Maternal Colonization Versus Nosocomial Transmission as the Source of Drug-Resistant Bloodstream Infection in an Indian Neonatal Intensive Care Unit: A Prospective Cohort Study.

BACKGROUND: Drug-resistant gram-negative (GN) pathogens are a common cause of neonatal sepsis in low- and middle-income countries. Identifying GN transmission patterns is vital to inform preventive efforts. METHODS: We conducted a prospective cohort study, 12 October 2018 to 31 October 2019 to describe the association of maternal and environmental GN colonization with bloodstream infection (BSI) among neonates admitted to a neonatal intensive care unit (NICU) in Western India. We assessed rectal and vaginal colonization in pregnant women presenting for delivery and colonization in neonates and the environment using culture-based methods. We also collected data on BSI for all NICU patients, including neonates born to unenrolled mothers. Organism identification, antibiotic susceptibility testing, and next-generation sequencing (NGS) were performed to compare BSI and related colonization isolates. RESULTS: Among 952 enrolled women who delivered, 257 neonates required NICU admission, and 24 (9.3%) developed BSI. Among mothers of neonates with GN BSI (n = 21), 10 (47.7%) had rectal, 5 (23.8%) had vaginal, and 10 (47.7%) had no colonization with resistant GN organisms. No maternal isolates matched the species and resistance pattern of associated neonatal BSI isolates. Thirty GN BSI were observed among neonates born to unenrolled mothers. Among 37 of 51 BSI with available NGS data, 21 (57%) showed a single nucleotide polymorphism distance of ≤5 to another BSI isolate. CONCLUSIONS: Prospective assessment of maternal GN colonization did not demonstrate linkage to neonatal BSI. Organism-relatedness among neonates with BSI suggests nosocomial spread, highlighting the importance of NICU infection prevention and control practices to reduce GN BSI.

Moderate prenatal alcohol exposure produces sex-specific social impairments and attenuates prelimbic excitability and amygdala-cortex modulation of adult social behaviour.

Lifelong social impairments are common in individuals with prenatal alcohol exposure (PAE), and preclinical studies have identified gestational day (G)12 as a vulnerable timepoint for producing social deficits following binge-level PAE. While moderate (m)PAE also produces social impairments, the long-term neuroadaptations underlying them are poorly understood. Activity of the projection from the basolateral amygdala to the prelimbic cortex (BLA â†’ PL) leads to social avoidance, and the PL is implicated in negative social behaviours, making each of these potential candidates for the neuroadaptations underlying mPAE-induced social impairments. To examine this, we first established that G12 mPAE produced sex-specific social impairments lasting into adulthood in Sprague-Dawley rats. We then chemogenetically inhibited the BLA â†’ PL using clozapine N-oxide (CNO) during adult social testing. This revealed that CNO reduced social investigation in control males but had no effect on mPAE males or females of either exposure, indicating that mPAE attenuated the role of this projection in regulating male social behaviour and highlighting one potential mechanism by which mPAE affects male social behaviour more severely. Using whole-cell electrophysiology, we also examined mPAE-induced changes to PL pyramidal cell physiology and determined that mPAE reduced cell excitability, likely due to increased suppression by inhibitory interneurons. Overall, this work identified two mPAE-induced neuroadaptations that last into adulthood and that may underlie the sex-specific vulnerability to mPAE-induced social impairments. Future research is necessary to expand upon how these circuits modulate both normal and pathological social behaviours and to identify sex-specific mechanisms, leading to differential vulnerability in males and females.

Short bouts of walking attenuates the response of IL-8 to prolonged sitting in healthy adults.

