Long-term increase of fat mass after a four week intervention with fast food based hyper-alimentation and limitation of physical activity

<p>Abstract</p> <p>Background</p> <p>A sedentary lifestyle and increased consumption of energy dense food have become more common in many parts of the world. The aim of this study was to study long term effects on body composition after a four week intervention with fast food based hyper-alimentation and limited physical activity in young normal weight subjects.</p> <p>Methods</p> <p>Eighteen subjects, mean age 26 (6.6) years, increased their energy intake with in average 70% and physical activity were not to exceed 5000 steps/day. Body composition was measured by Dual energy x-ray (DXA) at baseline, after the intervention and after 12 months. A matched control group was also included. ANOVA and Student's paired and unpaired t-test were used.</p> <p>Results</p> <p>During the intervention body weight increased with 6.4 (2.8) kg and DXA measurements showed increases of both fat free mass and fat mass. Six months after the intervention the subjects had lost most of the weight gain, - 4.7 (3.1) kg. Twelve months after the intervention body weight had increased with 1.5 (2.4) kg compared to baseline (p = 0.018). DXA measurements at 12 months showed unchanged fat free mass compared to baseline but higher fat mass, + 1.4 (1.9) kg (p = 0.01). After 2.5 years the increase of body weight was 3.1 (4.0) kg (p = 0.01) while there was no change in controls compared to baseline, + 0.1(2.5) kg (p = 0.88).</p> <p>Conclusion</p> <p>One year after a short term intervention with increased fast food based hyper-alimentation there was an increase of fat mass but unchanged fat free mass. As the change of fat mass was larger than expected from prospective epidemiological studies and as there was no increase of body weight in controls it raises the issue whether there is a long-term effect to increase fat mass of a short period of hyper-alimentation.</p

Improving Standards of Care in Obstructed Labour: A Criteria-Based Audit at a Referral Hospital in a Low-Resource Setting in Tanzania

Objective In low-resource settings, obstructed labour is strongly associated with severe maternal morbidity and intrapartum asphyxia, and consequently maternal and perinatal deaths. This study evaluated the impact of a criteria-based audit of the diagnosis and management of obstructed labour in a low-resource setting. Methods A baseline criteria-based audit was conducted from October 2013 to March 2014, followed by a workshop in which stakeholders gave feedback on interventions agreed upon to improve obstetric care. The implemented interventions included but were not limited to introducing standard guidelines for diagnosis and management of obstructed labour, agreeing on mandatory review by specialist for cases that are assigned caesarean section, re-training and supervision on use and interpretation of partograph and, strengthening team work between doctors, mid-wives and theatre staff. After implementing these interventions in March, a re-audit was performed from July 2015 to November, 2015, and the results were compared to those of the baseline audit. Results Two hundred and sixty deliveries in the baseline survey and 250 deliveries in the follow-up survey were audited. Implementing the new criteria improved the diagnosis from 74% to 81% (p = 0.049) and also the management of obstructed labour from 4.2% at baseline audit to 9.2% at re-audit (p = 0.025). Improved detection of prolonged labour through heightened observation of regular contractions, protracted cervical dilatation, protracted descent of presenting part, arrested cervical dilation, and severe moulding contributed to improved standards of diagnosis (all p \u3c 0.04). Patient reviews by senior obstetricians increased from 34% to 43% (p = 0.045) and reduced time for caesarean section intervention from the median time of 120 to 90 minutes (p = 0.001) improved management (all p \u3c 0.05). Perinatal outcomes, neonatal distress and fresh stillbirths, were reduced from 16% to. 8.8% (p = 0.01). Conclusion A criteria-based audit proved to be a feasible and useful tool in improving diagnosis and management of obstructed labour using available resources. Some of the observed changes in practice were of modest magnitude implying demand for further improvements, while sustaining those already put in place

Alcohol-induced decrease in muscle protein synthesis associated with increased binding of mTOR and raptor: Comparable effects in young and mature rats

