Influence of hyaluronic acid on intra-articular friction - a biomechanical study in whole animal joints.

Background: Cartilage is a mechanically highly stressed tissue in the human body and an important part of synovial joints. The joint cartilage is lubricated by synovial fluid with hyaluronic acid (HA) as main component. However, in joints with osteoarthritis HA has a lower concentration and molecular weight compared to healthy joints.

Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination.

Background: National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures.

Methods: Samples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode.

A targeted amplicon sequencing panel to simultaneously identify mosquito species and Plasmodium presence across the entire Anopheles genus.

Anopheles is a diverse genus of mosquitoes comprising over 500 described species, including all known human malaria vectors. While a limited number of key vector species have been studied in detail, the goal of malaria elimination calls for surveillance of all potential vector species. Here, we develop a multilocus amplicon sequencing approach that targets 62 highly variable loci in the Anopheles genome and two conserved loci in the Plasmodium mitochondrion, simultaneously revealing both the mosquito species and whether that mosquito carries malaria parasites.

Ambulatory noninsulin treatment of type 2 diabetes mellitus in the United States, 2015 to 2019.

Objective: To examine trends in the noninsulin drug treatment of type 2 diabetes, including first- and second-line therapies on top of metformin, from 2015 to 2019.

Participants And Methods: We conducted a descriptive analysis of cross-sectional data using the IQVIA National Disease and Therapeutic Index, a nationally representative audit of ambulatory physician practices in the United States. We focused on the use of noninsulin pharmacological treatments for type 2 diabetes among individuals aged 35 years and older between January 1, 2015 and December 31, 2019.

Temporal evolution of sulfadoxine-pyrimethamine resistance genotypes and genetic diversity in response to a decade of increased interventions against Plasmodium falciparum in northern Ghana.

Background: Anti-malarial drug resistance remains a key concern for the global fight against malaria. In Ghana sulfadoxine-pyrimethamine (SP) is used for intermittent preventive treatment of malaria in pregnancy and combined with amodiaquine for Seasonal Malaria Chemoprevention (SMC) during the high malaria season. Thus, surveillance of molecular markers of SP resistance is important to guide decision-making for these interventions in Ghana.

Multi-locus genotyping reveals established endemicity of a geographically distinct Plasmodium vivax population in Mauritania, West Africa.

Background: Plasmodium vivax has been recently discovered as a significant cause of malaria in Mauritania, although very rare elsewhere in West Africa. It has not been known if this is a recently introduced or locally remnant parasite population, nor whether the genetic structure reflects epidemic or endemic transmission.

Methodology/principal Findings: To investigate the P.

Development of copy number assays for detection and surveillance of piperaquine resistance associated plasmepsin 2/3 copy number variation in Plasmodium falciparum.

Background: Long regarded as an epicenter of drug-resistant malaria, Southeast Asia continues to provide new challenges to the control of Plasmodium falciparum malaria. Recently, resistance to the artemisinin combination therapy partner drug piperaquine has been observed in multiple locations across Southeast Asia. Genetic studies have identified single nucleotide polymorphisms as well as copy number variations in the plasmepsin 2 and plasmepsin 3 genes, which encode haemoglobin-degrading proteases that associate with clinical and in vitro piperaquine resistance.

Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial.

Background: Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance.

Methods: In this multicentre, open-label, randomised trial, we recruited patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries.

Microarray analyses reveal strain-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 variants following natural infection and vaccination.

Vaccines based on Plasmodium falciparum apical membrane antigen 1 (AMA1) have failed due to extensive polymorphism in AMA1. To assess the strain-specificity of antibody responses to malaria infection and AMA1 vaccination, we designed protein and peptide microarrays representing hundreds of unique AMA1 variants. Following clinical malaria episodes, children had short-lived, sequence-independent increases in average whole-protein seroreactivity, as well as strain-specific responses to peptides representing diverse epitopes.

Effect of graft positioning on dissipated energy in knee osteochondral autologous transplantation-A biomechanical study.

Focal cartilage defects can be treated by osteochondral autologous transplantation (OAT). High congruence of the graft with the surrounding cartilage structure is essential for a good clinical outcome, but can not always be achieved. We recently established a method to measure dissipated energy (DE) as a friction parameter in knee joints.

Influence of reduction accuracy in lateral tibial plateau fractures on intra-articular friction - a biomechanical study.

Background: Lateral tibial split fractures (LTSF) usually require surgical therapy with screw or plate osteosynthesis. Excellent anatomical reduction of the fracture is thereby essential to avoid post-traumatic osteoarthritis. In clinical practice, a gap and step of 2 mm have been propagated as maximum tolerable limit.

Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study.

Background: The emergence and spread of resistance in Plasmodium falciparum malaria to artemisinin combination therapies in the Greater Mekong subregion poses a major threat to malaria control and elimination. The current study is part of a multi-country, open-label, randomised clinical trial (TRACII, 2015-18) evaluating the efficacy, safety, and tolerability of triple artemisinin combination therapies. A very high rate of treatment failure after treatment with dihydroartemisinin-piperaquine was observed in Thailand, Cambodia, and Vietnam.

Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study.

Background: A multidrug-resistant co-lineage of Plasmodium falciparum malaria, named KEL1/PLA1, spread across Cambodia in 2008-13, causing high rates of treatment failure with the frontline combination therapy dihydroartemisinin-piperaquine. Here, we report on the evolution and spread of KEL1/PLA1 in subsequent years.

Methods: For this genomic epidemiology study, we analysed whole genome sequencing data from P falciparum clinical samples collected from patients with malaria between 2007 and 2018 from Cambodia, Laos, northeastern Thailand, and Vietnam, through the MalariaGEN P falciparum Community Project.

Genomic structure and diversity of Plasmodium falciparum in Southeast Asia reveal recent parasite migration patterns.

Estimates of Plasmodium falciparum migration may inform strategies for malaria elimination. Here we elucidate fine-scale parasite population structure and infer recent migration across Southeast Asia using identity-by-descent (IBD) approaches based on genome-wide single nucleotide polymorphisms called in 1722 samples from 54 districts. IBD estimates are consistent with isolation-by-distance.

Mapping imported malaria in Bangladesh using parasite genetic and human mobility data.

For countries aiming for malaria elimination, travel of infected individuals between endemic areas undermines local interventions. Quantifying parasite importation has therefore become a priority for national control programs. We analyzed epidemiological surveillance data, travel surveys, parasite genetic data, and anonymized mobile phone data to measure the spatial spread of malaria parasites in southeast Bangladesh.

Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets.

Variant surface antigens (VSAs) play a critical role in severe malaria pathogenesis. Defining gaps, or "lacunae", in immunity to these Plasmodium falciparum antigens in children with severe malaria would improve our understanding of vulnerability to severe malaria and how protective immunity develops. Using a protein microarray with 179 antigen variants from three VSA families as well as more than 300 variants of three other blood stage P.

Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study.

Background: Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs critical to elimination efforts. Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon.

Methods: Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional surveys from May 2013 to March 2014 along the slope of mount Cameroon.

Community Health Warriors: Marshallese Community Health Workers' Perceptions and Experiences with CBPR and Community Engagement.

Our manuscript highlights the viewpoints and reflections of the native Marshallese community health workers (CHWs) engaged in research with the local Marshallese community in Northwest Arkansas. In particular, this paper documents the vital role Marshallese CHWs play in the success of programs and research efforts. The negative health effects of nuclear testing in the Marshall Islands has been passed down through many generations, along with unfavorable attitudes toward the U.

Association of a Novel Mutation in the Plasmodium falciparum Chloroquine Resistance Transporter With Decreased Piperaquine Sensitivity.

Background: Amplified copy number in the plasmepsin II/III genes within Plasmodium falciparum has been associated with decreased sensitivity to piperaquine. To examine this association and test whether additional loci might also contribute, we performed a genome-wide association study of ex vivo P. falciparum susceptibility to piperaquine.

Parasite dynamics in the peripheral blood and the placenta during pregnancy-associated malaria infection.

Background: Malaria infections during pregnancy lead to sequestration of parasite infected red blood cells in the placenta. Placental infection can result in adverse outcomes for mothers and infants. Despite many studies, it remains unclear which peripheral blood infections during pregnancy lead to development of placental malaria.

Interpretive policy analysis: Marshallese COFA migrants and the Affordable Care Act.

Background: Since the enactment of the Affordable Care Act (ACA), the rate of uninsured in the United States has declined significantly. However, not all legal residents have benefited equally. As part of a community-based participatory research (CBPR) partnership with the Marshallese community, an interpretative policy analysis research project was conducted to document Marshallese Compact of Free Association (COFA) migrants' understanding and experiences regarding the ACA and related health policies.

Hemoglobin C Trait Provides Protection From Clinical Falciparum Malaria in Malian Children.

Background: Hemoglobin C trait, like hemoglobin S trait, protects against severe malaria in children, but it is unclear whether hemoglobin C trait also protects against uncomplicated malaria. We hypothesized that Malian children with hemoglobin C trait would have a lower risk of clinical malaria than children with hemoglobin AA.

Methods: Three hundred children aged 0-6 years were enrolled in a cohort study of malaria incidence in Bandiagara, Mali, with continuous passive and monthly active follow-up from June 2009 to June 2010.

Ex Vivo Drug Susceptibility Testing and Molecular Profiling of Clinical Plasmodium falciparum Isolates from Cambodia from 2008 to 2013 Suggest Emerging Piperaquine Resistance.

Cambodia's first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistant Plasmodium falciparum malaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying for ex vivo drug susceptibility and molecular drug resistance markers to guide the selection of an effective alternative to DHA-PPQ. Over the last 3 study years, PPQ susceptibility declined dramatically (geomean 50% inhibitory concentration [IC50] increased from 12.