Sclerocornea in a patient with van den Ende-Gupta syndrome homozygous for a SCARF2 microdeletion.

Van den Ende-Gupta Syndrome (VDEGS) is an autosomal recessive disorder characterized by blepharophimosis, distinctive nose, hypoplastic maxilla, and skeletal abnormalities. Using homozygosity mapping in four VDEGS patients from three consanguineous families, Anastacio et al. [Anastacio et al.

Distribution and dissemination of the Val1016Ile and Phe1534Cys Kdr mutations in Aedes aegypti Brazilian natural populations.

Background: The chemical control of the mosquito Aedes aegypti, the major vector of dengue, is being seriously threatened due to the development of pyrethroid resistance. Substitutions in the 1016 and 1534 sites of the voltage gated sodium channel (AaNaV), commonly known as kdr mutations, confer the mosquito with knockdown resistance. Our aim was to evaluate the allelic composition of natural populations of Brazilian Ae.

Improving the modeling of disease data from the government surveillance system: a case study on malaria in the Brazilian Amazon.

The study of the effect of large-scale drivers (e.g., climate) of human diseases typically relies on aggregate disease data collected by the government surveillance network.

Dissolved hydrogen and nitrogen fixation in the oligotrophic North Pacific Subtropical Gyre.

The production of hydrogen (H2) is an inherent component of biological dinitrogen (N2) fixation, and there have been several studies quantifying H2 production relative to N2 fixation in cultures of diazotrophs. However, conducting the relevant measurements for a field population is more complex as shown by this study of N2 fixation, H2 consumption and dissolved H2 concentrations in the oligotrophic North Pacific Ocean. Measurements of H2 oxidation revealed microbial consumption of H2 was equivalent to 1-7% of ethylene produced during the acetylene reduction assay and 11-63% of (15)N2 assimilation on a molar scale.

Rotavirus epidemiology before and after vaccine introduction.

Objectives: To evaluate the prevalence and circulation of rotavirus genotypes before and after the introduction of oral vaccine against human rotavirus, and to check for a possible change in the age of occurence of the infection by RV-A.

Methods: This was a cross-sectional study conducted between 2002-2011, in the city of Juiz de Fora, state of Minas Gerais, Brazil. A total of 1,144 diarrheal stool specimens were obtained from nonhospitalized children aged between 0 and 5 years, and analyzed by polyacrylamide gel electrophoresis and reverse-transcription polymerase chain reaction for genotype characterization.

Total synthesis of (+)-trienomycins A and F via C-C bond-forming hydrogenation and transfer hydrogenation.

The triene-containing C17-benzene ansamycins trienomycins A and F were prepared in 16 steps (longest linear sequence, LLS) and 28 total steps. The C11-C13 stereotriad was generated via enantioselective Ru-catalyzed alcohol CH syn crotylation followed by chelation-controlled carbonyl dienylation. Enantioselective Rh-catalyzed acetylene-aldehyde reductive coupling mediated by gaseous H2 was used to form a diene that ultimately was subjected to diene-diene ring closing metathesis to form the macrocycle.

Mitigation of cardiovascular toxicity in a series of CSF-1R inhibitors, and the identification of AZD7507.

The potent and selective 3-amido-4-anilinoquinoline CSF-1R inhibitor AZ683 suffered from cardiovascular liabilities, which were linked to the off-target activities of the compound and ion channel activity in particular. Less basic and less lipophilic examples from both the quinoline and cinnoline series demonstrated cleaner secondary pharmacology profiles. Cinnoline 31 retained the required potency and oral PK profile, and was progressed through the safety screening cascade to be nominated into development as AZD7507.

Epidemiology of injuries in the elite level female high school lacrosse player.

Female lacrosse has grown 219% in the last decade. This descriptive study explored the epidemiology of elite female high school lacrosse injuries and compared them with those in the collegiate player. Five hundred surveys were completed at tournaments in the northeast United States.

Abundance of water bodies is critical to guide mosquito larval control interventions and predict risk of mosquito-borne diseases.

Characterization of mosquito breeding habitats is often accomplished with the goal of guiding larval control interventions as well as the goal of identifying areas with higher disease risk. This characterization often relies on statistical measures of association (e.g.

Corneal cross linking and infectious keratitis: a systematic review with a meta-analysis of reported cases.

Background: Collagen cross linking (CXL) of the cornea has been developed recently as a new treatment for multidrug-resistant infectious keratitis. The aim of this study is to summarize the previously published data and evaluate the effectiveness of this treatment.

Results: The search identified 12 articles.

Multiple variants aggregate in the neuregulin signaling pathway in a subset of schizophrenia patients.

Despite the strongly held view that schizophrenia (SZ) shows substantial genetic heterogeneity, pathway heterogeneity, as seen in cancer where different pathways are affected in similar tumors, has not been explored. We explore this possibility in a case-only study of the neuregulin signaling pathway (NSP), which has been prominently implicated in SZ and for which there is detailed knowledge on the ligand- and receptor-processing steps through β- and γ-secretase cleavage. We hypothesize that more than one damaging variants in the NSP genes might be necessary to cause disease, leading to an apparent clustering of such variants in only the few patients with affected NSP.

