Metabolic and immunological responses of Drosophila melanogaster to dietary restriction and bacterial infection differ substantially between genotypes in a population

To respond to changing environmental conditions, a population may either shift toward better-adapted genotypes or adapt on an individual level. The present work aimed to quantify the relevance of these two processes by comparing the responses of defined Drosophila melanogaster populations to different stressors. To do this, we infected two homogeneous populations (isofemale lines), which differ significantly in fitness, and a synthetic heterogeneous population with a specific pathogen and/or exposed them to food restriction. Pectobacterium carotovorum was used to infect Drosophila larvae either fed standard or protein-restricted diet. In particular, the two homogeneous groups, which diverged in their fitness, showed considerable differences in all parameters assessed (survivorship, protein and lipid contents, phenol-oxidase (PO) activity, and antibacterial rate). Under fully nutritious conditions, larvae of the homogeneous population with low fitness exhibited lower survivorship and protein levels, as well as higher PO activity and antibacterial rate compared with the fitter population. A protein-restricted diet and bacterial infection provoked a decrease in survivorship, and antibacterial rate in most populations. Bacterial infection elicited an opposite response in protein and lipid content in both isofemale lines tested. Interestingly, the heterogeneous population showed a complex response pattern. The response of the heterogeneous population followed the fit genotype in terms of survival and antibacterial activity but followed the unfit genotype in terms of PO activity. In conclusion, our results show that defined genotypes exhibit highly divergent responses to varying stressors that are difficult to predict. Furthermore, the responses of heterogeneous populations do not follow a fixed pattern showing a very high degree of plasticity and differences between different genotypes

Population pharmacokinetics of cefazolin in maternal and umbilical cord plasma, and simulated exposure in term neonates

Background:Intra-partum cefazolin is used to prevent group BStreptococcus(GBS) vertical transmission inmothers allergic to penicillin without a history of anaphylaxis.Objectives:To investigate the maternal cefazolin dose–exposure relationship and subsequent maternal andneonatal target attainment at delivery.Methods:Data were obtained from 24 healthy, GBS-colonized pregnant women (20–41 years), undergoing vagi-nal delivery (gestational age 37 weeks). During labour, all women received a 2 g cefazolin IV infusion. Eighthours later, eight women received another 1 g in the event of delayed (>8 h) delivery. Next to maternal plasmaconcentrations (up to 10 per dosing interval, until delivery), venous and arterial umbilical cord concentrationswere determined at delivery. Target attainment in maternal/neonatal plasma was set at 1 mg/L for 60% of thedosing interval (unbound cefazolin, worst-case clinical breakpoint). A population pharmacokinetic (popPK) modelwas built (NONMEM 7.4). ClinicalTrials.gov Identifier: NCT01295606.Results:At delivery, maternal blood and arterial umbilical cord unbound cefazolin concentrations were >1 mg/Lin 23/24 (95.8%) and 11/12 (91.7%), respectively. The popPK of cefazolin in pregnant women was described by atwo-compartment model with first-order elimination. Two additional compartments described the venous andarterial umbilical cord concentration data. Cefazolin target attainment was adequate in the studied cohort,where delivery occurred no later than 6.5 h after either the first or the second dose. PopPK simulations showedadequate maternal and umbilical cord exposure for 12 h following the first dose.Conclusions:PopPK simulations showed that standard pre-delivery maternal cefazolin dosing providedadequate target attainment up to the time of delivery