PURPOSE: Experimental studies have shown that prolonged sitting for 2-8 h can cause changes to vascular and metabolic markers; the response of pro-inflammatory cytokines is relatively unexplored. The purpose of this study is to determine the response of interleukin-8 (IL-8) to prolonged and interrupted sitting. METHODS: Healthy participants (n = 24, 21.1 years ± 2.2, 50% female) completed a prolonged sitting session (4 h) and an interrupted sitting session (4 h of sitting with 3 min of walking at 60%HRmax, every 30 min) in random order. Saliva and capillary plasma were collected at the beginning (T1) and at the end of each session (T2). RESULTS: Salivary concentrations of IL-8 increased during the prolonged (T1 median: 22.09 pg/mL, T2 median: 86.18 pg/mL; p = < 0.01, ES - 0.55) and interrupted (T1 median: 22.09 pg/mL, T2 median: 51.99 pg/mL; p = 0.021, ES - 0.34) sessions; however, the increase during interrupted sitting was lower (PS median: 134.4%, range: - 43.96 to 1115.69 and IS median: 50.8%, range: - 75.5 to 356.35; p = 0.011, ES - 0.53). In the sub-sample of males, salivary IL-8 did not increase in the interrupted session (T1 median: 22.09, range: 3.496-699.12, and T2 median: 24.96, range: 5.11-533.5, p = > 0.05, ES - 0.16). No significant findings were observed for IL-8 in the plasma. CONCLUSION: Prolonged sitting appears to increase concentrations of the pro-inflammatory cytokine IL-8 while interrupting this sitting with short bouts of walking blunts this response. Sex appears to moderate this relationship; however, there appears to be a large amount of individual variability.

Secretome-Mediated Interactions with Intestinal Epithelial Cells: A Role for Secretome Components from Lactobacillus rhamnosus R0011 in the Attenuation of Salmonella enterica Serovar Typhimurium Secretome and TNF-α-Induced Proinflammatory Responses.

Recent evidence suggests that lactic acid bacteria communicate with host cells via secretome components to influence immune responses but less is known about gut-pathogen secretomes, impact of lactic acid bacteria secretomes on host-pathogen interactions, and the mechanisms underlying these interactions. Genome-wide microarrays and cytokine profiling were used to interrogate the impact of the Lactobacillus rhamnosus R0011 secretome (LrS) on TNF-α and Salmonella enterica subsp. enterica serovar Typhimurium secretome (STS)-induced outcomes in human intestinal epithelial cells. The LrS attenuated both TNF-α- and STS-induced gene expression involved in NF-κB and MAPK activation, as well as expression of genes involved in other immune-related signaling pathways. Specifically, the LrS induced the expression of dual specificity phosphatase 1 (DUSP1), activating transcription factor 3 (ATF3), and tribbles pseudokinase 3 (TRIB3), negative regulators of innate immune signaling, in HT-29 intestinal epithelial cells challenged with TNF-α or STS. TNF-α- and STS-induced acetylation of H3 and H4 histones was attenuated by the LrS, as was the production of TNF-α- and STS-induced proinflammatory cytokines and chemokines. Interestingly, the LrS induced production of macrophage migration inhibitory factor (MIF), a cytokine involved in host-microbe interactions at the gut interface. We propose that the LrS attenuates proinflammatory mediator expression through increased transcription of negative regulators of innate immune activity and changes in global H3 and H4 histone acetylation. To our knowledge, these findings provide novel insights into the complex multifaceted mechanisms of action behind secretome-mediated interdomain communication at the gut-mucosal interface.

Effects of high intensity interval training on cardiorespiratory fitness and salivary levels of IL-8, IL-1ra, and IP-10 in adults with asthma and non-asthma controls.

OBJECTIVE: The purpose of this study was to determine whether high intensity interval training (HIIT) would lead to improvements in 1) maximal VO2, VE, VE/VCO2, and VE/MVV, and/or 2) resting salivary concentrations of pro-inflammatory markers Interleukin (IL-8), interferon-gamma-inducible-protein (CXCL10/IP-10)) and anti-inflammatory marker IL-1 receptor antagonist (IL-1ra) in adults with well-controlled asthma compared to non-asthma controls. METHODS: Participants completed a maximal exercise test at the beginning (T1) and end (T2) of a 6-week HIIT intervention; saliva samples were obtained at the beginning and 30 min following the first (T1) and last (T2) exercise session. RESULTS: Adults with asthma (n = 20; age: 21.4 ± 2.4 years) and non-asthma controls (n = 12; age: 22.5 ± 3.4 years) completed the intervention. VO2max increased from T1 to T2 in both groups (asthma T1 32.9 ± 8, T2 38.6 ± 8.2 ml/kg/min; controls T1 34.5 ± 11.8, T2 38.9 ± 12.3 ml/kg/min). VEmax also increased in both groups (asthma T1 97.7, T2 110.8 units, p < 0.001, hp2 = <0.04; control T1 106.3, T2 118.1, p < 0.001, hp2 0.02). An increase in VE/VCO2 (F(1, 10)=22.11, p = 0.001) and VE/MVV (F(1, 10) = 111.30, p < 0.001) was observed in the control group; no differences were observed in the asthma group. No differences in IL-8 or IL-1ra were observed between groups. In the asthma group, resting salivary IP-10 concentrations significantly decreased from T1 (0.025 pg/ug protein) to T2 (0.015 pg/ug protein, p = 0.039, hp2 = 0.3 (moderate effect)). CONCLUSION: A 6-week HIIT intervention led to a similar increase in VO2max and VEmax in those with and without asthma, and a decrease in resting salivary IP-10 levels among adults with asthma.