Assessing the effects of Aedes aegypti kdr mutations on pyrethroid resistance and its fitness cost.

Pyrethroids are the most used insecticide class worldwide. They target the voltage gated sodium channel (NaV), inducing the knockdown effect. In Aedes aegypti, the main dengue vector, the AaNaV substitutions Val1016Ile and Phe1534Cys are the most important knockdown resistance (kdr) mutations.

Effect of triflumuron, a chitin synthesis inhibitor, on Aedes aegypti, Aedes albopictus and Culex quinquefasciatus under laboratory conditions.

Background: Resistance to traditional insecticides represents a threat to the control of disease vectors. The insect growth regulators (IGR) are a potential alternative to control mosquitoes, including resistant populations. The chitin synthesis inhibitors (CSI) are IGRs, which interfere with the insect molting process and represent one major class of compounds against Aedes aegypti populations resistant to the larvicide organophosphate temephos.

Conservation efforts may increase malaria burden in the Brazilian Amazon.

Background: Large-scale forest conservation projects are underway in the Brazilian Amazon but little is known regarding their public health impact. Current literature emphasizes how land clearing increases malaria incidence, leading to the conclusion that forest conservation decreases malaria burden. Yet, there is also evidence that proximity to forest fringes increases malaria incidence, which implies the opposite relationship between forest conservation and malaria.

PhenoDB: a new web-based tool for the collection, storage, and analysis of phenotypic features.

To interpret whole exome/genome sequence data for clinical and research purposes, comprehensive phenotypic information, knowledge of pedigree structure, and results of previous clinical testing are essential. With these requirements in mind and to meet the needs of the Centers for Mendelian Genomics project, we have developed PhenoDB (http://phenodb.net), a secure, Web-based portal for entry, storage, and analysis of phenotypic and other clinical information.

Inactivation of the microRNA-183/96/182 cluster results in syndromic retinal degeneration.

The microRNA-183/96/182 cluster is highly expressed in the retina and other sensory organs. To uncover its in vivo functions in the retina, we generated a knockout mouse model, designated "miR-183C(GT/GT)," using a gene-trap embryonic stem cell clone. We provide evidence that inactivation of the cluster results in early-onset and progressive synaptic defects of the photoreceptors, leading to abnormalities of scotopic and photopic electroretinograms with decreased b-wave amplitude as the primary defect and progressive retinal degeneration.

Implementing genomic medicine in the clinic: the future is here.

Although the potential for genomics to contribute to clinical care has long been anticipated, the pace of defining the risks and benefits of incorporating genomic findings into medical practice has been relatively slow. Several institutions have recently begun genomic medicine programs, encountering many of the same obstacles and developing the same solutions, often independently. Recognizing that successful early experiences can inform subsequent efforts, the National Human Genome Research Institute brought together a number of these groups to describe their ongoing projects and challenges, identify common infrastructure and research needs, and outline an implementation framework for investigating and introducing similar programs elsewhere.

Psychotropic medications and falls in nursing homes: a cross-sectional study.

Background: Psychotropic medications are very frequently used in nursing homes and have been associated with falls. Little is known on the potential differences between types and subtypes of these medications, and also regarding different prescription patterns.

Methods: Data from 4502 residents living in 41 nursing homes belonging to a Spanish private chain were collected during a study period of 1 month and analyzed.

Percutaneous ultrasound-guided laser ablation is effective for treating selected nodal metastases in papillary thyroid cancer.

Context: Mini-invasive procedures may be useful for control of local neck nodal metastases of papillary thyroid cancer (PTC) in high-risk patients.

Objective: Our objective was to assess the effectiveness and safety of ultrasound (US)-guided laser ablation (LA) for nonsurgical treatment of small-size neck metastases of PTC.

Design And Setting: We conducted a pilot study on a surgically controlled metastasis, followed by a prospective trial with a 12-month follow-up.

Fitness evaluation of two Brazilian Aedes aegypti field populations with distinct levels of resistance to the organophosphate temephos.

In Brazil, decades of dengue vector control using organophosphates and pyrethroids have led to dissemination of resistance. Although these insecticides have been employed for decades against Aedes aegypti in the country, knowledge of the impact of temephos resistance on vector viability is limited. We evaluated several fitness parameters in two Brazilian Ae.

Why do we need alternative tools to control mosquito-borne diseases in Latin America?

In this opinion paper, we discuss the potential and challenges of using the symbiont Wolbachia to block mosquito transmitted diseases such as dengue, malaria and chikungunya in Latin America.

The classification of esterases: an important gene family involved in insecticide resistance--a review.

The use of chemical insecticides continues to play a major role in the control of disease vector populations, which is leading to the global dissemination of insecticide resistance. A greater capacity to detoxify insecticides, due to an increase in the expression or activity of three major enzyme families, also known as metabolic resistance, is one major resistance mechanisms. The esterase family of enzymes hydrolyse ester bonds, which are present in a wide range of insecticides; therefore, these enzymes may be involved in resistance to the main chemicals employed in control programs.