New insights into the molecular regulation of kidney disease: contributions of APOL1 and MYH9

People of African ancestry (AA) are at greater risk of developing chronic kidney disease than those of non-AA. Much of this risk has been linked to specific genetic haplotypes on chromosome 22, near the genes APOL1, encoding apolipoprotein L1, and MYH9, encoding non-muscle myosin heavy chain IIA (NMHCIIA). The mechanisms by which the disease-associated chromosome 22 haplotypes promote kidney damage are unknown. Apolipoprotein L1 is a circulating protein with no known role in kidney function. However, the kidney disease-associated chromosome 22 haplotypes are protective against trypanosome infection, resulting in positive selective pressure for these haplotypes in western Africa, where trypanosome infection is endemic. In contrast, NMHCIIA may have an important role in glomerular function, and mutations in MYH9 are associated with glomerular disease, yet the disease-associated chromosome 22 haplotypes do not involve coding sequence variations in MYH9. With no clear disease-causing role for genes near the chromosome 22 risk locus, it is plausible that indirect mechanisms of gene regulation may be responsible for the increased disease risk. This study examines several potential pathways for kidney injury, including altered glomerular gene expression in carriers of chromosome 22 risk haplotypes, and the role of altered expression of MYH9 in podocyte cell biology and kidney disease. We found that carriers of chromosome 22 risk variants exhibited differential glomerular gene expression in pathways promoting kidney injury. We also found decreased glomerular NMHCIIA expression in human FSGS kidney biopsies, and altered cell structure and mechanical function when Myh9 is ablated in murine podocytes. Further, Myh9 podocyte deletion predisposed mice to glomerulopathy in response to injury by the DOCA-salt uninephrectomy model of hypertension. Taken together, these findings demonstrate direct and indirect effects of chromosome 22 risk variants on glomerular gene expression which promote kidney injury

Malaria perception among pregnant women in Chhattisgarh, India

BACKGROUND: Malaria in pregnant women continues to be a public health problem in India. The prevalence of malaria in pregnancy is particularly high in the tribal conflict areas of India such as Chhattisgarh. Pregnant women have less acquired immunity protecting them against malaria than non-pregnant women of child bearing age. The decreased immunity results in a much more severe presentation of malaria symptoms, and potential death of both mother and fetus during malaria in pregnancy. Recognizing the need for effective malaria interventions in pregnant women, global and national malaria prevention and treatment guidelines have been established. Practice of these guidelines has been found to be inadequate in the Asian Pacific Region. LITERATURE REVIEW FINDINGS: Qualitative studies on the knowledge, attitudes and practices of malaria interventions have demonstrated that meeting communities at their level of understanding is essential in circumventing malaria spread. In an effort to create a synergy between health care workers, national and global malaria control strategies and pregnant women, there is the need to identify pregnant women’s knowledge, attitudes and practices of malaria interventions. Currently, there is no data on the knowledge, attitudes and practices of pregnant women in the conflict districts of Chhattisgarh, India, where malaria prevalence and related symptoms have been identified to be significantly high. PROPOSED PROJECT: This study seeks to assess the knowledge, attitudes and practices of malaria prevention and treatment in pregnant women in the conflict areas of Chhattisgarh, India, using a cross-sectional qualitative research design. This study will highlight the understanding of malaria transmission, perceptions of cause, recognition of signs and symptoms, treatment-seeking behaviors, preventive measures and practices of pregnant women who visit the antenatal clinic and those who do not. CONCLUSION: If this study demonstrates knowledge and attitudes that favor customary or unproven methods of malaria interventions as shown in previous studies, then this may explain the present rate of MIP in these districts and hence the need for specific mediations for controlling and preventing malaria in this populace. SIGNIFICANCE: Findings from this study will help inform malaria education programs, health policies and practices that are tailored or targeted towards pregnant women in Chhattisgarh, India

New Insights into Glomerular Parietal Epithelial Cell Activation and Its Signaling Pathways in Glomerular Diseases

The glomerular parietal epithelial cells (PECs) have aroused an increasing attention recently. The proliferation of PECs is the main feature of crescentic glomerulonephritis; besides that, in the past decade, PEC activation has been identified in several types of noninflammatory glomerulonephropathies, such as focal segmental glomerulosclerosis, diabetic glomerulopathy, and membranous nephropathy. The pathogenesis of PEC activation is poorly understood; however, a few studies delicately elucidate the potential mechanisms and signaling pathways implicated in these processes. In this review we will focus on the latest observations and concepts about PEC activation in glomerular diseases and the newest identified signaling pathways in PEC activation

Perivascular Gli1+ Progenitors Are Key Contributors to Injury-Induced Organ Fibrosis