From trial to practice: incidence and severity of COVID-19 vaccine side effects in a medically at-risk and vaccine-hesitant community.

BACKGROUND: The rapid authorization and widespread rollout of COVID-19 vaccines in the United States demonstrated a need for additional data on vaccine side effects, both to provide insight into the range and severity of side effects that might be expected in medically-diverse populations as well as to inform decision-making and combat vaccine hesitancy going forward. Here we report the results of a survey of 4825 individuals from southcentral Kentucky who received two doses of either the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) vaccine between December 14, 2020 and May 1, 2021. As new versions of the vaccine are rolled-out, local initiatives such as this may offer a means to combat vaccine hesitancy in reference to COVID-19, but are also important as we face new viral threats that will necessitate a rapid vaccine rollout, and to combat a growing public distrust of vaccines in general. METHODS: Individuals that received two doses of either BNT162b2 or mRNA-1273 between December 14, 2020 and May 1, 2021 were sent a survey, created by the research team. Respondents were asked to rate the incidence and severity of 15 potential side effects and two related outcomes following each of their two doses of the vaccine. All statistical analyses were carried out using SYSTAT, version 13. The data were analyzed utilizing a range of statistical tests, including chi-square tests of association, Cohen's h, Kruskal-Wallis test one-way nonparametric ANOVA, least-squares regression, and Wilcoxon signed-ranks test. Significance was assessed using Bonferroni-adjusted criteria within families of tests. RESULTS: In general, the pattern and severity in side effects was similar to both clinical trial data as well as other published studies. Responses to the mRNA-1273 vaccine were more severe than to BNT162b2, though all were generally in the mild to moderate category. Individuals who reported having previously tested positive for COVID-19 reported stronger responses following the first dose of either vaccine relative to COVID-naïve individuals. The reported severity to the COVID-19 vaccine was positively correlated with self-reported responses to other vaccines. CONCLUSIONS: Our findings allow broad-scale estimates of the nature and severity of reactions one might expect following vaccination within a clinically-diverse community, and provide a context for addressing vaccine hesitancy in communities such as ours, where locally-generated data and communication may be more influential than national trends and statistics in convincing individuals to become vaccinated. Further, we argue this community-based approach could be important in the future in three key ways: 1) as new boosters and modified vaccines re-volatilize vaccine hesitancy, 2) as new vaccines receive similar testing and rapid authorization, and 3) to combat vaccine hesitancy in other arenas (e.g., annual vaccines, childhood vaccines).

Abdominal Wall Thickness at Palmer's Point and Distance to Adjacent Structures across the Body Mass Index Spectrum.

