12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing β cells and involves an interplay between β cells and cells of the innate and adaptive immune systems. We investigated the therapeutic potential of targeting 12-lipoxygenase (12-LOX), an enzyme implicated in inflammatory pathways in β cells and macrophages, using a mouse model in which the endogenous mouse Alox15 gene is replaced by the human ALOX12 gene. Our finding demonstrated that VLX-1005, a potent 12-LOX inhibitor, effectively delayed the onset of autoimmune diabetes in human gene replacement non-obese diabetic mice.

Inhibition of the Eukaryotic Initiation Factor-2-α Kinase PERK Decreases Risk of Autoimmune Diabetes in Mice.

Preventing the onset of autoimmune type 1 diabetes (T1D) is feasible through pharmacological interventions that target molecular stress-responsive mechanisms. Cellular stresses, such as nutrient deficiency, viral infection, or unfolded proteins, trigger the integrated stress response (ISR), which curtails protein synthesis by phosphorylating eIF2α. In T1D, maladaptive unfolded protein response (UPR) in insulin-producing β cells renders these cells susceptible to autoimmunity.

Inhibition of the eukaryotic initiation factor-2α kinase PERK decreases risk of autoimmune diabetes in mice.

Preventing the onset of autoimmune type 1 diabetes (T1D) is feasible through pharmacological interventions that target molecular stress-responsive mechanisms. Cellular stresses, such as nutrient deficiency, viral infection, or unfolded proteins, trigger the integrated stress response (ISR), which curtails protein synthesis by phosphorylating eukaryotic translation initiation factor-2α (eIF2α). In T1D, maladaptive unfolded protein response (UPR) in insulin-producing β cells renders these cells susceptible to autoimmunity.

Microglia undergo disease-associated transcriptional activation and CX3C motif chemokine receptor 1 expression regulates neurogenesis in the aged brain.

Adult neurogenesis continues throughout life but declines dramatically with age and in neurodegenerative disorders such as Alzheimer's disease. In parallel, microglia become activated resulting in chronic inflammation in the aged brain. A unique type of microglia, suggested to support neurogenesis, exists in the subventricular zone (SVZ), but little is known how they are affected by aging.

Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis.

Background: Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death.

Methods: We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice.

The use of filamentous hemagglutinin adhesin to detect immune responses to infections in layer hens.

is the aetiological agent of Spotty Liver Disease (SLD). SLD can cause significant production loss and mortalities among layer hens at and around peak of lay. We previously developed an enzyme linked immunosorbent assay (ELISA), SLD-ELISA1, to detect specific antibodies from bird sera using total proteins and sera pre-absorbed with proteins.

Prevalence of specific antibodies among commercial free-range layers in Australia.

Spotty liver disease (SLD) caused by affects the health and productivity of layer hens and is a disease of concern in poultry. In this study, blood and cloacal swab samples were collected from 709 birds across 11 free-range layer farms from different regions of Australia. The prevalence of specific antibodies and DNA was assessed using a specific ELISA and PCR and its correlation with mortalities and changes in egg production was analyzed to better understand the seroprevalence of in Australian free-range layer farms.

Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis.

The pathogeneses of the 2 major forms of diabetes, type 1 and type 2, differ with respect to their major molecular insults (loss of immune tolerance and onset of tissue insulin resistance, respectively). However, evidence suggests that dysfunction and/or death of insulin-producing β-cells is common to virtually all forms of diabetes. Although the mechanisms underlying β-cell dysfunction remain incompletely characterized, recent years have witnessed major advances in our understanding of the molecular pathways that contribute to the demise of the β-cell.

Assessment of plaque vulnerability in carotid atherosclerotic plaques using contrast-enhanced ultrasound.

Background: Atherosclerotic carotid plaques are one of the most important causes of stroke. Apart from the severity of stenosis, there are certain plaque characteristics such as neovascularization and, surface ulceration which makes a plaque vulnerable. This study was performed to study the plaque characteristics using contrast-enhanced ultrasound (CEUS) and evaluate their association with presence of ischemic cerebrovascular symptoms in these patients.

CAD-CAM denture teeth made on cast metal removable partial denture frameworks.

Once the fit of the cast metal framework on a removable partial denture (RPD) has been verified, the manufacturer's prefabricated denture teeth are typically secured on the cast metal framework to prepare for a wax evaluation. Although prefabricated denture teeth are available in different tooth forms and sizes, they require modification to fit an edentulous space. In arches with severe space discrepancy, it may be inefficient and time-consuming to make modifications to prefabricated denture teeth.

Mitofusins Mfn1 and Mfn2 Are Required to Preserve Glucose- but Not Incretin-Stimulated β-Cell Connectivity and Insulin Secretion.