Epidemiology of Chlamydia trachomatis in the Middle East and north Africa: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: The epidemiology of Chlamydia trachomatis in the Middle East and north Africa is poorly understood. We aimed to provide a comprehensive epidemiological assessment of C trachomatis infection in the Middle East and north Africa. METHODS: We did a systematic review of C trachomatis infection as well as a meta-analysis and meta-regression of C trachomatis prevalence. We searched PubMed and Embase, as well as regional and national databases up to March 13, 2019, using broad search terms with no language or year restrictions. Any document or report including biological measures for C trachomatis prevalence or incidence was eligible for inclusion. We extracted all measures of current (genital or rectal), recent, and ever infection with C trachomatis. We estimated pooled average prevalence in different populations using random-effects meta-analysis. Factors associated with prevalence and sources of between-study heterogeneity were determined using meta-regression. FINDINGS: We identified a total of 1531 citations, of which 255 reports contributed to 552 C trachomatis prevalence measures from 20 countries. No incidence measures were identified. Pooled prevalence of current genital infection was 3·0% (95% CI 2·3-3·8) in general populations, 2·8% (1·0-5·2) in intermediate-risk populations, 13·2% (7·2-20·7) in female sex workers, 11·3% (9·0-13·7) in infertility clinic attendees, 12·4% (7·9-17·7) in women with miscarriage, 12·4% (9·4-15·7) in symptomatic women, and 17·4% (12·5-22·8) in symptomatic men. Pooled prevalence of current rectal infection was 7·7% (4·2-12·0) in men who have sex with men. Substantial between-study heterogeneity was found. Multivariable meta-regression explained 29·0% of variation. Population type was most strongly associated with prevalence. Additional associations were found with assay type, sample size, country, and sex, but not with sampling methodology or response rate (about 90% of studies used convenience sampling and >75% had unclear response rate). There was no evidence for temporal variation in prevalence between 1982 and 2018. INTERPRETATION: C trachomatis prevalence in the Middle East and north Africa is similar to other regions, but higher than expected given its sexually conservative norms. High prevalence in infertility clinic attendees and in women with miscarriage suggests a potential role for C trachomatis in poor reproductive health outcomes in this region. FUNDING: National Priorities Research Program from the Qatar National Research Fund (a member of Qatar Foundation)

Gender norms in music and dance : A qualitative study on preschool teachers' view on gender norms in preschool

Studiens syfte har varit att öka kunskapen om förskollärares olika synsätt på genus, i relation till barns estetiska uttrycksformer i dans och musik. Detta är en kvalitativ studie som genomfördes med hjälp av semistrukturerade intervjuer med sju förskollärare. Datainsamlingen skedde i flera kommuner i Sverige och därefter transkriberades och analyserades materialen gemensamt. Resultaten som framkom ur förskollärarintervjuerna tematiserades i fem teman/kategorier som är (1) Genus reproduceras i musik och dans, (2) Genusmedvetenheten kopplas till ålder, (3) Motsägelsefulla genusperspektiv förekommer- undermedvetna handlingar, (4) Förskollärarnas förhållningssätt har betydelse för genusarbetet -genusmedveten förskollärare deltar, bemöter och utmanar och (5) Hinder i genusarbetet inom musik och dans. Utifrån genussystemteorin har vi fokuserat på dikotomi och analyserat resultaten utifrån dikotomins synsätt om isärhållanden mellan kön.  Studien visar att förskollärare ser skillnader i hur pojkar och flickor deltar i musik och dans samt vilken musik och dans de dras till. Förskolläraren har en viktig roll i genusarbetet för att kunna motarbeta könsnormer. Resultatet visar även att förskollärare och tidigare forskning ser ett samband mellan barns dikotoma val och barnens ålder och att detta kan bero på att barns genusmedvetenhet ökar med åldern. Detta leder till slutsatsen att det råder medvetenhet kring uppdraget om en jämställd utbildning hos förskollärarna men att det fortfarande råder dikotomi mellan könen i dagens förskolor.

