The Myocardial Unfolded Protein Response during Ischemic Cardiovascular Disease

Heart failure is a progressive and disabling disease. The incidence of heart failure is also on the rise, particularly in the elderly of industrialized societies. This is in part due to an increased ageing population, whom initially benefits from improved, and life-extending cardiovascular therapy, yet ultimately succumb to myocardial failure. A major cause of heart failure is ischemia secondary to the sequence of events that is dyslipidemia, atherosclerosis, and myocardial infarction. In the case of heart failure postmyocardial infarction, ischemia can lead to myocardial cell death by both necrosis and apoptosis. The extent of myocyte death postinfarction is associated with adverse cardiac remodeling that can contribute to progressive heart chamber dilation, ventricular wall thinning, and the onset of loss of cardiac function. In cardiomyocytes, recent studies indicate that myocardial ischemic injury activates the unfolded protein stress response (UPR) and this is associated with increased apoptosis. This paper focuses on the intersection of ischemia, the UPR, and cell death in cardiomyocytes. Targeting of the myocardial UPR may prove to be a viable target for the prevention of myocyte cell loss and the progression of heart failure due to ischemic injury

Expression patterns of chondrocyte genes cloned by differential display in tibial dyschondroplasia

AbstractTibial dyschondroplasia (TD) appears to involve a failure of the growth plate chondrocytes within growing long bones to differentiate fully to the hypertrophic stage, resulting in a mass of prehypertrophic chondrocytes which form the avascular TD lesion. Many biochemical and molecular markers of chondrocyte hypertrophy are absent from the lesion, or show reduced expression, but the cause of the disorder remains to be identified. As differentiation to the hypertrophic state is impaired in TD, we hypothesised that chondrocyte genes that are differentially expressed in the growth plate should show altered expression in TD. Using differential display, four genes, B-cadherin, EF2, HT7 and Ex-FABP were cloned from chondrocytes stimulated to differentiate to the hypertrophic stage in vitro, and their differential expression confirmed in vivo. Using semi-quantitative RT-PCR, the expression patterns of these genes were compared in chondrocytes from normal and TD growth plates. Surprisingly, none of these genes showed the pattern of expression that might be expected in TD lesion chondrocytes, and two of them, B-cadherin and Ex-FABP, were upregulated in the lesion. This indicates that the TD phenotype does not merely reflect the absence of hypertrophic marker genes, but may be influenced by more complex developmental mechanisms/defects than previously thought

The Effects of HIIT Versus MICT and Sedentary Controls on Blood Lipid Concentrations in Nondiabetic Overweight and Obese Young Adults: A Meta-analysis.

International Journal of Exercise Science 16(3): 791-813, 2023. With rates of obesity and dyslipidemia rising among young adults, this meta-analysis aimed to compare the effects of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) and sedentary controls (CON) on low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol (TC) in nondiabetic overweight and obese young adults to determine if HIIT or MICT is more efficacious in improving dyslipidemia. Studies included in the analysis had to be randomized controlled trials or quasi-experimental studies, comparing the effects of HIIT versus MICT or CON on at least three variables of interest: LDL, HDL, TG, and TC, in nondiabetic adults, with body mass indexes (BMIs) above 25, and average ages between 18-30. The quality of the studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. Eight studies fulfilled the selection criteria, with a mean PEDro quality score of 5.8. Compared to CON, HIIT significantly decreased the concentrations of LDL (-12.14 mg/dL, p = \u3c 0.00001) and TC (-9.27 mg/dL, p = 0.003), without significantly affecting HDL or TG. Compared to MICT, HIIT significantly decreased the concentrations of LDL (-6.23 mg/dL, p = 0.05) and TC (-7.85 mg/dL, p = 0.02), without significantly affecting HDL or TG concentrations. HIIT is superior to MICT and CON in improving the concentrations of LDL and TC in our target population. As early management of dyslipidemia improves long-term health, we recommend clinicians consider HIIT training protocols for their nondiabetic overweight and obese young adult patients

Comparison of Computational-Model and Experimental-Example Trained Neural Networks for Processing Speckled Fringe Patterns

The responses of artificial neural networks to experimental and model-generated inputs are compared for detection of damage in twisted fan blades using electronic holography. The training-set inputs, for this work, are experimentally generated characteristic patterns of the vibrating blades. The outputs are damage-flag indicators or second derivatives of the sensitivity-vector-projected displacement vectors from a finite element model. Artificial neural networks have been trained in the past with computational-model-generated training sets. This approach avoids the difficult inverse calculations traditionally used to compare interference fringes with the models. But the high modeling standards are hard to achieve, even with fan-blade finite-element models

Endoscopic Resection of Sinonasal Malignancy: A Systematic Review and Meta-analysis

OBJECTIVES: The use of endoscopic approaches for sinonasal malignancy resection has increased, but survival data are limited secondary to disease rarity and new surgical technique. Here we present a systematic review and meta-analysis of endoscopic endonasal resection of sinonasal malignancy. DATA SOURCES: MEDLINE, PubMed Central, NCBI Bookshelf, Cochrane Library, clinicaltrials.gov, National Guideline Clearinghouse. REVIEW METHODS: PRISMA/MOOSE guidelines were followed. MeSH terms were "endoscopic" AND ("esthesioneuroblastoma" OR "sinonasal adenocarcinoma" OR "squamous cell carcinoma" OR "sinonasal undifferentiated carcinoma"). For studies in which individual-level data were available, results were obtained by direct pooling. For studies in which only summary Kaplan-Meier curves were available, numerical data were extracted, traced, and aggregated by fitting a Weibull model. RESULTS: Of 320 studies identified, 35 case series were included (n = 952 patients), with 15 studies analyzed via aggregate modeling and 20 studies analyzed via direct pooling. Two- and 5-year survival rates for patients in aggregate modeling were 87.5% and 72.3%, respectively (mean follow-up: 32.9 months). Two- and 5-year survival for patients in direct pooling were 85.8% and 83.5%, respectively (mean follow-up: 43.0 ± 19.5 months). Significant overall survival difference was found between low- and high-grade cancers (P = .015) but not between low- and high-stage cancers (P = .79). CONCLUSION: Overall 2- and 5-year survival rates are comparable and sometimes greater than those from open craniofacial resection. Survival rates significantly differ by cancer grade but not stage. Journals and investigators should be encouraged to publish retrospective and prospective case series with staged survival updates based on established guidelines

The decline and conservation of bumblebees

Declines in bumblebee species in the last 60 years are well documented in Europe, where they are primarily driven by habitat loss and declines in floral abundance and diversity resulting from agricultural intensification. Impacts of habitat degradation and fragmentation are likely to be compounded by the social nature of bumblebees and their largely monogamous breeding system which renders their effective population size low. Hence populations are susceptible to stochastic extinction events and inbreeding. In North America, catastrophic declines of some bumblebee species since the 1990s are probably attributable to the accidental introduction of a non-native parasite from Europe, a result of global trade in domesticated bumblebee colonies used for pollination of greenhouse crops. Given the importance of bumblebees as pollinators of crops and wildflowers, it is vital that steps be taken to prevent further declines. Suggested measures include tight regulation of commercial bumblebee use and targeted use of agri-environment schemes to enhance floristic diversity in agricultural landscapes