Mitochondrial calcium uniporter channel gatekeeping in cardiovascular disease.

The mitochondrial calcium (Ca) uniporter channel (mtCU) resides at the inner mitochondrial membrane and is required for Ca to enter the mitochondrial matrix. The mtCU is essential for cellular function, as Ca regulates metabolism, bioenergetics, signaling pathways and cell death. Ca uptake is primarily regulated by the MICU family (MICU1, MICU2, MICU3), EF-hand-containing Ca-sensing proteins, which respond to cytosolic Ca concentrations to modulate mtCU activity.

A Retinoic Acid:YAP1 signaling axis controls atrial lineage commitment.

Vitamin A/Retinoic Acid (Vit A/RA) signaling is essential for heart development. In cardiac progenitor cells (CPCs), RA signaling induces the expression of atrial lineage genes while repressing ventricular genes, thereby promoting the acquisition of an atrial cardiomyocyte cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is not fully identified.

Genetic ablation of neuronal mitochondrial calcium uptake halts Alzheimer's disease progression.

Alzheimer's disease (AD) is characterized by the extracellular deposition of amyloid beta, intracellular neurofibrillary tangles, synaptic dysfunction, and neuronal cell death. These phenotypes correlate with and are linked to elevated neuronal intracellular calcium ( Ca ) levels. Recently, our group reported that mitochondrial calcium ( Ca ) overload, due to loss of Ca efflux capacity, contributes to AD development and progression.

TMEM65 regulates NCLX-dependent mitochondrial calcium efflux.

The balance between mitochondrial calcium (Ca) uptake and efflux regulates ATP production, but if perturbed causes energy starvation or Ca overload and cell death. The mitochondrial sodium-calcium exchanger, NCLX, is a critical route of Ca efflux in excitable tissues, such as the heart and brain, and animal models support NCLX as a promising therapeutic target to limit pathogenic Ca overload. However, the mechanisms that regulate NCLX activity remain largely unknown.

Signaling pathways regulating mitochondrial calcium efflux - a commentary on Rozenfeld et al. "Essential role of the mitochondrial Na/Ca exchanger NCLX in mediating PDE2-dependent neuronal survival and learning".

Mitochondrial calcium (Ca) is a critical regulator of neuronal cell death, bioenergetics, and signaling pathways. Although the regulatory machinery governing Ca uptake via the mitochondrial calcium uniporter (mtCU) has been identified and functionally characterized, regulation of the mitochondrial Na/Ca exchanger (NCLX), the primary means of Ca efflux, is poorly understood. Rozenfeld et al.

Neuronal loss of NCLX-dependent mitochondrial calcium efflux mediates age-associated cognitive decline.

Mitochondrial calcium overload contributes to neurodegenerative disease development and progression. We recently reported that loss of the mitochondrial sodium/calcium exchanger (NCLX), the primary mechanism of Ca efflux, promotes Ca overload, metabolic derangement, redox stress, and cognitive decline in models of Alzheimer's disease (AD). However, whether disrupted Ca signaling contributes to neuronal pathology and cognitive decline independent of pre-existing amyloid or tau pathology remains unknown.

Helicobacter pylori World Gastroenterology Organization Global Guideline.

Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission.

Saccharomyces boulardii CNCM I-745 supplementation modifies the fecal resistome during Helicobacter pylori eradication therapy.

Background: The gut microbiota is a significant reservoir of antimicrobial resistance genes (ARGs). The use and misuse of antimicrobials can select multi-resistant bacteria and modify the repertoire of ARGs in the gut. Developing effective interventions to manipulate the intestinal resistome would allow us to modify the antimicrobial resistance risk.

Physician Perceptions on the Use of Antibiotics and Probiotics in Adults: An International Survey in the Asia-Pacific Area.

Background And Aims: The over-prescription of antibiotics is thought to represent a major threat to public health worldwide and is more frequently observed in some low- and middle-income countries. In the Asia-Pacific region, economic development, health care organization and population demographics are very heterogenous. The objective of this survey was to investigate antibiotic use and probiotic co-prescription among adult patients in this area.

Antibiotics as Major Disruptors of Gut Microbiota.

Advances in culture-independent research techniques have led to an increased understanding of the gut microbiota and the role it plays in health and disease. The intestine is populated by a complex microbial community that is organized around a network of metabolic interdependencies. It is now understood that the gut microbiota is vital for normal development and functioning of the human body, especially for the priming and maturation of the adaptive immune system.

