Cx3cr1 controls kidney resident macrophage heterogeneity.

Kidney macrophages are comprised of both monocyte-derived and tissue resident populations; however, the heterogeneity of kidney macrophages and factors that regulate their heterogeneity are poorly understood. Herein, we performed single cell RNA sequencing (scRNAseq), fate mapping, and parabiosis to define the cellular heterogeneity of kidney macrophages in healthy mice. Our data indicate that healthy mouse kidneys contain four major subsets of monocytes and two major subsets of kidney resident macrophages (KRM) including a population with enriched Ccr2 expression, suggesting monocyte origin. Surprisingly, fate mapping data using the newly developed Ms4a3Cre Rosa Stopf/f TdT model indicate that less than 50% of Ccr2+ KRM are derived from Ly6chi monocytes. Instead, we find that Ccr2 expression in KRM reflects their spatial distribution as this cell population is almost exclusively found in the kidney cortex. We also identified Cx3cr1 as a gene that governs cortex specific accumulation of Ccr2+ KRM and show that loss of Ccr2+ KRM reduces the severity of cystic kidney disease in a mouse model where cysts are mainly localized to the kidney cortex. Collectively, our data indicate that Cx3cr1 regulates KRM heterogeneity and niche-specific disease progression.

Fatigue and Syncope Caused by Right Ventricular Perforation by a Pacemaker Lead.

Cardiac devices with intra-ventricular leads are associated with a risk of perforation. This can be a diagnostic challenge given that there is a whole spectrum of clinical presentation from incidental discovery on imaging to large effusions and tamponade. Here we present a case where a patient with permanent pacemaker for complete heart block presented with worsening fatigue that deteriorated to syncopal episodes. Electrocardiogram revealed bradycardia with junctional escape and imaging revealed the tip of the right ventricular lead beyond the ventricular wall. The lead was replaced under fluoroscopic guidance without the need for surgical intervention and the patient was ready for discharge on post-procedure day one. Replacement under fluoroscopic guidance is not only safe, but also enables early discharge, which reduces the burden on health care facilities as well as minimizes the patient's number of days lost in the hospital.

Exploring the impact of the COVID-19 pandemic on provision of cardiology services: a scoping review.

The coronavirus disease-19 (COVID-19) pandemic has forced hospitals to prioritize COVID-19 patients, restrict resources, and cancel all non-urgent elective cardiac procedures. Clinical visits have only been facilitated for emergency purposes. Fewer patients have been admitted to the hospital for both ST-segment elevation myocardial infarctions (STEMI) and non-ST segment elevation myocardial infarctions (NSTEMI) and a profound decrease in heart failure services has been reported. A similar reduction in the patient presentation is seen for ischemic heart disease, decompensated heart failure, and endocarditis. Cardiovascular services, including catheterization, primary percutaneous coronary intervention (PPCI), cardiac investigations such as electrocardiograms (ECGs), exercise tolerance test (ETT), dobutamine stress test, computed tomography (CT) angiography, transesophageal echocardiography (TOE) have been reported to have declined and performed on a priority basis. The long-term implications of this decline have been discussed with major concerns of severe cardiac complications and vulnerabilities in cardiac patients. The pandemic has also had psychological impacts on patients causing them to avoid seeking medical help. This review discusses the effects of the COVID-19 pandemic on the provision of various cardiology services and aims to provide strategies to restore cardiovascular services including structural changes in the hospital to make up for the reduced staff personnel, the use of personal protective equipment in healthcare workers, and provides alternatives for high-risk cardiac imaging, cardiac interventions, and procedures. Implementation of the triage system, risk assessment scores, and telemedicine services in patients and their adaptation to the cardiovascular department have been discussed.

Antimicrobial and antiurease potential of Diorganotin(IV) Schiff bases.

The total phenolic content, flavonoid content, in vitro xanthine oxidase (XOD) inhibitory activity and antioxidant activity (AA) of Eucommia ulmoides Oliver leaf extracts were investigated. The AA investigations included 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, ß-carotene/linoleic acid bleaching assay and oxygen radical absorbance capacity (ORAC) test. The ethyl acetate fraction (EE) showed the highest AA and xanthine oxidase inhibitory activity. Whilst the lowest 50% inhibition (IC50) value of this fraction for DPPH free radical scavenging was 0.045mg/mL, its highest ORAC value was 10.57 µmol TE/mg. The highest inhibition rate against linoleic acid oxidation observed was 69.41%, and the lowest IC50 value for xanthine oxidase activity inhibition was 2.47mg/mL. These results show that E. ulmoides leaf extract is a promising source of natural antioxidants because it contains high contents of bioactive compounds, including chlorogenic acid, rutin, hyperin and astragalin, as detected by high-performance liquid chromatography coupled to HPLC-DAD-ESI-MS.

Zinc supplement in reduction of relapses in children with steroid sensitive nephrotic syndrome.

OBJECTIVE: To determine whether Zinc supplementation could reduce relapse rate in children with nephrotic syndrome. STUDY DESIGN: Randomized-controlled trial. PLACE AND DURATION OF STUDY: National Institute of Child-Health and The Kidney Centre, Karachi, from January 2008 to June 2009. METHODOLOGY: Sixty nephrotic children aged 2 - 15 years were selected. Baseline data including age, number of infections and relapses during pre and post study one year were recorded. Randomization was done to divide into Zinc group (Zg) to receive Zinc versus placebo (Pg) for 6 months. Relapses and infections were treated with standard therapy. T-test and chi-square tests were used to compare the mean values and proportions respectively with significance at p < 0.05. RESULTS: Among 60 children, 54 completed trial (Zg = 25, Pg = 29). Forty (74%) were males and 14 (26%) females. Mean age, pre study relapses and Zinc level in the two groups were similar. Overall, infections and relapses were observed in 43 (79.62%) and 17 cases (31.48%) respectively. There was no significant difference in frequency of infections and mean infection rate in Zg (20, 80% and 1.92 ± 1.47) compared to Pg (23, 79.3% and 2 ± 1.53, p = 0.950). Relapses occurred in 7 (28%) in Zg compared to 10 (34%) in Pg which was not significant (p = 0.609). Mean infection and relapse rate per patient per year (PPPY) in Zg was 1.92 ± 1.47and 1.14 ± 0.37 compared to 2 ± 1.53 and1.3 ± 0.48 in Pg respectively (p=0.846, 0.464). Pre study relapses in two groups were similar (Zg vs. Pg = 96 vs. 96.6%) whereas post study relapses in Zg were lower (7, 28%) compared to Pg (10, 34.5%). Post study mean relapse rate in Zg was 1.14 ± 0.37 PPPY compared to 2.71 ± 1.11 in pre study (p = 0.005). In Pg, post study mean relapse rate PPPY was 1.30 ± 0.48 compared to 1.70 ± 0.48 in pre study period (p = 0.037). Relapse rate reduction was 43% after Zinc supplementation compared to 27% reduction in placebo. Metallic taste was observed in 10% of cases. CONCLUSION: Zinc supplementation was helpful in reducing relapses in nephrotic syndrome.