Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide.

Objectives: We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory.

Methods: Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology.

Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide.

Methods/findings: In our ongoing USA feasibility/efficacy clinical trial, data collated with other ongoing and earlier published results proved high performance of an Immunochromatographic-test(ICT) that enables accurate, rapid diagnosis/treatment, establishing new paradigms for care. Overall results from patient blood and/or serum samples tested with ICT compared with gold-standard-predicate-test results found ICT performance for 4606 sera/1876 blood, 99.

Evaluation of the acceptability of point of care diagnostic test for prenatal toxoplasmosis (translational research phase III).

Background: A new point of care test (POC) was developed that is promising as a tool to enhance impact of prenatal care programs for toxoplasmosis, however, no reports exist about its use or acceptability for healthcare personnel and mothers in Colombia.

Methods: This was a translational research - phase III study of the acceptability of a new POC test (Toxoplasma ICT IgG-IgM, LDBio) for qualitative diagnosis of toxoplasmosis in 783 pregnant women and 30 health personnel in primary health care sites in the city of Armenia, Quindío (Colombia). Along with collection of the results of diagnostic POC and confirmatory test and demographic information, we evaluated acceptability through measure of the willingness, credibility, and satisfaction by using questionnaires with a Likert scale during routine prenatal care visits.

Fishers' multidimensional knowledge advances fisheries and aquatic science.

Fishers' Indigenous and local knowledge (ILK) has multidimensional contributions to improve fisheries and aquatic ecosystems science, ranging from algae to whales and including management, conservation, ecology, and impact assessment. The challenges are to sustain this knowledge, recognize its value, and to include ILK holders in resource management and decision-making.

Effects of interactions between anthropogenic stressors and recurring perturbations on ecosystem resilience and collapse.

Insights into declines in ecosystem resilience and their causes and effects can inform preemptive action to avoid ecosystem collapse and loss of biodiversity, ecosystem services, and human well-being. Empirical studies of ecosystem collapse are rare and hampered by ecosystem complexity, nonlinear and lagged responses, and interactions across scales. We investigated how an anthropogenic stressor could diminish ecosystem resilience to a recurring perturbation by altering a critical ecosystem driver.

ACGME Milestones in global health: Need for standardized assessment of global health training in obstetrics/gynecology residency.

Collective interest in global health training during US obstetrics/gynecology (Ob/Gyn) residency has grown over the past decade. The benefits of participation in global health electives have been well described. This review seeks to determine what literature exists regarding the use of Accreditation Council for Graduate Medical Education (ACGME) Milestones in Ob/Gyn residency as an assessment tool to evaluate global health programs.

The Downstream Impacts of Hydropower Dams and Indigenous and Local Knowledge: Examples from the Peace-Athabasca, Mekong, and Amazon.

There has been much written about the negative social and environmental impacts of large hydropower dams, particularly the impacts on people and the environment caused by flooding linked to the creation of large reservoirs. There has also long been recognition of the importance of Indigenous and local knowledge for understanding ecological processes and environmental impacts. In this paper, however, we focus on a topic that has received insufficient consideration: the downstream impacts of dams, and the role of Indigenous and local knowledge in assessing and addressing these impacts.

Design of substituted imidazolidinylpiperidinylbenzoic acids as chemokine receptor 5 antagonists: potent inhibitors of R5 HIV-1 replication.

The redesign of the previously reported thiophene-3-yl-methyl urea series, as a result of potential cardiotoxicity, was successfully accomplished, resulting in the identification of a novel potent series of CCR5 antagonists containing the imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate hERG inhibition. The structure-activity relationship (SAR) that was developed was used to identify compounds with the best pharmacological profile to inhibit HIV-1.

Mitigating hERG Inhibition: Design of Orally Bioavailable CCR5 Antagonists as Potent Inhibitors of R5 HIV-1 Replication.

A series of CCR5 antagonists representing the thiophene-3-yl-methyl ureas were designed that met the pharmacological criteria for HIV-1 inhibition and mitigated a human ether-a-go-go related gene (hERG) inhibition liability. Reducing lipophilicity was the main design criteria used to identify compounds that did not inhibit the hERG channel, but subtle structural modifications were also important. Interestingly, within this series, compounds with low hERG inhibition prolonged the action potential duration (APD) in dog Purkinje fibers, suggesting a mixed effect on cardiac ion channels.

