The role of trabeculectomy in enhancing glaucoma patient's quality of life.

Purpose: Is to control intraocular pressure (IOP) (up to 21 mmHg), to decrease medical treatment after trabeculectomy and to slow down or stop progression and deterioration in visual fields in glaucoma patients.

Methods: A retrospective study. The charts of all trabeculectomies done in the Department of Ophthalmology at the Skåne University Hospital, Sweden during 2010 were retrospectively evaluated.

Probing the Interaction of Aspergillomarasmine A with Metallo-β-lactamases NDM-1, VIM-2, and IMP-7.

Metallo-β-lactamases (MBLs) are a growing threat to the continued efficacy of β-lactam antibiotics. Recently, aspergillomarasmine A (AMA) was identified as an MBL inhibitor, but the mode of inhibition was not fully characterized. Equilibrium dialysis and metal analysis studies revealed that 2 equiv of AMA effectively removes 1 equiv of Zn(II) from MBLs NDM-1, VIM-2, and IMP-7 when the MBL is at micromolar concentrations.

Scaling up quality improvement intervention for perinatal care in Nepal (NePeriQIP); study protocol of a cluster randomised trial.

Introduction: Nepal Perinatal Quality Improvement Project (NePeriQIP) intends to scale up a quality improvement (QI) intervention for perinatal care according to WHO/National guidelines in hospitals of Nepal using the existing health system structures. The intervention builds on previous research on the implementation of Helping Babies Breathe-quality improvement cycle in a tertiary healthcare setting in Nepal. The objective of this study is to evaluate the effect of this scaled-up intervention on perinatal health outcomes.

Clonal Heterogeneity Influences the Fate of New Adaptive Mutations.

The joint contribution of pre-existing and de novo genetic variation to clonal adaptation is poorly understood but essential to designing successful antimicrobial or cancer therapies. To address this, we evolve genetically diverse populations of budding yeast, S. cerevisiae, consisting of diploid cells with unique haplotype combinations.

Evaluation of intraoperative analgesia provided by incisional lidocaine and bupivacaine in cats undergoing ovariohysterectomy.

Objectives The objective of this study was to assess the intraoperative analgesic effect of preoperative infiltration of the incision site with lidocaine or a mixture of lidocaine with bupivacaine in cats undergoing ovariohysterectomy (OHE). Methods This was a prospective, randomised clinical study. Healthy female intact cats (n = 75) undergoing OHE under medetomidine-ketamine-buprenorphine anaesthesia were assigned randomly into three treatment groups (n = 25 per group) to receive one of two local anaesthesia protocols or placebo preoperatively in the midline incision: lidocaine 1.

Clinical Variants of New Delhi Metallo-β-Lactamase Are Evolving To Overcome Zinc Scarcity.

Use and misuse of antibiotics have driven the evolution of serine β-lactamases to better recognize new generations of β-lactam drugs, but the selective pressures driving evolution of metallo-β-lactamases are less clear. Here, we present evidence that New Delhi metallo-β-lactamase (NDM) is evolving to overcome the selective pressure of zinc(II) scarcity. Studies of NDM-1, NDM-4 (M154L), and NDM-12 (M154L, G222D) demonstrate that the point mutant M154L, contained in 50% of clinical NDM variants, selectively enhances resistance to the penam ampicillin at low zinc(II) concentrations relevant to infection sites.

A Neolithic expansion, but strong genetic structure, in the independent history of New Guinea.

New Guinea shows human occupation since ~50 thousand years ago (ka), independent adoption of plant cultivation ~10 ka, and great cultural and linguistic diversity today. We performed genome-wide single-nucleotide polymorphism genotyping on 381 individuals from 85 language groups in Papua New Guinea and find a sharp divide originating 10 to 20 ka between lowland and highland groups and a lack of non-New Guinean admixture in the latter. All highlanders share ancestry within the last 10 thousand years, with major population growth in the same period, suggesting population structure was reshaped following the Neolithic lifestyle transition.

Body Mass Index Development and Asthma Throughout Childhood.