STUDY OBJECTIVE: Studies delineating left upper quadrant (LUQ) anatomy across a range of body mass indices are lacking. We aimed primarily to compare, between nonobese and obese women, abdominal wall thickness and the distance from the LUQ to key structures. In addition, we aimed to characterize LUQ anatomy in underweight women. DESIGN: A retrospective cohort study. SETTING: A tertiary academic medical institution. PATIENTS: Sixty women (30 nonobese, 30 obese) aged 18 years and older who underwent abdominal imaging from October 1, 2018, to December 31, 2018. INTERVENTIONS: Computed tomography imaging of the chest, abdomen, and pelvis. MEASUREMENTS AND MAIN RESULTS: Abdominal wall thickness at the LUQ was significantly greater in obese (4.3 ± 1.7 cm) than nonobese patients (2.4 ± 1.7 cm) (p <.001), as were distances to all key structures (aorta, vena cava, spleen, stomach, pancreas, liver, left kidney, and pelvis) (p ≤.02). On average, all structures, with the exception of stomach and liver, were >10 cm (the length of a typical insufflation needle) away from the LUQ insertion point in obese women. In underweight women, the aorta, spleen, stomach, pancreas, and liver were all within 10 cm of the LUQ insertion point. Within the obese and nonobese group, abdominal wall thickness at the LUQ was significantly greater than at the umbilicus (p <.001). Body mass index was more strongly correlated with abdominal wall thickness at the LUQ (r = 0.84; p <.001) than at the umbilicus (r = 0.69; p <.001) (p = .007 for comparison). CONCLUSION: This study highlights special anatomic considerations for LUQ access in obese and underweight patients. In obese women, abdominal wall thickness may be greater at this site than at the umbilicus and the liver and stomach remain within reach of an insufflation needle. The increased working distance from the LUQ to the pelvis in obese patients may necessitate specialized instruments if this site is used during surgery. In underweight women, the aorta, in addition to many other structures, is within reach of commonly used entry devices.

Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and α-Synucleinopathy Reveals Age- and Disease-Related Differences.

Here, we utilize the stability of proteins from rates of oxidation (SPROX) technique, to profile the thermodynamic stabilities of proteins in brain tissue cell lysates from Huα-Syn(A53T) transgenic mice at three time points including at 1 month (n = 9), at 6 months (n = 7), and at the time (between 9 and 16 months) a mouse became symptomatic (n = 8). The thermodynamic stability profiles generated here on 332 proteins were compared to thermodynamic stability profiles generated on the same proteins from similarly aged wild-type mice using a two-way unbalanced analysis of variance (ANOVA) analysis. This analysis identified a group of 22 proteins with age-related protein stability changes and a group of 11 proteins that were differentially stabilized in the Huα-Syn(A53T) transgenic mouse model. A total of 9 of the 11 proteins identified here with disease-related stability changes have been previously detected in human cerebral spinal fluid and thus have potential utility as biomarkers of Parkinson's disease (PD). The differential stability observed for one protein, glutamate decarboxylase 2 (Gad2), with an age-related change in stability, was consistent with the differential presence of a known, age-related truncation product of this protein, which is shown here to have a higher folding stability than full-length Gad2. Mass spectrometry data were deposited at ProteomeXchange (PXD016985).

High Burden of Bloodstream Infections Associated With Antimicrobial Resistance and Mortality in the Neonatal Intensive Care Unit in Pune, India.

BACKGROUND: Antimicrobial resistance (AMR) is a growing threat to newborns in low- and middle-income countries (LMIC). METHODS: We performed a prospective cohort study in 3 tertiary neonatal intensive care units (NICUs) in Pune, India, to describe the epidemiology of neonatal bloodstream infections (BSIs). All neonates admitted to the NICU were enrolled. The primary outcome was BSI, defined as positive blood culture. Early-onset BSI was defined as BSI on day of life (DOL) 0-2 and late-onset BSI on DOL 3 or later. RESULTS: From 1 May 2017 until 30 April 2018, 4073 neonates were enrolled. Among at-risk neonates, 55 (1.6%) developed early-onset BSI and 176 (5.5%) developed late-onset BSI. The majority of BSIs were caused by gram-negative bacteria (GNB; 58%); among GNB, 61 (45%) were resistant to carbapenems. Klebsiella spp. (n = 53, 23%) were the most common cause of BSI. Compared with neonates without BSI, all-cause mortality was higher among neonates with early-onset BSI (31% vs 10%, P < .001) and late-onset BSI (24% vs 7%, P < .001). Non-low-birth-weight neonates with late-onset BSI had the greatest excess in mortality (22% vs 3%, P < .001). CONCLUSIONS: In our cohort, neonatal BSIs were most commonly caused by GNB, with a high prevalence of AMR, and were associated with high mortality, even in term neonates. Effective interventions are urgently needed to reduce the burden of BSI and death due to AMR GNB in hospitalized neonates in LMIC.

Community-Onset Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Young Infants: A Systematic Review.

