellbennedsen2902

Huntington's disease (HD) is a fatal and progressive condition with severe debilitating motor defects and muscle weakness. Although classically recognized as a neurodegenerative disorder, there is increasing evidence of cell autonomous toxicity in skeletal muscle. We recently demonstrated that skeletal muscle fibers from the R6/2 model mouse of HD have a decrease in specific membrane capacitance, suggesting a loss of transverse tubule (t-tubule) membrane in R6/2 muscle. A previous report also indicated that Cav1.1 current was reduced in R6/2 skeletal muscle, suggesting defects in excitation-contraction (EC) coupling. Thus, we hypothesized that a loss and/or disruption of the skeletal muscle t-tubule system contributes to changes in EC coupling in R6/2 skeletal muscle. We used live-cell imaging with multiphoton confocal microscopy and transmission electron microscopy to assess the t-tubule architecture in late-stage R6/2 muscle and found no significant differences in the t-tubule system density, regularity, or integrity. However, electron microscopy images revealed that the cross-sectional area of t-tubules at the triad were 25% smaller in R6/2 compared with age-matched control skeletal muscle. Computer simulation revealed that the resulting decrease in the R6/2 t-tubule luminal conductance contributed to, but did not fully explain, the reduced R6/2 membrane capacitance. Analyses of bridging integrator-1 (Bin1), which plays a primary role in t-tubule formation, revealed decreased Bin1 protein levels and aberrant splicing of Bin1 mRNA in R6/2 muscle. Additionally, the distance between the t-tubule and sarcoplasmic reticulum was wider in R6/2 compared with control muscle, which was associated with a decrease in junctophilin 1 and 2 mRNA levels. Altogether, these findings can help explain dysregulated EC coupling and motor impairment in Huntington's disease.A recent formulation of predictive coding theory proposes that a subset of neurons in each cortical area encodes sensory prediction errors, the difference between predictions relayed from higher cortex and the sensory input. Here, we test for evidence of prediction error responses in spiking responses and local field potentials (LFP) recorded in primary visual cortex and area V4 of macaque monkeys, and in complementary electroencephalographic (EEG) scalp recordings in human participants. We presented a fixed sequence of visual stimuli on most trials, and violated the expected ordering on a small subset of trials. Under predictive coding theory, pattern-violating stimuli should trigger robust prediction errors, but we found that spiking, LFP and EEG responses to expected and pattern-violating stimuli were nearly identical. Our results challenge the assertion that a fundamental computational motif in sensory cortex is to signal prediction errors, at least those based on predictions derived from temporal patterns of visual stimulation.In the present work, different brands of baby formula and cereal consumed in Jordan were analyzed for their radioactivity content. The activity concentrations of 40K varied with the designated age group in formula with the average concentrations being (in Bq/kg) 160.2 ± 33.5, 219.0 ± 35.0 and 265.2 ± 56.3 for the age groups of 0-6 months, 6-12 months and 1-3 years, respectively. 226Ra was not detected in any of the samples, while 232Th was detected in nearly half the samples with concentrations ranging from 0.22 to 0.82 Bq/kg. 137Cs was detected in only two samples with concentrations of 0.94 and 3.15 Bq/kg. The concentrations of 40K and 232Th in cereal were in the ranges of 23-294 and 0.49-1.48 Bq/kg, respectively. The resulting committed dose was assessed and found in the range of 154-613 μSv, with insignificant contribution from 137Cs, which is within the worldwide range but generally higher than the worldwide average of 290 μSv.

Meta-analyses of randomized clinical trials have indicated that improved hypertension control reduces the risk for cognitive impairment and dementia. However, it is unclear to what extent pathways reflective of Alzheimer disease (AD) pathology are affected by hypertension control.

To evaluate the association of intensive blood pressure control on AD-related brain biomarkers.

This is a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT MIND), a multicenter randomized clinical trial that compared the efficacy of 2 different blood pressure-lowering strategies. Potential participants (n = 1267) 50 years or older with hypertension and without a history of diabetes or stroke were approached for a brain magnetic resonance imaging (MRI) study. Of these, 205 participants were deemed ineligible and 269 did not agree to participate; 673 and 454 participants completed brain MRI at baseline and at 4-year follow-up, respectively; the final follow-up date was July 1, 2016. Analysis began September 2019rebral blood flow, or mean fractional anisotropy.

Intensive treatment was associated with a small but statistically significant greater decrease in hippocampal volume compared with standard treatment, consistent with the observation that intensive treatment is associated with greater decreases in total brain volume. However, intensive treatment was not associated with changes in any of the other MRI biomarkers of AD compared with standard treatment.

ClinicalTrials.gov Identifier NCT01206062.

