A Patient Case of Malan Syndrome Involving 19p13.2 Deletion of with Longitudinal Follow-Up and Future Prospectives.

Malan syndrome is a rare overgrowth syndrome resulting from haploinsufficiency due to heterozygous loss-of-function mutations or microdeletions of on chromosome 19 at p13.2. Phenotypic presentation can vary but is characterized by macrocephaly, long and slender body habitus, skeletal abnormalities, and intellectual disability.

Down syndrome and DYRK1A overexpression: relationships and future therapeutic directions.

Down syndrome is a genetic-based disorder that results from the triplication of chromosome 21, leading to an overexpression of many triplicated genes, including the gene encoding Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A). This protein has been observed to regulate numerous cellular processes, including cell proliferation, cell functioning, differentiation, and apoptosis. Consequently, an overexpression of has been reported to result in cognitive impairment, a key phenotype of individuals with Down syndrome.

Empirical modeling of agricultural climate risk.

Effective policies for adaptation to climate change require understanding how impacts are related to exposures and vulnerability, the dimensions of the climate system that will change most and where human impacts will be most draconian, and the institutions best suited to respond. Here, we propose a simple method for more credibly pairing empirical statistical damage estimates derived from recent weather and outcome observations with projected future climate changes and proposed responses. We first analyze agricultural production and loan repayment data from Brazil to understand vulnerability to historical variation in the more predictable components of temperature and rainfall (trend and seasonality) as well as to shocks (both local and over larger spatial scales).

Induced alternative splicing an opportunity to study PCSK9 protein isoforms at physiologically relevant concentrations.

Splice modulating antisense oligomers (AOs) are increasingly used to modulate RNA processing. While most are investigated for their use as therapeutics, AOs can also be used for basic research. This study examined their use to investigate internally and terminally truncated proprotein convertase subtilisin/kexin type 9 (PCSK9) protein isoforms.

Economic vulnerability, violence, and sexual risk factors for HIV among female sex workers in Tijuana, Mexico.

Economic vulnerability is often reported to underlie involvement in sex work among female sex workers (FSW), but may also create urgency in women's work, limiting women's negotiating power with clients and in turn, increasing their vulnerability for violence and HIV. This study assessed economic vulnerability in relation to violence and sexual risk behaviors for HIV among a sample of FSW in Tijuana, Mexico. FSW at least 18 years of age were recruited through venue-based sampling for a survey (n = 228) and in-depth interviews (n = 50) to investigate HIV risk factors in this region.

Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies.

Polyglutamine (polyQ) ataxias are a heterogenous group of neurological disorders all caused by an expanded CAG trinucleotide repeat located in the coding region of each unique causative gene. To date, polyQ ataxias encompass six disorders: spinocerebellar ataxia types 1, 2, 3, 6, 7, and 17 and account for a larger group of disorders simply known as polyglutamine disorders, which also includes Huntington's disease. These diseases are typically characterised by progressive ataxia, speech and swallowing difficulties, lack of coordination and gait, and are unfortunately fatal in nature, with the exception of SCA6.

Splice correction therapies for familial hypercholesterolemic patients with low-density lipoprotein receptor mutations.

Purpose Of Review: Antisense oligomers (ASOs) have been available for decades: however, only recently have these molecules been applied clinically. This review aims to discuss the possible development of antisense-mediated splice correction therapies as precision medicines for familial hypercholesterolemic patients carrying mutations that compromise normal splicing of the low-density lipoprotein receptor (LDLR) gene transcript.

Recent Findings: Three antisense drugs are currently being assessed in ongoing clinical trials for dyslipidemias, aiming to lower the plasma concentrations of lipoproteins that lead to end-organ damage, principally coronary artery disease.

Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides.

Antisense oligomers (AOs) are increasingly being used to modulate RNA splicing in live cells, both for research and for the development of therapeutics. While the most common intended effect of these AOs is to induce skipping of whole exons, rare examples are emerging of AOs that induce skipping of only part of an exon, through activation of an internal cryptic splice site. In this report, we examined seven AO-induced cryptic splice sites in six genes.

Neurodegenerative diseases: a hotbed for splicing defects and the potential therapies.

Precursor messenger RNA (pre-mRNA) splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions (introns) and ligates coding regions (exons) into a continuous message (mature mRNA). This process is highly regulated and can be highly flexible through a process known as alternative splicing, which allows for several transcripts to arise from a single gene, thereby greatly increasing genetic plasticity and the diversity of proteome. Alternative splicing is particularly prevalent in neuronal cells, where the splicing patterns are continuously changing to maintain cellular homeostasis and promote neurogenesis, migration and synaptic function.