<p>Abstract</p> <p>Background</p> <p>Acute alcohol (EtOH) intoxication decreases muscle protein synthesis via inhibition of mTOR-dependent translation initiation. However, these studies have been performed in relatively young rapidly growing rats in which muscle protein accretion is more sensitive to growth factor and nutrient stimulation. Furthermore, some in vivo-produced effects of EtOH vary in an age-dependent manner. The hypothesis tested in the present study was that young rats will show a more pronounced decrement in muscle protein synthesis than older mature rats in response to acute EtOH intoxication.</p> <p>Methods</p> <p>Male F344 rats were studied at approximately 3 (young) or 12 (mature) months of age. Young rats were injected intraperitoneally with 75 mmol/kg of EtOH, and mature rats injected with either 75 or 90 mmol/kg EtOH. Time-matched saline-injected control rats were included for both age groups. Gastrocnemius protein synthesis and the activity of the mTOR pathway were assessed 2.5 h after EtOH using [³H]-labeled phenylalanine and the phosphorylation of various protein factors known to regulate peptide-chain initiation.</p> <p>Results</p> <p>Blood alcohol levels (BALs) were lower in mature rats compared to young rats after administration of 75 mmol/kg EtOH (154 ± 23 vs 265 ± 24 mg/dL). However, injection of 90 mmol/kg EtOH in mature rats produced BALs comparable to that of young rats (281 ± 33 mg/dL). EtOH decreased muscle protein synthesis similarly in both young and high-dose EtOH-treated mature rats. The EtOH-induced changes in both groups were associated with a concomitant reduction in 4E-BP1 phosphorylation, and redistribution of eIF4E between the active eIF4E·eIF4G and inactive eIF4E·4EBP1 complex. Moreover, EtOH increased the binding of mTOR with raptor in a manner which appeared to be AMPK- and TSC-independent. In contrast, although muscle protein synthesis was unchanged in mature rats given low-dose EtOH, compared to control values, the phosphorylation of rpS6 and eIF4G was decreased.</p> <p>Conclusion</p> <p>These data indicate that muscle protein synthesis is equally sensitive to the inhibitory effects of EtOH in young rapidly growing rats and older mature rats which are growing more slowly, but that mature rats must be given a relatively larger dose of EtOH to achieve the same BAL. Based on the differential response in mature rats to low- and high-dose EtOH, the decreased protein synthesis was associated with a reduction in mTOR activity which was selectively mediated via a reduction in 4E-BP1 phosphorylation and an increase in mTOR·raptor formation.</p

Grazing protozoa and the evolution of the Escherichia coli O157:H7 Shiga toxin-encoding prophage

Humans play little role in the epidemiology of Escherichia coli O157:H7, a commensal bacterium of cattle. Why then does E. coli O157:H7 code for virulence determinants, like the Shiga toxins (Stxs), responsible for the morbidity and mortality of colonized humans? One possibility is that the virulence of these bacteria to humans is coincidental and these virulence factors evolved for and are maintained for other roles they play in the ecology of these bacteria. Here, we test the hypothesis that the carriage of the Stx-encoding prophage of E. coli O157:H7 increases the rate of survival of E. coli in the presence of grazing protozoa, Tetrahymena pyriformis. In the presence but not the absence of Tetrahymena, the carriage of the Stx-encoding prophage considerably augments the fitness of E. coli K-12 as well as clinical isolates of E. coli O157 by increasing the rate of survival of the bacteria in the food vacuoles of these ciliates. Grazing protozoa in the environment or natural host are likely to play a significant role in the ecology and maintenance of the Stx-encoding prophage of E. coli O157:H7 and may well contribute to the evolution of the virulence of these bacteria to colonize humans

The Stroke-Induced Increase of Somatostatin-Expressing Neurons is Inhibited by Diabetes: A Potential Mechanism at the Basis of Impaired Stroke Recovery