Several studies have found an association between overweight and asthma, yet the temporal relationship between their onsets remains unclear. We investigated the development of body mass index (BMI) from birth to adolescence among 2,818 children with and without asthma from a Swedish birth cohort study, the BAMSE (a Swedish acronym for "children, allergy, milieu, Stockholm, epidemiology") Project, during 1994-2013. Measured weight and height were available at 13 time points throughout childhood.

Dipicolinic Acid Derivatives as Inhibitors of New Delhi Metallo-β-lactamase-1.

The efficacy of β-lactam antibiotics is threatened by the emergence and global spread of metallo-β-lactamase (MBL) mediated resistance, specifically New Delhi metallo-β-lactamase-1 (NDM-1). By utilization of fragment-based drug discovery (FBDD), a new class of inhibitors for NDM-1 and two related β-lactamases, IMP-1 and VIM-2, was identified. On the basis of 2,6-dipicolinic acid (DPA), several libraries were synthesized for structure-activity relationship (SAR) analysis.

Sustainability of knowledge implementation in a low- and middle- income context: Experiences from a facilitation project in Vietnam targeting maternal and neonatal health.

Background: In a previous trial in Vietnam, a facilitation strategy to secure evidence-based practice in primary care resulted in reduced neonatal mortality over a period of three years. While little is known as to what ensures sustainability in the implementation of community-based strategies, the aim of this study was to investigate factors promoting or hindering implementation, and sustainability of knowledge implementation strategies, by means of the former Neonatal Knowledge Into Practice (NeoKIP) trial.

Methods: In 2014 we targeted all levels in the Vietnamese healthcare system: six individual interviews with representatives at national, provincial and district levels, and six focus group discussions with representatives at the commune level.

Perceived impact of stroke six years after onset, and changes in impact between one and six years.

Objective: To examine the perceived impact of stroke between 1 and 6 years after stroke using the Stroke Impact Scale 3.0 (SIS).

Design: A prospective longitudinal study.

Nitrogen effects on the pelagic food web are modified by dissolved organic carbon.

Global environmental change has altered the nitrogen (N) cycle and enhanced terrestrial dissolved organic carbon (DOC) loadings to northern boreal lakes. However, it is still unclear how enhanced N availability affects pelagic food web efficiency (FWE) and crustacean zooplankton growth in N limited boreal lakes. Here, we performed in situ mesocosm experiments in six unproductive boreal Swedish lakes, paired across a DOC gradient, with one lake in each pair fertilized with N (2011: reference year; 2012, 2013: impact years).

Genetic and epigenetic regulation of YKL-40 in childhood.

Background: Circulating levels of the chitinase-like protein YKL-40 are influenced by genetic variation in its encoding gene (chitinase 3-like 1 [CHI3L1]) and are increased in patients with several diseases, including asthma. Epigenetic regulation of circulating YKL-40 early in life is unknown.

Objective: We sought to determine (1) whether methylation levels at CHI3L1 CpG sites mediate the association of CHI3L1 single nucleotide polymorphisms (SNPs) with YKL-40 levels in the blood and (2) whether these biomarkers (CHI3L1 SNPs, methylation profiles, and YKL-40 levels) are associated with asthma in early childhood.

Experiences of Daily Life Among Adolescents With Asthma - A Struggle With Ambivalence.

Objective: There is limited knowledge about how adolescents with asthma view their disease in daily life and how these views impact on management. The aim of this study was to describe experiences of daily life, with particular focus on thoughts, feelings and management of adolescents with asthma.

Methods: In this qualitative study, data were obtained from 10 interviews with adolescents (aged 16-18 years) with asthma recruited from the Swedish population-based prospective birth cohort, BAMSE.

Differential requirement of SUFU in tissue development discovered in a hypomorphic mouse model.

Suppressor of Fused (SUFU) is an essential negative regulator of the Hedgehog (HH) pathway and involved in GLI transcription factor regulation. Due to early embryonic lethality of Sufu mice, investigations of SUFU's role later in development are limited to conditional, tissue-specific knockout models. In this study we developed a mouse model (Sufu) with hypomorphic features where embryos were viable up to E18.

A population-based study of self-reported skin exposures and symptoms in relation to contact allergy in adolescents.

Background: Knowledge about the relations between skin exposures, skin symptoms and contact allergy in adolescents is limited.