Mitochondrial glucose metabolism is essential for stimulated insulin release from pancreatic β-cells. Whether mitofusin gene expression, and hence, mitochondrial network integrity, is important for glucose or incretin signaling has not previously been explored. Here, we generated mice with β-cell-selective, adult-restricted deletion knock-out (dKO) of the mitofusin genes Mfn1 and Mfn2 (βMfn1/2 dKO).

Vaccine effectiveness to protect against moderate or severe disease in COVID cases: A prospective cohort study.

Background: This study was carried out to evaluate the effectiveness of partial and full vaccination with ChAdOx1 nCoV-19 (COVISHIELD) to prevent the development of moderate or severe illness among COVID-positive cases.

Methods: This prospective cohort study was conducted among Armed Forces personnel deployed in Northern India who were found COVID positive during the study period between January and June 2021. Information about the vaccination status, age and comorbidities was collected at the time of diagnosis.

Fluorescently conjugated annular fibrin clot for multiplexed real-time digestion analysis.

Impaired fibrinolysis has long been considered as a risk factor for venous thromboembolism. Fibrin clots formed at physiological concentrations are promising substrates for monitoring fibrinolytic performance as they offer clot microstructures resembling . Here we introduce a fluorescently labeled fibrin clot lysis assay which leverages a unique annular clot geometry assayed using a microplate reader.

Isoquinoline alkaloids induce partial protection of laying hens from the impact of Campylobacter hepaticus (spotty liver disease) challenge.

Spotty liver disease (SLD) is a serious condition affecting extensively housed laying hens. The causative bacterium was described in 2015 and characterized in 2016 and named Campylobacter hepaticus. Antibiotics are the only tool currently available to combat SLD.

β-Cell autophagy in the pathogenesis of type 1 diabetes.

Type 1 diabetes is an insulin-dependent, autoimmune disease where the pancreatic β cells are destroyed resulting in hyperglycemia. This multifactorial disease involves multiple environmental and genetic factors, and has no clear etiology. Accumulating evidence suggests that early signaling defects within the β cells may promote a change in the local immune milieu leading to autoimmunity.

Pancreatic beta cell autophagy is impaired in type 1 diabetes.

Aims/hypothesis: Pancreatic beta cells are subjected to exogenous damaging factors such as proinflammatory cytokines or excess glucose that can cause accumulation of damage-inducing reactive oxygen species during the pathogenesis of diabetes. We and others have shown that beta cell autophagy can reduce reactive oxygen species to protect against apoptosis. While impaired islet autophagy has been demonstrated in human type 2 diabetes, it is unknown if islet autophagy is perturbed in the pathogenesis of type 1 diabetes.

Development of an enzyme-linked immunosorbent assay for detecting specific antibodies in chicken sera - a key tool in Spotty Liver Disease screening and vaccine development.

Spotty Liver Disease (SLD) is an emerging disease of serious concern in the egg production industry, as it causes significant egg loss and mortality in layer hens. The causative agent is a newly identified Gram-negative bacterium, and knowledge about pathogenesis and the potential for vaccine development is still in its infancy. Current detection methods for SLD, such as PCR and culturing, only detect an active infection and will not give any indication of a past infection from which the bacteria have been cleared.

Bacterial cellulose matrix with in situ impregnation of silver nanoparticles via catecholic redox chemistry for third degree burn wound healing.

In the present study, bacterial cellulose (BC) based nanocomposite dressing material was developed for third burn wound management by polydopamine (PD) coated BC with in situ reduction of silver nanoparticles (BC-PDAg). BC-PDAg nanocomposite was characterized to understand the morphological, physical and chemical properties. Antimicrobial activity of BC-PDAg against burn wound specific pathogens were significant.

MRI Changes in the Temporomandibular Joint after Mandibular Advancement.

Purpose: Esthetic dental and skeletal component correction can affect the temporomandibular joint (TMJ). Arthrogenic TMJ dysfunction can be present in the joint at the outset or it can develop during the treatment or later. The aim of the present study was to examine the changes found on magnetic resonance imaging (MRI) studies of the TMJ in patients with skeletal Class II malocclusion who had undergone combined orthodontic and bilateral sagittal split ramus osteotomy (BSSRO) advancement.

Dental care during pregnancy based on the pregnancy risk assessment monitoring system in Utah.

Background: Although receiving dental care is recommended for women during pregnancy, getting such care remains low. This study will identify the level of dental care received during pregnancy and factors associated with care for a group of pregnant women in Utah.

Methods: Analyses were based on 2793 pregnant women completing the 2014-2015 Utah PRAMS survey.