OBJECTIVE: To summarize and evaluate current reports on community-onset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young infants. STUDY DESIGN: We performed a systematic review to identify reports published from November 1, 2019, until June 15, 2020, on laboratory-confirmed community-onset SARS-CoV-2 infection in infants younger than 3 months of age. We excluded studies reporting neonates with perinatal coronavirus disease 2019 (COVID-19) exposure and diagnosis before hospital discharge and hospital-onset disease, as well as clinically diagnosed cases without confirmation. Two independent reviewers performed study screening, data abstraction, and risk of bias assessment. Variables of interest included patient age, exposure to COVID-19, medical history, clinical symptoms, SARS-CoV-2 testing, laboratory findings, clinical course, and disposition. RESULTS: In total, 38 publications met inclusion criteria, including 23 single case reports, 14 case series, and 1 cohort study, describing 63 infants younger than 3 months of age with laboratory-confirmed SARS-CoV-2 infection. Most cases were mild to moderate. Fever, respiratory, gastrointestinal, cardiac, and neurologic findings were reported. Laboratory abnormalities included neutropenia, lymphopenia, and elevated serum levels of inflammatory markers and aminotransferases. Fifty-eight (92%) infants were hospitalized, 13 (21%) were admitted to the intensive care unit, and 2 (3%) required mechanical ventilation. No death was reported. CONCLUSIONS: Among young infants with laboratory-confirmed SARS-CoV-2 infection, most cases were mild to moderate and improved with supportive care. Our results demonstrate a need for a high index of suspicion for SARS-CoV-2 infection in young infants presenting with generalized symptoms such as fever or decreased feeding, even in the absence of respiratory symptoms.

Drooling in Parkinson's Disease: Prevalence and Progression from the Non-motor International Longitudinal Study.

Sialorrhoea in Parkinson's disease (PD) is an often neglected yet key non-motor symptom with impact on patient quality of life. However, previous studies have shown a broad range of prevalence figures. To assess prevalence of drooling in PD and its relationship to quality of life, we performed a retrospective analysis of 728 consecutive PD patients who had a baseline and follow-up assessment as part of the Non-motor International Longitudinal Study (NILS), and for whom drooling presence and severity were available, assessed through the Non-Motor Symptoms Scale (NMSS). In addition, we analysed the prevalence of associated dysphagia through self-reported outcomes. Quality of life was assessed through the PDQ-8 scale. Baseline (disease duration 5.6 years) prevalence of drooling was 37.2% (score ≥ 1 NMSS question 19), and after 3.27 ± 1.74 years follow-up, this was 40.1% (p = 0.17). The prevalence of drooling increased with age (p < 0.001). The severity of drooling, however, did not change (p = 0.12). While in 456 patients without drooling at baseline, only 16% (n = 73) had dysphagia (question 20 of the NMSS), in those with drooling this was 34.3% (p < 0.001). At follow-up, the number of patients with dysphagia had increased, 20.4% with no drooling had dysphagia, and 43.6% with drooling had dysphagia. Both at baseline and follow-up, drooling severity was significantly positively associated with quality of life (PDQ-8; r = 0.199; p < 0.001). In moderately advanced PD patients, subjective drooling occurs in over one-third of patients and was significantly associated with decreased quality of life. Dysphagia occurred significantly more often in patients with drooling.

Proteome-Wide Structural Biology: An Emerging Field for the Structural Analysis of Proteins on the Proteomic Scale.

Over the past decade, a suite of new mass-spectrometry-based proteomics methods has been developed that now enables the conformational properties of proteins and protein-ligand complexes to be studied in complex biological mixtures, from cell lysates to intact cells. Highlighted here are seven of the techniques in this new toolbox. These techniques include chemical cross-linking (XL-MS), hydroxyl radical footprinting (HRF), Drug Affinity Responsive Target Stability (DARTS), Limited Proteolysis (LiP), Pulse Proteolysis (PP), Stability of Proteins from Rates of Oxidation (SPROX), and Thermal Proteome Profiling (TPP). The above techniques all rely on conventional bottom-up proteomics strategies for peptide sequencing and protein identification. However, they have required the development of unconventional proteomic data analysis strategies. Discussed here are the current technical challenges associated with these different data analysis strategies as well as the relative analytical capabilities of the different techniques. The new biophysical capabilities that the above techniques bring to bear on proteomic research are also highlighted in the context of several different application areas in which these techniques have been used, including the study of protein ligand binding interactions (e.g., protein target discovery studies and protein interaction network analyses) and the characterization of biological states.