Cost and cost-effectiveness of a real-world HCV treatment program among HIV-infected individuals in Myanmar.

Introduction: Over half of those hepatitis C virus (HCV)/HIV coinfected live in low-income and middle-income countries, and many remain undiagnosed or untreated. In 2016, Médecins Sans Frontières (MSF) established a direct-acting antiviral (DAA) treatment programme for people HCV/HIV coinfected in Myanmar. The purpose of our study was to evaluate the real-world cost and cost-effectiveness of this programme, and potential cost-effectiveness if implemented by the Ministry of Health (MoH).

Cost-effectiveness of hepatitis C virus (HCV) elimination strategies among people who inject drugs (PWID) in Tijuana, Mexico.

Background And Aims: In Latin America, Mexico was first to launch a hepatitis C virus (HCV) elimination strategy, where people who inject drugs (PWID) are a main risk group for transmission. In Tijuana, HCV seroprevalence among PWID is > 90%, with minimal harm reduction (HR). We evaluated cost-effectiveness of strategies to achieve the incidence elimination target among PWID in Tijuana.

Removal of the Polyglutamine Repeat of Ataxin-3 by Redirecting pre-mRNA Processing.

Spinocerebellar ataxia type 3 (SCA3) is a devastating neurodegenerative disease for which there is currently no cure, nor effective treatment strategy. One of nine polyglutamine disorders known to date, SCA3 is clinically heterogeneous and the main feature is progressive ataxia, which in turn affects speech, balance and gait of the affected individual. SCA3 is caused by an expanded polyglutamine tract in the ataxin-3 protein, resulting in conformational changes that lead to toxic gain of function.

In Vitro Validation of Phosphorodiamidate Morpholino Oligomers.

One of the crucial aspects of screening antisense oligonucleotides destined for therapeutic application is confidence that the antisense oligomer is delivered efficiently into cultured cells. Efficient delivery is particularly vital for antisense phosphorodiamidate morpholino oligomers, which have a neutral backbone, and are known to show poor gymnotic uptake. Here, we report several methods to deliver these oligomers into cultured cells.

Voter information campaigns and political accountability: Cumulative findings from a preregistered meta-analysis of coordinated trials.

Voters may be unable to hold politicians to account if they lack basic information about their representatives' performance. Civil society groups and international donors therefore advocate using voter information campaigns to improve democratic accountability. Yet, are these campaigns effective? Limited replication, measurement heterogeneity, and publication biases may undermine the reliability of published research.

A comparison of carcass decomposition and associated insect succession onto burnt and unburnt pig carcasses.

The rate of decomposition and insect succession onto decomposing pig carcasses were investigated following burning of carcasses. Ten pig carcasses (40-45 kg) were exposed to insect activity during autumn (March-April) in Western Australia. Five replicates were burnt to a degree described by the Crow-Glassman Scale (CGS) level #2, while five carcasses were left unburnt as controls.

The heterogeneous effects of HIV testing.

An extensive multi-disciplinary literature examines the effects of learning one's HIV status on subsequent risky sexual behaviors. However, many of these studies rely on non-experimental designs; use self-reported outcome measures; or both. In this study, we investigate the effects of a randomly assigned home based HIV testing and counseling (HTC) intervention on risky sexual behaviors and schooling investments among school-age females in Malawi.

Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial.

Background: Lack of education and an economic dependence on men are often suggested as important risk factors for HIV infection in women. We assessed the efficacy of a cash transfer programme to reduce the risk of sexually transmitted infections in young women.

Methods: In this cluster randomised trial, never-married women aged 13-22 years were recruited from 176 enumeration areas in the Zomba district of Malawi and randomly assigned with computer-generated random numbers by enumeration area (1:1) to receive cash payments (intervention group) or nothing (control group).

The short-term impacts of a schooling conditional cash transfer program on the sexual behavior of young women.

Recent evidence suggests that conditional cash transfer (CCT) programs for schooling are effective in raising school enrollment and attendance. However, there is also reason to believe that such programs can affect other outcomes, such as the sexual behavior of their young beneficiaries. Zomba Cash Transfer Program is a randomized ongoing CCT intervention targeting young women in Malawi that provides incentives (in the form of school fees and cash transfers) to current schoolgirls and recent dropouts to stay in or return to school.