Gaining insights from Candida biofilm heterogeneity: one size does not fit all

Despite their clinical significance and substantial human health burden, fungal infections remain relatively under-appreciated. The widespread overuse of antibiotics and the increasing requirement for indwelling medical devices provides an opportunistic potential for the overgrowth and colonization of pathogenic Candida species on both biological and inert substrates. Indeed, it is now widely recognized that biofilms are a highly important part of their virulence repertoire. Candida albicans is regarded as the primary fungal biofilm forming species, yet there is also increasing interest and growing body of evidence for non-Candida albicans species (NCAS) biofilms, and interkingdom biofilm interactions. C. albicans biofilms are heterogeneous structures by definition, existing as three-dimensional populations of yeast, pseudo-hyphae, and hyphae, embedded within a self-produced extracellular matrix. Classical molecular approaches, driven by extensive studies of laboratory strains and mutants, have enhanced our knowledge and understanding of how these complex communities develop, thrive, and cause host-mediated damage. Yet our clinical observations tell a different story, with differential patient responses potentially due to inherent biological heterogeneity from specific clinical isolates associated with their infections. This review explores some of the recent advances made in an attempt to explore the importance of working with clinical isolates, and what this has taught us

Trends in BMI of Indonesian adults between 1993 and 2014: a longitudinal population-based study

Abstract Objective: To examine the trajectories of BMI in Indonesian adults from 1993 to 2014, investigating different patterns by sex and birth cohort. Design: Longitudinal study: secondary data analysis of the Indonesian Family Life Survey, a large-scale population-based longitudinal study, had their height and weight measured up to five times throughout the 21-year study period (1993–2014). The change in BMI across time was estimated using group-based trajectory models, then differences by sex and birth cohort were investigated using random effect (mixed) models. Setting: Thirteen out of twenty-seven provinces in Indonesia. Participants: Indonesian adults aged 19 years and older (n 42 537) were included in the analysis. Results: Mean BMI in adults increased between 1993 (21·4 kg/m2) and 2014 (23·5 kg/m2). The group-based trajectory model found three distinct groups with mean BMI increasing more rapidly in the most recent time periods. The first group (56·7 % of participants) had a mean BMI entirely within the normal weight range; the second group (34·7 %) started in the normal weight category and were obese, on average by the end of the study period; and the third group (8·6 %) were always in the obese category, on average. The shape of these three trajectories differed by gender (P < 0·001) and birth cohort (P < 0·001). Conclusions: The mean BMI among Indonesian adults has increased between 1993 and 2014, driven by those in the most recent birth cohorts. Our findings support the urgent need for targeted overweight and obesity prevention and intervention programmes in Indonesia

Social identity and acceptability of wild pig (Sus scrofa) control actions: A case study of Texas hunters

Wild pigs (Sus scrofa) pose significant challenges to wildlife managers. This research explored Texas hunters’ acceptability of wild pig control actions, and whether acceptability varied according to hunters’ affiliation with four different categories of natural resource organizations as an indicator of social identity. Results of a survey (n = 37,317) revealed that most hunters were accepting of all control actions except toxicants and non-lethal deterrents. Mean acceptability scores for each action differed significantly across the four affiliation categories, but effect sizes were minimal. Hunters affiliated with agricultural organizations were the most accepting of control actions, while hunters with no organizational affiliations were least accepting. Findings suggested that while the type of organization with which a hunter affiliates provides some basis for predicting acceptability of control actions, the association is likely not significant enough to warrant differentiating wild pig outreach messaging on the basis of affiliation

Measuring children\u27s sodium and potassium intakes in NZ: a pilot study

Low sodium and high potassium intakes in childhood protect against rises in blood pressure (BP) and risk of cardiovascular disease (CVD) later in life. Our aim was to pilot methods for collection of 24-h urine samples (gold standard) and diet recalls to assess sodium and potassium intakes and their food sources in 30 children aged 8⁻11 years at one New Zealand primary school. A diverse sample (n = 27) was recruited over a two-week period. All children provided a urine sample (71% complete) and interviewer-assisted 24-h diet recall (Intake24 software). Median (range) sodium intake was 2191 (1087 to 4786) mg/day (salt equivalent 5.5 g), potassium intake was 1776 (800⁻2981) mg/day, BP was 105 (84⁻129)/62 (53⁻89) mmHg, and sodium to potassium molar ratio was 2.0 (1.1⁻4.8). Frequent use of discretionary salt was uncommon. Major food sources of sodium were bread, pies and pastries, and bread and pasta-based dishes, and potassium were sauces and condiments, dairy products, and non-alcoholic beverages. Most participants provided adequate data and enjoyed taking part. A larger survey is warranted to confirm findings and inform a potential intervention(s). Small improvements to study procedures and resources should improve completeness of urine samples and quality of 24-h diet recall data