The perpetual state of emergency that sacrifices protected areas in a changing climate.

A modern challenge for conservation biology is to assess the consequences of policies that adhere to assumptions of stationarity (e.g., historic norms) in an era of global environmental change. Such policies may result in unexpected and surprising levels of mitigation given future climate-change trajectories, especially as agriculture looks to protected areas to buffer against production losses during periods of environmental extremes. We assessed the potential impact of climate-change scenarios on the rates at which grasslands enrolled in the Conservation Reserve Program (CRP) are authorized for emergency harvesting (i.e., biomass removal) for agricultural use, which can occur when precipitation for the previous 4 months is below 40% of the normal or historical mean precipitation for that 4-month period. We developed and analyzed scenarios under the condition that policy will continue to operate under assumptions of stationarity, thereby authorizing emergency biomass harvesting solely as a function of precipitation departure from historic norms. Model projections showed the historical likelihood of authorizing emergency biomass harvesting in any given year in the northern Great Plains was 33.28% based on long-term weather records. Emergency biomass harvesting became the norm (>50% of years) in the scenario that reflected continued increases in emissions and a decrease in growing-season precipitation, and areas in the Great Plains with higher historical mean annual rainfall were disproportionately affected and were subject to a greater increase in emergency biomass removal. Emergency biomass harvesting decreased only in the scenario with rapid reductions in emissions. Our scenario-impact analysis indicated that biomass from lands enrolled in the CRP would be used primarily as a buffer for agriculture in an era of climatic change unless policy guidelines are adapted or climate-change projections significantly depart from the current consensus.

Drug-resistant Enterobacteriaceae colonization is associated with healthcare utilization and antimicrobial use among inpatients in Pune, India.

BACKGROUND: Healthcare exposure may increase drug-resistant Enterobacteriaceae colonization risk. Nascent antimicrobial stewardship efforts in low- and middle-income countries require setting-specific data. We aimed to evaluate risk factors for inpatient drug resistant Enterobacteriaceae colonization in a resource-limited setting in India. METHODS: Patients age ≥ 6 months admitted with ≥24 h of fever to a tertiary hospital in Pune, India were enrolled in a prospective cohort. Perirectal swabs, collected on admission and hospitalization day 3 or 4, were cultured in vancomycin- and ceftriaxone-impregnated media to assess for ceftriaxone-resistant Enterobacteriaceae (CTRE) and carbapenem-resistant Enterobacteriaceae (CPRE). Multivariable analyses assessed risk factors for drug-resistant Enterobacteriaceae colonization among participants without admission colonization. RESULTS: Admission perirectal swabs were collected on 897 participants; 87 (10%) had CTRE and 14 (1.6%) had CPRE colonization. Admission CTRE colonization was associated with recent healthcare contact (p < 0.01). Follow-up samples were collected from 620 participants, 67 (11%) had CTRE and 21 (3.4%) had CPRE colonization. Among 561 participants without enrollment CTRE colonization, 49 (9%) participants were colonized with CTRE at follow-up. Detection of CTRE colonization among participants not colonized with CTRE at admission was independently associated with empiric third generation cephalosporin treatment (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.8). Follow-up transition to CPRE colonization detection was associated with ICU admission (OR 3.0, 95% CI 1.0-8.5). CONCLUSIONS: Patients who receive empiric third generation cephalosporins and are admitted to the ICU rapidly develop detectable CTRE and CPRE colonization. Improved antimicrobial stewardship and infection control measures are urgently needed upon hospital admission.

The Relative Effects of Artemether-lumefantrine and Non-artemisinin Antimalarials on Gametocyte Carriage and Transmission of Plasmodium falciparum: A Systematic Review and Meta-analysis.

