The global and national burden of chronic kidney disease attributable to ambient fine particulate matter air pollution: a modelling study.

Introduction: We aimed to integrate all available epidemiological evidence to characterise an exposure-response model of ambient fine particulate matter (PM) and the risk of chronic kidney disease (CKD) across the spectrum of PM concentrations experienced by humans. We then estimated the global and national burden of CKD attributable to PM.

Methods: We collected data from prior studies on the association of PM with CKD and used an integrative meta-regression approach to build non-linear exposure-response models of the risk of CKD associated with PM exposure.

Convergent Pathways in Idiopathic Autism Revealed by Time Course Transcriptomic Analysis of Patient-Derived Neurons.

Potentially pathogenic alterations have been identified in individuals with autism spectrum disorders (ASDs) within a variety of key neurodevelopment genes. While this hints at a common ASD molecular etiology, gaps persist in our understanding of the neurodevelopmental mechanisms impacted by genetic variants enriched in ASD patients. Induced pluripotent stem cells (iPSCs) can model neurodevelopment in vitro, permitting the characterization of pathogenic mechanisms that manifest during corticogenesis.

Prevalence of Asymptomatic Parasitemia and Gametocytemia in HIV-Infected Children on Differing Antiretroviral Therapy.

Laboratory data and prior pediatric reports indicate that HIV protease inhibitor (PI)-based antiretroviral therapy (ARV) kills gametocytes and reduces rates of gametocytemia, but not asymptomatic parasitemia, in a high malaria-transmission area. To determine whether ARV regimen impacts these rates in areas with less-intense malaria transmission, we compared asymptomatic parasitemia and gametocytemia rates in HIV-infected children by ARV regimen in Lilongwe, Malawi, an area of low-to-moderate transmission intensity. HIV PI lopinavir-ritonavir (LPV-rtv) ARV- or non-nucleoside reverse transcriptase inhibitor nevirapine ARV-treated children did not differ in the rates of polymerase chain reaction-detected asymptomatic parasitemia (relative risk [RR] 0.

PeakCaller: an automated graphical interface for the quantification of intracellular calcium obtained by high-content screening.

Background: Intracellular calcium is an important ion involved in the regulation and modulation of many neuronal functions. From regulating cell cycle and proliferation to initiating signaling cascades and regulating presynaptic neurotransmitter release, the concentration and timing of calcium activity governs the function and fate of neurons. Changes in calcium transients can be used in high-throughput screening applications as a basic measure of neuronal maturity, especially in developing or immature neuronal cultures derived from stem cells.

Patient-derived hiPSC neurons with heterozygous CNTNAP2 deletions display altered neuronal gene expression and network activity.

Variants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We previously reprogrammed fibroblasts from a family trio consisting of two carriers of heterozygous intragenic CNTNAP2 deletions into human induced pluripotent stem cells (hiPSCs) and described decreased migration in the neural progenitor cells (NPCs) differentiated from the affected CNTNAP2 carrier in this trio. Here, we report the effect of this heterozygous intragenic deletion in CNTNAP2 on global gene expression and neuronal activity in the same cohort.

The effect of local variation in malaria transmission on the prevalence of sulfadoxine-pyrimethamine resistant haplotypes and selective sweep characteristics in Malawi.

Background: Persistence of sulfadoxine-pyrimethamine (SP) resistance has been described in an urban setting in Malawi where malaria transmission is relatively low. Higher malaria transmission is associated with greater genetic diversity and more frequent genetic recombination, which could lead to a more rapid re-emergence of SP-sensitive parasites, as well as more rapid degradation of selective sweeps. In this study, the impact of local variation in malaria transmission on the prevalence of SP-resistant haplotypes and selective sweep characteristics was investigated at an urban site with low parasite prevalence and two rural sites with moderate and high parasite prevalence.

Human Inducible Pluripotent Stem Cells and Autism Spectrum Disorder: Emerging Technologies.

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental condition. Symptoms of ASD cover the spectrum from mild qualitative differences in social interaction to severe communication and social and behavioral challenges that require lifelong support. Attempts at understanding the pathophysiology of ASD have been hampered by a multifactorial etiology that stretches the limits of current behavioral and cell based models.

Persistence of Sulfadoxine-Pyrimethamine Resistance Despite Reduction of Drug Pressure in Malawi.

Background: In 2007, Malawi replaced sulfadoxine-pyrimethamine (SP) with an artemisinin-based combination therapy as the first-line treatment for uncomplicated Plasmodium falciparum malaria in response to failing SP efficacy. Here we estimate the effect of reduced SP pressure on the prevalence of SP-resistant parasites and the characteristics of the associated selective sweeps flanking the resistance loci.

Methods: Samples obtained from individuals with clinical malaria during a period of high SP use (1999-2001), a transitional period (2007-2008), and a period of low SP use (2012) were genotyped for resistance markers at pfdhfr-ts codons 51, 59, and 108 and pfdhps codons 437, 540, and 581.

A comprehensive survey of polymorphisms conferring anti-malarial resistance in Plasmodium falciparum across Pakistan.

Background: Few studies have been conducted in Pakistan to determine the efficacy of chloroquine and sulphadoxine-pyrimethamine (SP), which remain in use as treatment for Plasmodium vivax and in combination with artesunate to treat Plasmodium falciparum, respectively. In this study, samples from several sites across Pakistan were characterized to determine prevalence of molecular resistance markers in the P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes and the origin of chloroquine-resistant P.

Enhanced motility of a Proteus mirabilis strain expressing hybrid FlaAB flagella.

Proteus mirabilis has two tandemly arranged flagellin-encoding genes, flaA and flaB. flaA is transcribed from a sigma(28) promoter, while flaB is silent. flaA and flaB can undergo reversible rearrangement to produce a set of hybrid genes referred to as flaAB.