Monocytes prevent apoptosis of iPSCs and promote differentiation of kidney organoids.

Background: Induced pluripotent stem cells (iPSCs)-derived kidney organoids are a promising model for studying disease mechanisms and renal development. Despite several protocols having been developed, further improvements are needed to overcome existing limitations and enable a wider application of this model. One of the approaches to improve the differentiation of renal organoids in vitro is to include in the system cell types important for kidney organogenesis in vivo, such as macrophages.

Daily ritonavir-boosted darunavir for viral suppression in pregnancy (DRV-P).

Background: Ritonavir-boosted darunavir (DRV/r) is a preferred protease inhibitor in pregnant women living with HIV. Current practice at British Columbia's referral centre (the Oak Tree Clinic) is to dose DRV/r as 800/100 mg daily throughout pregnancy, although some guidelines recommend DRV/r 600/100 mg twice daily due to altered pharmacokinetics with once-daily dosing.

Objectives: We describe the effect of once-daily DRV/r on viral suppression, vertical transmission, adverse drug effects and adherence in pregnant women living with HIV.

A practical clinical guide to counselling on and managing contraception, pre-conception planning, and menopause for women living with HIV.

Background: Women represent one quarter of the population living with HIV in Canada and are an increasingly important sector of the HIV community. While some women's health issues such as cervical cancer screening and management are well addressed in HIV management guidelines, others are not. These include sexual and reproductive health factors such as contraception, pre-conception planning, and menopause.

Calcium dobesilate reduces SARS-CoV-2 entry into endothelial cells by inhibiting virus binding to heparan sulfate.

Recent reports demonstrate that SARS-CoV-2 utilizes cell surface heparan sulfate as an attachment factor to facilitate the initial interaction with host cells. Heparan sulfate interacts with the receptor binding domain of SARS-CoV-2 spike glycoprotein, and blocking this interaction can decrease cell infection. We and others reported recently that the family of compounds of 2,5-dihydroxyphenylic acid interferes with the binding of the positively charged groove in growth factor molecules to negatively charged cell surface heparan sulfate.

Post-partum contraception in women living with HIV.

Introduction: Rates of unintended pregnancy are higher in women living with HIV than in those without HIV. The World Health Organization and the Canadian HIV Pregnancy Planning Guidelines recommend preventing unintended pregnancies and offering contraception counselling to women living with HIV to reduce the rate of perinatal HIV transmission worldwide. No studies have assessed post-partum (PP) contraception use in women living with HIV in Canada.

Menopausal hormone therapy for women living with HIV.

People living with HIV are ageing, and a growing number of women living with HIV are entering menopause. Women living with HIV commonly have bothersome vasomotor symptoms and onset of menopause at earlier ages; both factors go on to affect quality of life and systemic health. Vasomotor symptoms and early menopause are both indications for menopausal hormone therapy; however, current evidence suggests that this therapy is seldom offered to women living with HIV.

TLR4 Response to LPS Is Reinforced by Urokinase Receptor.

GPI-anchored uPAR is the receptor for the extracellular serine protease urokinase-type plasminogen activator (uPA). Though uPAR role in inflammatory processes is documented, underlying mechanisms are not fully understood. In this study we demonstrate that uPAR is a part of Toll-like receptor 4 (TLR4) interactome.

Heparanase-2 protects from LPS-mediated endothelial injury by inhibiting TLR4 signalling.

The endothelial glycocalyx and its regulated shedding are important to vascular health. Endo-β-D-glucuronidase heparanase-1 (HPSE1) is the only enzyme that can shed heparan sulfate. However, the mechanisms are not well understood.

Will This Hospitalized Patient Develop Severe Alcohol Withdrawal Syndrome?: The Rational Clinical Examination Systematic Review.

Importance: Although severe alcohol withdrawal syndrome (SAWS) is associated with substantial morbidity and mortality, most at-risk patients will not develop this syndrome. Predicting its occurrence is important because the mortality rate is high when untreated.

Objective: To assess the accuracy and predictive value of symptoms and signs for identifying hospitalized patients at risk of SAWS, defined as delirium tremens, withdrawal seizure, or clinically diagnosed severe withdrawal.

The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative Systematic Review.

Background: In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC ≥ 400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC.

Determinants of neurological disease: Synthesis of systematic reviews.

Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome).

Learner : preceptor ratios for practice-based learning across health disciplines: a systematic review.

Context: Practice-based learning is a cornerstone of developing clinical and professional competence in health disciplines. Practice-based learning systems have many interacting components, but a key facet is the number of learners per preceptor. Different learner : preceptor ratios may have unique benefits and pose unique challenges for participants.