Design and synthesis of pyridin-2-ylmethylaminopiperidin-1-ylbutyl amide CCR5 antagonists that are potent inhibitors of M-tropic (R5) HIV-1 replication.

A series of CCR5 antagonists were optimized for potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells. Compounds that met acceptable ADME criteria, selectivity, human plasma protein binding, potency shift in the presence of α-glycoprotein were evaluated in rat and dog pharmacokinetics.

Determination of hydrogen peroxide concentration using a handheld Raman spectrometer: Detection of an explosives precursor.

It has been shown that a handheld Raman spectrometer can be used to determine hydrogen peroxide concentration in aqueous solutions in seconds. To allow quantitative analysis, the aqueous peroxide samples were mixed 50/50 (v/v) with a 4mol/dm(3) sodium perchlorate solution which acted as the internal standard. Standard calibration using relative peak heights of the strongest perchlorate (932cm(-1)) and peroxide bands (876cm(-1)) gave an average error of 1.

Design and synthesis of pyridin-2-yloxymethylpiperidin-1-ylbutyl amide CCR5 antagonists that are potent inhibitors of M-tropic (R5) HIV-1 replication.

A novel series of CCR5 antagonists were identified based on the redesign of Schering C. An SAR was established based on inhibition of CCR5 (RANTES) binding and these compounds exhibited potent inhibition of R5 HIV-1 replication in peripheral blood mononuclear cells.

Metal compounds for the treatment of parasitic diseases.

The cysteine proteases of the trypanosomatid parasitic protozoa have been validated as targets for chemotherapy of Chagas' disease and leishmaniasis. Metal complexes of gold, platinum, iridium, palladium, rhodium and osmium have been reported to have activity against a variety of trypanosomatids, but the molecular target of these compounds has not been defined. The activity of gold(III) and palladium(II) cyclometallated complexes, and oxorhenium(V) complexes against mammalian and parasitic cysteine proteases was investigated.

Mammalian cell-seeded hydrogel microarrays printed via dip-pin technology.

Although significant advances have been made in the development of DNA and protein microarrays, less effort has been put toward developing mammalian cell microarrays. Such cellular microarrays may be useful in examining the effects of biological or chemical agents on cells, particularly in drug development and toxicological applications. Here, mammalian cell-seeded hydrogel microarrays were created using two different commercial microarrayers, with four different pin types.

Rhenium inhibitors of cathepsin B (ReO(SYS)X (where Y = S, py; X = Cl, Br, SPhOMe-p)): Synthesis and mechanism of inhibition.

The synthesis of four new oxorhenium(V) complexes containing the "3 + 1" mixed-ligand donor set, ReO(SYS)X (where Y = S, py; X = Cl, Br), is described. All of the complexes tested exhibited selectivity for cathepsin B over K. Most notably, compound 6, ReO(SSS-2,2')Br (IC50(cathepsin B) = 1.

Mekong River fish conservation zones in southern Laos: assessing effectiveness using local ecological knowledge.

Small-scale fisheries are important in Laos, where rural people heavily depend upon Mekong River and tributary fish stocks for their livelihoods. Increasing pressures from human exploitation and habitat disturbance, however, have raised serious concerns about the potential depletion of various species. This has led to the establishment of large numbers of Fish Conservation Zones (FCZs) or "no-take" fish sanctuaries in southern Laos based on a "community-based fisheries co-management" framework.

An open-label trial of stavudine, lamivudine and efavirenz in the treatment of HIV-positive, treatment-naive patients, and implications for clinical practice.

A phase II, open-label study of stavudine, lamivudine and efavirenz resulted in significant reductions in plasma HIV-1 RNA over a 24 week period in human immunodeficiency virus (HIV)-infected individuals. The trial currently has 68 patients, and this presentation covers data on the first 42 patients enrolled for 24 weeks. The mean plasma HIV-1 RNA on entry was 75858 HIV RNA copies/ml, and the mean CD4 count was 380 cells/mm3.

Biodiversity conservation and resource tenure regimes: a case study from northeast Cambodia.

The management of tropical protected areas is a contentious issue in resource management and often leads to an unproductive polarization of viewpoints supporting either "protectionist" or "sustainable development" paradigms. This paper argues for a context-driven approach whereby effective management requires inputs from both paradigms in different situations. A key element of context is understanding long-practiced resource tenures and their ability to meet future conservation and livelihood goals.