Objectives: To explore self-reported skin exposures and skin symptoms in girls and boys, and to assess the associations between exposures, symptoms and contact allergy at age 16 years.

Participants And Methods: In all, 3115 adolescents from the population-based BAMSE birth cohort answered a questionnaire at age 16 concerning various skin exposures and related skin symptoms.

Discovery of 1-Hydroxypyridine-2(1H)-thione-6-carboxylic Acid as a First-in-Class Low-Cytotoxic Nanomolar Metallo β-Lactamase Inhibitor.

VIM-2 is one of the most common carbapenem-hydrolyzing metallo β-lactamases (MBL) found in many drug-resistant Gram-negative bacterial strains. Currently, there is a lack of effective lead compounds with optimal therapeutic potential within our drug development pipeline. Here we report the discovery of 1-hydroxypyridine-2(1H)-thione-6-carboxylic acid (3) as a first-in-class metallo β-lactamase inhibitor (MBLi) with a potent inhibition K of 13 nm against VIM-2 that corresponds to a remarkable 0.

IgE sensitization in relation to preschool eczema and filaggrin mutation.

Background: Eczema (atopic dermatitis) is associated with an increased risk of having IgE antibodies. IgE sensitization can occur through an impaired skin barrier. Filaggrin gene (FLG) mutation is associated with eczema and possibly also with IgE sensitization.

Y-chromosomal sequences of diverse Indian populations and the ancestry of the Andamanese.

We present 42 new Y-chromosomal sequences from diverse Indian tribal and non-tribal populations, including the Jarawa and Onge from the Andaman Islands, which are analysed within a calibrated Y-chromosomal phylogeny incorporating South Asian (in total 305 individuals) and worldwide (in total 1286 individuals) data from the 1000 Genomes Project. In contrast to the more ancient ancestry in the South than in the North that has been claimed, we detected very similar coalescence times within Northern and Southern non-tribal Indian populations. A closest neighbour analysis in the phylogeny showed that Indian populations have an affinity towards Southern European populations and that the time of divergence from these populations substantially predated the Indo-European migration into India, probably reflecting ancient shared ancestry rather than the Indo-European migration, which had little effect on Indian male lineages.

Contrasting evolutionary genome dynamics between domesticated and wild yeasts.

Structural rearrangements have long been recognized as an important source of genetic variation, with implications in phenotypic diversity and disease, yet their detailed evolutionary dynamics remain elusive. Here we use long-read sequencing to generate end-to-end genome assemblies for 12 strains representing major subpopulations of the partially domesticated yeast Saccharomyces cerevisiae and its wild relative Saccharomyces paradoxus. These population-level high-quality genomes with comprehensive annotation enable precise definition of chromosomal boundaries between cores and subtelomeres and a high-resolution view of evolutionary genome dynamics.

Trends in paediatric asthma hospitalisations - differences between neighbouring countries.

Paediatric asthma hospitalisation trends in Finland and Sweden over the past 10 years are unclear. We investigated the incidence of paediatric asthma hospitalisations in both countries from 2005 to 2014, using Finland's National Hospital Discharge Register and Sweden's National Patient Register which cover all hospitalisations in the respective countries. During the study period, the incidence of paediatric asthma hospitalisations decreased by 51% in Finland, but remained stable in Sweden.

Sensitization trajectories in childhood revealed by using a cluster analysis.

Background: Assessment of sensitization at a single time point during childhood provides limited clinical information. We hypothesized that sensitization develops as specific patterns with respect to age at debut, development over time, and involved allergens and that such patterns might be more biologically and clinically relevant.

Objective: We sought to explore latent patterns of sensitization during the first 6 years of life and investigate whether such patterns associate with the development of asthma, rhinitis, and eczema.

Phthalates, non-phthalate plasticizers and bisphenols in Swedish preschool dust in relation to children's exposure.

Children are exposed to a wide range of chemicals in their everyday environments, including the preschool. In this study, we evaluated the levels of phthalates, non-phthalate plasticizers and bisphenols in dust from 100 Swedish preschools and identified important exposure factors in the indoor environment. In addition, children's total exposure to these chemicals was determined by urine analysis to investigate their relation with dust exposure, and to explore the time trends by comparing with children who provided urine fifteen years earlier.