ClinicalTrials.gov Identifier NCT01206062.

Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown.

To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease.

This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies-147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. Selleckchem AZD9291 This analysis was conducted from January to June 2020.

Fish consumption was recorded using validated fassociated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease.

Digital tomosynthesis (DTS) is currently undergoing validation for potential clinical implications. The aim of this study was to investigate the potential for DTS as a low-dose alternative to computed tomography (CT) in imaging of pulmonary pathology in patients with cystic fibrosis (CF).

DTS and CT were performed as part of the routine triannual follow-up in 31 CF patients. Extent of disease was quantified according to modality-specific scoring systems. Statistical analysis included Spearman's rank correlation coefficient (r) and Krippendorff's alpha (α).

The median effective dose was 0.14 for DTS and 2.68 for CT. Intermodality correlation was very strong for total score and the subscores regarding bronchiectasis and bronchial wall-thickening (r=0.82-0.91, P<0.01). Interobserver reliability was high for total score, bronchiectasis and mucus plugging (α=0.83-0.93) in DTS.

Chest tomosynthesis could be a low-dose alternative to CT in quantitative estimation of structural lung disease in CF.

Chest tomosynthesis could be a low-dose alternative to CT in quantitative estimation of structural lung disease in CF.The radiation protection programme is aimed at safe usage of radiation at workplace, ensuring minimum possible dose to radiation workers, patients and members of the public. Verification of the adequacy of protective measures in actual workplace is important, especially for diagnostic radiology facilities, as a substantial number of suspected overexposures are reported from these facilities. To address this issue, a study was conducted for mapping workplace radiation field at various locations in nine Diagnostic Radiology Facilities of two hospitals in India. The cumulative doses were measured for a period of 1-3 months, using personnel monitoring TLD badges. The dosemeters were placed at positions representative of two exposure situations (1) probable locations of workers during procedures, leading to genuine exposure and (2) inappropriate storage locations of personal dosemeters at user end for probing claims of nongenuine exposures. The results indicate that the measured doses at locations (1) were just a fraction of the permissible dose, provided all safety practices are adhered to. However, the measured doses at certain locations (2) exceeded the investigation levels and indicate that any inadvertent storage of the dosemeters at such locations could lead to reporting of the overexposure from these radiology facilities. The outcome of the study will be useful for the investigation of such exposures and better understanding of the readout patterns of TLD badges in radiology workplaces.

It is unclear which umbilical cord management strategy is the best for preventing mortality and morbidities in preterm infants.

To systematically review and conduct a network meta-analysis comparing 4 umbilical cord management strategies for preterm infants immediate umbilical cord clamping (ICC), delayed umbilical cord clamping (DCC), umbilical cord milking (UCM), and UCM and DCC.

PubMed, Embase, CINAHL, and Cochrane CENTRAL databases were searched from inception until September 11, 2020.

Randomized clinical trials comparing different umbilical cord management strategies for preterm infants were included.

Data were extracted for bayesian random-effects meta-analysis to estimate the relative treatment effects (odds ratios [OR] and 95% credible intervals [CrI]) and surface under the cumulative ranking curve values.

The primary outcome was predischarge mortality. The secondary outcomes were intraventricular hemorrhage, severe intraventricular hemorrhage, need for packed red blood cell transfusion, aith the lower odds of mortality in preterm infants. Compared with ICC, DCC and UCM were associated with reductions in intraventricular hemorrhage and need for packed red cell transfusion. There was no significant difference between UCM and DCC for any outcome. Further studies directly comparing DCC and UCM are needed.

Compared with ICC, DCC was associated with the lower odds of mortality in preterm infants. Compared with ICC, DCC and UCM were associated with reductions in intraventricular hemorrhage and need for packed red cell transfusion. There was no significant difference between UCM and DCC for any outcome. Further studies directly comparing DCC and UCM are needed.

A combination of conservative treatments is commonly used in clinical practice for thumb base osteoarthritis despite limited evidence for this approach.

To determine the efficacy of a 6-week combination of conservative treatments compared with an education comparator.

Randomized, parallel trial with 11 allocation ratio among people aged 40 years and older with symptomatic and radiographic thumb base osteoarthritis in a community setting in Australia.

The intervention group (n = 102) received education on self-management and ergonomic principles, a base-of-thumb splint, hand exercises, and diclofenac sodium, 1%, gel. The comparator group (n = 102) received education on self-management and ergonomic principles alone. Intervention use was at participants' discretion from 6 to 12 weeks.

Hand function (Functional Index for Hand Osteoarthritis; 0-30) and pain (visual analog scale; 0-100 mm) were measured at week 6 (primary time point) and week 12. An α of .027 was used at week 6 to account for co-primary outcomes.