Duodenal microbiome in patients with or without Helicobacter pylori infection.

Background: Intestinal microbiota are recognized as an organ with important physiological functions whose alterations have been associated with common diseases including inflammatory intestinal conditions, malnutrition, type-2 diabetes, and cardiovascular diseases. The composition and function of the microbiota in the distal part of the intestine has been mainly described, while there is limited information on the small intestine microbiota. The objective of the present study was to describe the duodenal microbiome in individuals with dyspepsia in the presence or absence of Helicobacter pylori gastric infection.

Irritable bowel syndrome in celiac disease - relationships to celiac disease antibodies and levels of pro-inflammatory cytokines.

Background: Evidence indicates that low-grade inflammation can alter gastrointestinal motor and sensory function and might contribute to the genesis of symptoms in IBS.

Objective: To examine relationships between IBS, disease antibodies and cytokine titers in celiac patients and a control group.

Materials And Methods: IBS, CD activity and serum levels of IL-6, IL-8 and IL12/23p40 were determined in celiac patients and controls.

"It ain't over … till it's over!" Risk-mitigation strategies for patients with gastrointestinal diseases in the aftermath of the COVID-19 pandemic.

The available COVID-19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID-19 pandemic. Local health systems aim to contain the COVID-19 pandemic and hospitals and health-care providers rush to provide the capacity for a surge of COVID-19 patients. However, the short, medium-term, and long-term outcomes of patients with gastrointestinal (GI) diseases without COVID-19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID-19 setting.

Effect of Saccharomyces boulardii CNCM I-745 as complementary treatment of Helicobacter pylori infection on gut microbiome.

Conventional therapy for H. pylori infection includes the combination of antibiotics and a proton-pump inhibitor. Addition of probiotics as adjuvants for H.

Extension for Community Healthcare Outcomes Uruguay: A New Strategy to Promote Best Primary Care Practice for Autism.

. In Uruguay, the special care required for children with neurodevelopmental disorders presents difficulties including lack of access to specialists and rehabilitation services. Project ECHO (Extension for Community Healthcare Outcomes) connects primary care clinicians from remote areas to specialists to enable them to treat complex conditions through ongoing education and mentoring.

A genetically engineered Fc-binding amphiphilic polypeptide for congregating antibodies in vivo.

We report herein an affinity-based hydrogel used in creating subcutaneous depots of antibodies in vivo. The biomaterials design centered on pG_EAK, a polypeptide we designed and expressed in E. coli.

A Comparison of Adjusted Versus Unadjusted Doses of Polymyxin B Based on Renal Function and Incidence of Acute Kidney Injury.

Purpose: To determine whether or not polymyxin B needs dose adjustments based on renal function by comparing the incidence of acute kidney injury (AKI) in patients whose polymyxin B doses were adjusted versus not adjusted according to renal function.

Methods: This was a single-center, prospective study with a retrospective cohort taking place in an acute care community hospital. Forty-two patients treated with polymyxin B were evaluated between April 2012 and December 2015.

Iatrogenic Adrenal Insufficiency Secondary to Combination Therapy with Elvitegravir/Cobicistat/Tenofovir Disoproxil Fumarate/Emtricitabine and Interlaminar Triamcinolone Injection in an AIDS Patient.

We report the first identified case of suspected iatrogenic adrenal insufficiency after an interlaminar injection of triamcinolone acetonide while on concomitant Stribild (elvitegravir 150 mg/cobicistat 150 mg/tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg [EVG/c/TDF/FTC]). A 49-year-old female with HIV on EVG/c/TDF/FTC therapy presented to our endocrinology clinic to be evaluated for suspected Cushing syndrome. Prior to presentation, the patient had been given 2 interlaminar spinal injections of triamcinolone.

Clinical Practice Guideline: Safe Medication Use in the ICU.

Objective: To provide ICU clinicians with evidence-based guidance on safe medication use practices for the critically ill.

Data Sources: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and ISI Web of Science for relevant material to December 2015.

Study Selection: Based on three key components: 1) environment and patients, 2) the medication use process, and 3) the patient safety surveillance system.

Probable Rivaroxaban-Induced Full Body Rash: A Case Report.

Introduction: Rivaroxaban is a novel oral anticoagulant with several indications, one of which is for stroke prevention in nonvalvular atrial fibrillation. We present a case of probable rivaroxaban-induced rash.

Case Summary: A 79-year-old female with a medical history of atrial fibrillation experienced a stroke, after which she was prescribed rivaroxaban 20 mg.