SummaryMesenchymal stem cells (MSCs) reside in the perivascular niche of many organs, including kidney, lung, liver, and heart, although their roles in these tissues are poorly understood. Here, we demonstrate that Gli1 marks perivascular MSC-like cells that substantially contribute to organ fibrosis. In vitro, Gli1+ cells express typical MSC markers, exhibit trilineage differentiation capacity, and possess colony-forming activity, despite constituting a small fraction of the platelet-derived growth factor-β (PDGFRβ)+ cell population. Genetic lineage tracing analysis demonstrates that tissue-resident, but not circulating, Gli1+ cells proliferate after kidney, lung, liver, or heart injury to generate myofibroblasts. Genetic ablation of these cells substantially ameliorates kidney and heart fibrosis and preserves ejection fraction in a model of induced heart failure. These findings implicate perivascular Gli1+ MSC-like cells as a major cellular origin of organ fibrosis and demonstrate that these cells may be a relevant therapeutic target to prevent solid organ dysfunction after injury

Evaluation of Mental Disorders Using Proton Magnetic Resonance Spectroscopy in Dialysis and Predialysis Patients

Background/Aims: Psychological complications are prevalent in patients with chronic kidney disease (CKD). This study aimed to investigate mental disorders in stage 4-5 CKD patients, to detect metabolite concentrations in the brain by proton magnetic resonance spectroscopy (1H-MRS) and to compare the effects of different dialysis therapies on mental disorders in end-stage renal disease (ESRD). Methods: The sample population was made up of predialysis (13), hemodialysis (HD) (13), and peritoneal dialysis (PD) patients (12). We collected the baseline data of patients’ age, sex, hemoglobin (Hb) and parathyroid hormone（PTH） levels. The predialysis patients served as the control group. The psychological status of the three groups was assessed using three psychological scales. 1H-MRS was used to evaluate the relative metabolite concentrations in the bilateral amygdala, hippocampus and unilateral anterior cingulated cortex (ACC). Results: The psychological status was better in HD patients than in predialysis and PD patients. 1H-MRS alterations were predominantly found in the ACC. Choline-containing compounds relative to creatine (Cho/Cr), myo-inositol relative to creatine (MI/Cr) and glutamate and glutamine relative to creatine (Glx/Cr) in the ACC were higher in HD patients. 1H-MRS results were correlated with the baseline data and the scores of psychological scales. Conclusions: CKD patients showed different types of mental disorders as well as metabolite disturbances in the brain. The metabolite concentrations correlated with the psychological status which was better in HD than in predialytic and PD patients

Prevention and treatment of malaria in pregnancy: what do pregnant women and health care workers in East India know and do about it?

Background: Limited qualitative research has been performed in India to investigate views and behaviours of pregnant women regarding malaria despite the threat of malaria-related adverse maternal and neonatal outcomes. To address this gap, a comprehensive study on malaria prevention and treatment attitudes, knowledge and behaviour among pregnant women in India was conducted. Methods: Pregnant women and healthcare workers (HCWs), encompassing clinic-based providers, traditional birth attendants, and auxiliary nurse-midwives were enrolled for in-depth interviews (IDIs) at 7 hospital sites and nearby communities in Jharkhand and Chhattisgarh States. Questions addressed health concerns and attitudes, knowledge and practices regarding malaria prevention and treatment; probing covered modern and traditional approaches. Data were analyzed using a thematic approach. Results: A total of 83 pregnant women and 119 HCWs participated in 202 IDIs, 90 in Jharkhand and 112 in Chhattisgarh. A majority of Jharkhand respondents, but only one-fourth in Chhattisgarh, named malaria among top health issues for pregnant women. Just over half of pregnant women were willing to try new prevention methods (especially insecticide-treated bed nets), although cost-related barriers to such methods were stressed. Most respondents voiced concerns about malaria treatment during pregnancy, mainly citing potential harm to the baby. Most knew that mosquitoes transmitted malaria, but a substantial minority, including among HCWs, described incorrect transmission modes. Most knew a proven prevention method (usually bed nets or coils); a few knew other methods. A minority of pregnant women, but most HCWs, knew about malaria treatment, although some HCWs described unproven treatments. Most respondents described use of modern prevention methods in their communities, typically bed nets, although probing revealed irregular use. Half (especially in Jharkhand and particularly HCWs) described use of traditional prevention approaches such as burning leaves and rubbing oils on the body; traditional remedies for malaria treatment were common, and varied by site and population. Conclusions: Understanding of malaria varied as a concern for pregnant women, continued use of unproven malaria prevention and treatment strategies was evident in this population in India. These results highlight the need to educate both pregnant women and HCWs about effective malaria methods to protect pregnant women and their babies from malaria