CHK1 and RAD51 activation after DNA damage is regulated via urokinase receptor/TLR4 signaling.

Mechanisms of DNA damage and repair signaling are not completely understood that hinder the efficiency of cancer therapy. Urokinase-type plasminogen activator receptor (PLAUR) is highly expressed in most solid cancers and serves as a marker of poor prognosis. We show that PLAUR actively promotes DNA repair in cancer cells.

Protein kinase C α inhibition prevents peritoneal damage in a mouse model of chronic peritoneal exposure to high-glucose dialysate.

Chronic exposure to commercial glucose-based peritoneal dialysis fluids during peritoneal dialysis induces peritoneal membrane damage leading to ultrafiltration failure. In this study the role of protein kinase C (PKC) α in peritoneal membrane damage was investigated in a mouse model of peritoneal dialysis. We used 2 different approaches: blockade of biological activity of PKCα by intraperitoneal application of the conventional PKC inhibitor Go6976 in C57BL/6 wild-type mice and PKCα-deficient mice on a 129/Sv genetic background.

Factors associated with onset, relapses or progression in multiple sclerosis: A systematic review.

Multiple sclerosis (MS) is a chronic disease of the central nervous system with an unidentified etiology. We systematically reviewed the literature on the possible risk factors associated with MS disease onset, relapses and progression from 1960 to 2012 by accessing six databases and including relevant systematic reviews, meta-analyses, case-control or cohort studies. The focus was on identifying modifiable risk factors.

SPECIFIC FEATURES OF CHRONORHYTH- MOLOGIC CHANGES OF THE ION-REGU- LATING FUNCTION OF THE KIDNEYS UN- DER THE HYPOFUNCTION OF THE PINEAL GLAND.

The paper investigates the specific features of chronorhythmologic changes of the ion-regulating function of the kidneys under the hypofunction of the pineal gland. For the study of hypofunction of the pineal gland, animals were maintained under constant light stimulation during 7 days. It has been established that the hypofunction epiphysis point out disturbances of the phasic structure of the ion-regulating function in relation to chronograms of the intact group of rats.

THE RATIO OF P53-PROAPOPTOTIC AND BCL-2 ANTIAPOPTOTIC ACTIVITY IN THE HIPPOCAMPUS OF RATS WITH BRAIN ISCHEMIA-REPERFUSION AND EXPERIMENTAL DIABETES.

The dynamics of the balance of indices of pro- and p53- Bcl-2 anti-apoptotic processes in the hippocampus of rats with experimental diabetes mellitus (DM) complicated by incomplete global cerebral ischemia-reperfusion was investigated. It is shown that p53 proapoptotic processes in animals without diabetes after 20 minutes of ischemia/l hour reperfusion in all fields of the hippocampus are activated in the background of increasing Bcl-2 antiapoptotic processes in the fields CAl, CA2, CA4 and depression of it - in the CA3 field. In the early postischemic period in rats with DM activity of the p53-proapoptotic processes in fields CAl, CA3, CA4 significantly exceeds that in non-diabetic rats (area of p53- IRM increases on 110, 60 and 27 %), and was significantly lower than that detected in CA2 field.

[Dynamics of changes of p53-positive cells morphofunctional condition in the cerebral cortex of the temporal lobe in rats affected by carotid ischemia-reperfusion].

The influence of bilateral 20-minute carotid ischemia with reperfusion of various duration upon the activity of apoptotic processes in the neurons and glia cells of the cerebral cortex in the temporal lobe of rats has been studied. Bilateral carotid ischemia with one-hour reperjusion has been indicated to increase the location density of p53+-neurocytes in this region of the cerebral cortex, increases percentage and density of p53+-nerve cells and reduces the percentage and density of p53+-glia cells on the 12th day of the post-ischemic period. Ischemic-reperfusion lesion of the brain increases the concentration of p53 protein in glia cells of the cerebral cortex in the temporal region in the early ischemic-reperfusion period and reduces it in nerve and glia cells in the late one.

Urokinase receptor mediates osteoclastogenesis via M-CSF release from osteoblasts and the c-Fms/PI3K/Akt/NF-κB pathway in osteoclasts.

Bone remodeling is a dynamic process based on a fine-tuned balance between formation and degradation of bone. Osteoblasts (OBLs) are responsible for bone formation and bone resorption is mediated by osteoclasts (OCLs). The mechanisms regulating the OBL-OCL balance are critical in health and disease; however, they are still far from being understood.