Type 2 diabetes (T2D) hampers recovery after stroke, but the underling mechanisms are mostly unknown. In a recently published study (Pintana et al. in Clin Sci (Lond) 133(13):1367\u20131386, 2019), we showed that impaired recovery in T2D was associated with persistent atrophy of parvalbumin+ interneurons in the damaged striatum. In the current work, which is an extension of the abovementioned study, we investigated whether somatostatin (SOM)+ interneurons are also affected by T2D during the stroke recovery phase. C57Bl/6j mice were fed with high-fat diet or standard diet (SD) for 12\ua0months and subjected to 30-min transient middle cerebral artery occlusion (tMCAO). SOM+ cell number/density in the striatum was assessed by immunohistochemistry 2 and 6\ua0weeks after tMCAO in peri-infarct and infarct areas. This was possible by establishing a computer-based quantification method that compensates the post-stroke tissue deformation and the irregular cell distribution. SOM+ interneurons largely survived the stroke as seen at 2\ua0weeks. Remarkably, 6\ua0weeks after stroke, the number of SOM+ interneurons increased (vs. contralateral striatum) in SD-fed mice in both peri-infarct and infarct areas. However, this increase did not result from neurogenesis. T2D completely abolished this effect specifically in the in the infarct area. The results suggest that the up-regulation of SOM expression in the post-stroke phase could be related to neurological recovery and T2D could inhibit this process. We also present a new and precise method for cell counting in the stroke-damaged striatum that allows to reveal accurate, area-related effects of stroke on cell number

Hepatitis e Virus Genotype 3 Genomes from RNA-Positive but Serologically Negative Plasma Donors Have CUG as the Start Codon for ORF3

Hepatitis E virus (HEV) is a pathogen that causes hepatitis worldwide. Molecular studies have identified HEV RNA in blood products although its significance is not understood. This study was undertaken to characterize HEV genomes in asymptomatic plasma donors from Sweden and Germany lacking anti-HEV. Complete open reading frames (ORFs) were obtained from HEV strains in 5 out of 18 plasma donors who tested positive for HEV RNA. All strains had CUG as the start codon of ORF3, while 147 GenBank strains all had AUG as the start codon (p &lt; 0.0001). This substitution was found in both interrelated and unrelated strains belonging to different phylogenetic clades. The HEV strains from the seronegative plasma donors had no other substitution in common, which may be why the CUG substitution seems to explain the seronegativity

Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals A beta Aggregation Dependent Anionic Lipid Accumulations and Metabolism

Amyloid plaque formation constitutes one of the main pathological hallmarks of Alzheimer’s disease (AD) and is suggested to be a critical factor driving disease pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, Aβ deposits are predominantly of diffuse morphology suggesting that cored plaque formation is primarily associated with cognitive deterioration and AD pathogenesis. Little is known about the molecular mechanism responsible for conversion of monomeric Aβ into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among Aβ plaques, including cored/compact- and diffuse, may be linked to their distinct Aβ profile and other chemical species including neuronal lipids. We developed a novel, chemical imaging paradigm combining matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) and fluorescent amyloid staining. This multimodal imaging approach was used to probe the lipid chemistry associated with structural plaque heterogeneity in transgenic AD mice (tgAPPSwe) and was correlated to Aβ profiles determined by subsequent laser microdissection and immunoprecipitation-mass spectrometry. Multivariate image analysis revealed an inverse localization of ceramides and their matching metabolites to diffuse and cored structures within single plaques, respectively. Moreover, phosphatidylinositols implicated in AD pathogenesis, were found to localize to the diffuse Aβ structures and correlate with Aβ1–42. Further, lysophospholipids implicated in neuroinflammation were increased in all Aβ deposits. The results support previous clinical findings on the importance of lipid disturbances in AD pathophysiology and associated sphingolipid processing. These data highlight the potential of multimodal imaging as a powerful technology to probe neuropathological mechanisms

Generalized Geologic Map of South Carolina 2005

This color map shows the geology of South Carolina, including coastal plain, triassic, Blue Ridge and Piedmont, intrusive igneous rocks, significant structural features and significant wave-cut scarps