137 research outputs found
The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α-1 anti-trypsin deficiency.
The serine proteinase inhibitor α-1 anti-trypsin (AAT) provides an antiprotease protective screen throughout the body. Mutations in the AAT gene (SERPINA1) that lead to deficiency in AAT are associated with chronic obstructive pulmonary diseases. The Z mutation encodes a misfolded variant of AAT that is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum of hepatocytes and other AAT-producing cells. Until recently, it was thought that loss of antiprotease function was the major cause of ZAAT-related lung disease. However, the contribution of gain-of-function effects is now being recognized. Here we describe how both loss- and gain-of-function effects can contribute to ZAAT-related lung disease. In addition, we explore how SERPINA1 heterozygosity could contribute to smoking-induced chronic obstructive pulmonary diseases and consider the consequences
Voluntary activation failure is detectable in some myositis patients with persisting quadriceps femoris weakness: an observational study
This cross-sectional, observational study was undertaken to examine whether voluntary activation failure could contribute to the persisting weakness observed in some patients with treated idiopathic inflammatory myositis. In 20 patients with myositis of more than six months' duration (5 males, 15 females; mean [± 1 SD] age 53 [11] years) and 102 normal subjects (44 males, 58 females; mean age 32 [8] years), isometric maximum voluntary contractions (MVCs) of the dominant quadriceps femoris (QF) were quantified. Absolute MVC results of normal subjects and patients were then normalised with respect to lean body mass (force per units of lean body mass), giving a result in Newtons per kilogram. Based on mass-normalised force data of normal subjects, patients were arbitrarily stratified into "weak" and "not weak" subgroups. During further MVC attempts, the "twitch interpolation" technique was used to assess whether the QF voluntary activation of patients was complete. This technique relies on the fact that, because muscle activation is incomplete during submaximal voluntary contractions, electrical stimulation of the muscle can induce force increments superimposed on the submaximal voluntary force being generated. No between-gender differences were seen in the mass-normalised MVC results of healthy subjects, so the gender-combined results of 6.6 (1.5) N/kg were used for patient stratification. No between-gender difference was found for mass-normalised MVCs in patients: males 5.4 (3.2) and females 3.0 (1.7) N/kg (p > 0.05). Mass-normalised MVCs of male patients were as great as those of normal subjects (p > 0.05), but mass-normalised MVCs of female patients were significantly smaller than those of the normal subjects (p < 0.001). Only one of the six "not weak" patients exhibited interpolated twitches during electrical stimulation, but six of the 14 "weak" patients did, the biggest twitches being seen in the weakest patient. That interpolated twitches can be induced in some myositis patients with ongoing QF weakness during supposed MVCs clearly suggests that voluntary activation failure does contribute to QF weakness in those patients
Long noncoding RNA are aberrantly expressed in vivo in the cystic fibrosis bronchial epithelium.
Long non-coding RNAs (lncRNAs) have emerged recently as key regulatory molecules with diverse roles at almost every level of the regulation of gene expression. The roles of these RNAs in the pathogenesis of cystic fibrosis (CF); a lethal multisystem, autosomal recessive disorder have yet to be explored. Our aim was to examine the expression profile of lncRNA, in the airway epithelium of people with CF. We examined the expression of 30,586 lncRNAs by microarray (Human LncRNA Array v3.0, Arraystar, Inc.), in vivo in bronchial cells isolated from endobronchial brushings obtained from CF and non-CF individuals. In total, we identified 1,063 lncRNAs with differential expression between CF and non-CF individuals (fold change ≥3, p≤0.001). The microarray also contained probes for ∼26,109 protein coding transcripts, of which 720 were differentially expressed between CF and non-CF brush samples (fold change ≥3, p≤0.001). Confirmation of a selection of differentially expressed coding mRNA and lncRNA transcripts such as XIST and TLR8 was achieved using qRT-PCR. Gene ontology bioinformatics analysis highlighted that many processes over-represented in the CF bronchial epithelium are related to inflammation. These data show a significantly altered lncRNA and mRNA expression profile in CF bronchial cells in vivo. Dysregulation of some of these lncRNAs may play important roles in the chronic infection and inflammation that exists in the lungs of people with CF
An intervention trial to determine the response of vitamin B12 biomarkers to chronic supplementation with low dose vitamin B12 after folate repletion
Moderate-intensity aerobic and resistance exercise is safe and favorably influences body composition in patients with quiescent Inflammatory Bowel Disease: a randomized controlled cross-over trial
peer-reviewedBackground
Overweight and metabolic problems now add to the burden of illness in patients with Inflammatory Bowel Disease. We aimed to determine if a program of aerobic and resistance exercise could safely achieve body composition changes in patients with Inflammatory Bowel Disease.
Methods
A randomized, cross-over trial of eight weeks combined aerobic and resistance training on body composition assessed by Dual Energy X-ray Absorptiometry was performed. Patients in clinical remission and physically inactive with a mean age of 25 ± 6.5 years and Body Mass Index of 28.9 ± 3.8 were recruited from a dedicated Inflammatory Bowel Disease clinic. Serum cytokines were quantified, and microbiota assessed using metagenomic sequencing.
Results
Improved physical fitness was demonstrated in the exercise group by increases in median estimated VO2max (Baseline: 43.41mls/kg/min; post-intervention: 46.01mls/kg/min; p = 0.03). Improvement in body composition was achieved by the intervention group (n = 13) with a median decrease of 2.1% body fat compared with a non-exercising group (n = 7) (0.1% increase; p = 0.022). Lean tissue mass increased by a median of 1.59 kg and fat mass decreased by a median of 1.52 kg in the exercising group. No patients experienced a deterioration in disease activity scores during the exercise intervention. No clinically significant alterations in the α- and β-diversity of gut microbiota and associated metabolic pathways were evident.
Conclusions
Moderate-intensity combined aerobic and resistance training is safe in physically unfit patients with quiescent Inflammatory Bowel Disease and can quickly achieve favourable body compositional changes without adverse effects.
Trial registration
The study was registered at ClinicalTrials.gov; Trial number:
NCT02463916
B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study
Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60–88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9–1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28–13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing
Dairy intakes in older Irish adults and effects on vitamin micronutrient status: Data from the TUDA study
Consumption of dairy products has been associated with positive health outcomes including a lower risk of hypertension, improved bone health and a reduction in the risk of type 2 diabetes. The suggested dairy intake for health in older adults is three servings per day but recent analysis of the NHANES data for older adults reported 98% were not meeting these recommendations. No studies have investigated the consequences of such declines in the dairy intakes of Irish older adults and the subsequent effects on vitamin micronutrient status
Greater yogurt consumption is associated with increased bone mineral density and physical function in older adults
The association between proton pump inhibitors and hyperparathyroidism - a potential mechanism for increased fracture - results of a large observational cohort study
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