The Emission Line Properties of Gravitationally-lensed 1.5 < z < 5 Galaxies

We present and analyse near-infrared spectroscopy for a sample of 28 gravitationally- lensed star-forming galaxies in the redshift range 1.5 < z < 5, observed mostly with the Keck II telescope. With typical magnifications of ~1.5-4 magnitudes, our survey provides a valuable census of star formation rates, gas-phase metallicities and dynamical masses for a representative sample of low luminosity galaxies seen at a formative period in cosmic history. We find less evolution in the mass-metallicity relation compared to earlier work that focused on more luminous systems with z - 2-3, especially in the low mass (- 10^9 Msol) where our sample is - 0.25 dex more metal-rich. We interpret this offset as a result of the lower star formation rates (typically a factor of -10 lower) for a given stellar mass in our sub-luminous systems. Taking this effect into account, we conclude our objects are consistent with a fundamental metallicity relation recently proposed from unlensed observations.Comment: 22 pages, 12 figures, MNRAS, version including proof correction

Ecological correlates of risk and incidence of West Nile virus in the United States

West Nile virus, which was recently introduced to North America, is a mosquito-borne pathogen that infects a wide range of vertebrate hosts, including humans. Several species of birds appear to be the primary reservoir hosts, whereas other bird species, as well as other vertebrate species, can be infected but are less competent reservoirs. One hypothesis regarding the transmission dynamics of West Nile virus suggests that high bird diversity reduces West Nile virus transmission because mosquito blood-meals are distributed across a wide range of bird species, many of which have low reservoir competence. One mechanism by which this hypothesis can operate is that high-diversity bird communities might have lower community-competence, defined as the sum of the product of each species’ abundance and its reservoir competence index value. Additional hypotheses posit that West Nile virus transmission will be reduced when either: (1) abundance of mosquito vectors is low; or (2) human population density is low. We assessed these hypotheses at two spatial scales: a regional scale near Saint Louis, MO, and a national scale (continental USA). We found that prevalence of West Nile virus infection in mosquito vectors and in humans increased with decreasing bird diversity and with increasing reservoir competence of the bird community. Our results suggest that conservation of avian diversity might help ameliorate the current West Nile virus epidemic in the USA

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0–49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed myelination and, less frequently, thalamic signal intensity changes evolving over time. Typical muscle biopsy features included fibre size variability, central/internal nuclei, abnormal glycogen storage, presence of autophagic vacuoles and secondary mitochondrial abnormalities. Nerve biopsy performed in one case revealed subtotal absence of myelinated axons. Post-mortem examinations in three patients confirmed neurodevelopmental and neurodegenerative features and multisystem involvement. Finally, downregulation of epg5 (CG14299) in Drosophila resulted in autophagic abnormalities and progressive neurodegeneration. We conclude that EPG5-related Vici syndrome defines a novel group of neurodevelopmental disorders that should be considered in patients with suggestive features in whom mitochondrial, glycogen, or lysosomal storage disorders have been excluded. Neurological progression over time indicates an intriguing link between neurodevelopment and neurodegeneration, also supported by neurodegenerative features in epg5-deficient Drosophila, and recent implication of other autophagy regulators in late-onset neurodegenerative disease

Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol

Abstract Background The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. Methods Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. Discussion SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. Trial registration NCT03331991 . Registered on November 6, 2017.https://deepblue.lib.umich.edu/bitstream/2027.42/146186/1/12879_2018_Article_3444.pd

Sodium and health : old myths and a controversy based on denial

Purpose of Review: The scientific consensus on which global health organizations base public health policies is that high sodium intake increases blood pressure (BP) in a linear fashion contributing to cardiovascular disease (CVD). A moderate reduction in sodium intake to 2000 mg per day helps ensure that BP remains at a healthy level to reduce the burden of CVD. Recent Findings: Yet, since as long ago as 1988, and more recently in eight articles published in the European Heart Journal in 2020 and 2021, some researchers have propagated a myth that reducing sodium does not consistently reduce CVD but rather that lower sodium might increase the risk of CVD. These claims are not well-founded and support some food and beverage industry’s vested interests in the use of excessive amounts of salt to preserve food, enhance taste, and increase thirst. Nevertheless, some researchers, often with funding from the food industry, continue to publish such claims without addressing the numerous objections. This article analyzes the eight articles as a case study, summarizes misleading claims, their objections, and it offers possible reasons for such claims. Summary: Our study calls upon journal editors to ensure that unfounded claims about sodium intake be rigorously challenged by independent reviewers before publication; to avoid editorial writers who have been co-authors with the subject paper’s authors; to require statements of conflict of interest; and to ensure that their pages are used only by those who seek to advance knowledge by engaging in the scientific method and its collegial pursuit. The public interest in the prevention and treatment of disease requires no less