Microwaves for breast cancer treatments

Hyperthermia is potentially an effective method for the treatment of cancer, especially breast cancer tumors. One of the most attractive attributes of hyperthermia is the possibility of providing therapeutic benefit noninvasively, minimizing side effects. To be effective, a hyperthermia treatment must selectively heat the cancerous tissue, elevating the temperature in the tumor without exposing healthy tissue to excessive temperature elevations. In this paper, a suggested simple model of Annular Phased Array (APA) using eight half wavelength linear dipoles is presented. New software (COMSOL MULTIPHYSICS) is used to calculate the temperature distribution inside a model of a three layered breast (skin, breast tissue, and tumor). In addition, the effect of changing the amplitude and phases of the array elements on the temperature distributions and the conditions on the values of the phases are demonstrated in order to achieve the objective of hyperthermia for breast tumor treatment

Population pharmacokinetics of cefazolin in maternal and umbilical cord plasma, and simulated exposure in term neonates

Background: Intra-partum cefazolin is used to prevent group B Streptococcus (GBS) vertical transmission in mothers allergic to penicillin without a history of anaphylaxis. Objectives: To investigate the maternal cefazolin dose-exposure relationship and subsequent maternal and neonatal target attainment at delivery. Methods: Data were obtained from 24 healthy, GBS-colonized pregnant women (20-41 years), undergoing vaginal delivery (gestational age ≥37 weeks). During labour, all women received a 2 g cefazolin IV infusion. Eight hours later, eight women received another 1 g in the event of delayed (>8 h) delivery. Next to maternal plasma concentrations (up to 10 per dosing interval, until delivery), venous and arterial umbilical cord concentrations were determined at delivery. Target attainment in maternal/neonatal plasma was set at 1 mg/L for 60% of the dosing interval (unbound cefazolin, worst-case clinical breakpoint). A population pharmacokinetic (popPK) model was built (NONMEM 7.4). ClinicalTrials.gov Identifier: NCT01295606. Results: At delivery, maternal blood and arterial umbilical cord unbound cefazolin concentrations were >1 mg/L in 23/24 (95.8%) and 11/12 (91.7%), respectively. The popPK of cefazolin in pregnant women was described by a two-compartment model with first-order elimination. Two additional compartments described the venous and arterial umbilical cord concentration data. Cefazolin target attainment was adequate in the studied cohort, where delivery occurred no later than 6.5 h after either the first or the second dose. PopPK simulations showed adequate maternal and umbilical cord exposure for 12 h following the first dose. Conclusions: PopPK simulations showed that standard pre-delivery maternal cefazolin dosing provided adequate target attainment up to the time of delivery

Dosing of IV posaconazole to treat critically ill patients with invasive pulmonary aspergillosis:a population pharmacokinetics modelling and simulation study

Background: Posaconazole is used for the prophylaxis and treatment of invasive fungal infections in critically ill patients. Standard dosing was shown to result in adequate attainment of the prophylaxis C-min target (0.7 mg/L) but not of the treatment C-min target (1.0 mg/L). Objectives: To provide an optimized posaconazole dosing regimen for IV treatment of patients with invasive pulmonary aspergillosis in the ICU. Methods: A population pharmacokinetics (popPK) model was developed using data from the POSA-FLU PK substudy (NCT03378479). Monte Carlo simulations were performed to assess treatment C-min and AUC(0-24) PTA. PTA >= 90% was deemed clinically acceptable. PopPK modelling and simulation were performed using NONMEM 7.5. Results: Thirty-one patients with intensive PK sampling were included in the PK substudy, contributing 532 posaconazole plasma concentrations. The popPK of IV posaconazole was best described by a two-compartment model with linear elimination. Interindividual variability was estimated on clearance and volume of distribution in central and peripheral compartments. Posaconazole peripheral volume of distribution increased with bodyweight. An optimized loading regimen of 300 mg q12h and 300 mg q8h in the first two treatment days achieved acceptable PTA by Day 3 in patients <100 kg and >= 100 kg, respectively. A maintenance regimen of 400 mg q24h ensured >= 90% C-min PTA, whereas the standard 300 mg q24h was sufficient to achieve the AUC(0-24) target throughout 14 days, irrespective of bodyweight. Conclusions: We have defined a convenient, optimized IV posaconazole dosing regimen that was predicted to attain the treatment target in critically ill patients with invasive aspergillosis