BACKGROUND: Artemisinin-based combination therapies (ACTs) have been widely adopted as first-line agents to treat uncomplicated falciparum malaria due to their activity against multidrug resistant parasites. ACTs may also disrupt transmission through a direct antigametocyte effect, but the extent of this effect is uncertain. We assessed the evidence for and estimated the effects of the most widely-deployed ACT, artemether-lumefantrine (AL), relative to non-ACTs on gametocyte clearance and transmission interruption. METHODS: We searched electronic databases for randomized controlled trials comparing AL to non-ACTs that reported gametocyte counts or results of mosquito-feeding assays. Two authors working independently assessed eligibility, extracted data, and evaluated the risk of bias. We conducted meta-analyses using a random-effects model. RESULTS: We identified 22 eligible trials. The pooled odds of gametocytemia at 1 week were lower in AL- compared to non-ACT-treated participants (odds ratio [OR] 0.09; 95% confidence interval [CI], 0.06-0.15; I2 = 0.60, P < .01; 15 trials). The odds of transmission to mosquitoes were also lower in AL treatment groups (OR 0.06; 95% CI, 0.00-0.47, P < .01 at 7 days post-treatment; 1 trial; OR 0.56; 95% CI, 0.36-0.88, P = .01 at 14 days post-treatment; 1 trial). CONCLUSION: AL is superior to non-ACTs in reducing gametocytemia, and, based on limited evidence, abating transmission to mosquitoes. The transmission-limiting benefit of AL has relevance for policymakers planning optimal utilization of control strategies, including use of ACTs for malaria treatment and chemoprevention.

Outbreaks in the neonatal ICU: a review of the literature.

PURPOSE OF REVIEW: Neonates in the neonatal ICU (NICU) are uniquely vulnerable to colonization and infection with pathogens such as multidrug resistant Gram-negative bacteria, which in turn are associated with increased infection-related morbidities and higher case-fatality rates. We reviewed the English, French, and German language literature published between 2015 and 2017, for reports of NICU outbreaks. RECENT FINDINGS: A total of 39 outbreaks in NICUs were reported with Gram-negative bacteria (n = 21; 54%) causing most, and extended spectrum beta-lactamase-producing organisms being the most frequent resistance mechanism reported (n = 5). Five viral outbreaks were reported (respiratory syncytial virus = 3). A significant proportion of outbreaks (33%) did not identify a source. Whole genome sequencing was used more (n = 6 reports). The most common described infection prevention and control interventions included staff and parent education on hand hygiene, patient isolation, additional contact precautions, including discontinuation of 'kangaroo care', and cohorting. Reporting and publication bias are likely common. SUMMARY: NICUs must be vigilant in identifying outbreaks, conduct comprehensive investigations, and implement targeted infection prevention and control strategies. Molecular epidemiology capacities are an essential element in outbreak investigation. More studies are needed to determine the added value of active colonization screening and their impact on outbreak development.

Impact of ß2-1 fructan on faecal community change: results from a placebo-controlled, randomised, double-blinded, cross-over study in healthy adults.

Healthy adults (n 30) participated in a placebo-controlled, randomised, double-blinded, cross-over study consisting of two 28 d treatments (ß2-1 fructan or maltodextrin; 3×5 g/d) separated by a 14-d washout. Subjects provided 1 d faecal collections at days 0 and 28 of each treatment. The ability of faecal bacteria to metabolise ß2-1 fructan was common; eighty-seven species (thirty genera, and four phyla) were isolated using anaerobic medium containing ß2-1 fructan as the sole carbohydrate source. ß2-1 fructan altered the faecal community as determined through analysis of terminal restriction fragment length polymorphisms and 16S rRNA genes. Supplementation with ß2-1 fructan reduced faecal community richness, and two patterns of community change were observed. In most subjects, ß2-1 fructan reduced the content of phylotypes aligning within the Bacteroides, whereas increasing those aligning within bifidobacteria, Faecalibacterium and the family Lachnospiraceae. In the remaining subjects, supplementation increased the abundance of Bacteroidetes and to a lesser extent bifidobacteria, accompanied by decreases within the Faecalibacterium and family Lachnospiraceae. ß2-1 Fructan had no impact on the metagenome or glycoside hydrolase profiles in faeces from four subjects. Few relationships were found between the faecal bacterial community and various host parameters; Bacteroidetes content correlated with faecal propionate, subjects whose faecal community contained higher Bacteroidetes produced more caproic acid independent of treatment, and subjects having lower faecal Bacteroidetes exhibited increased concentrations of serum lipopolysaccharide and lipopolysaccharide binding protein independent of treatment. We found no evidence to support a defined health benefit for the use of ß2-1 fructans in healthy subjects.

Peripheral nerve injury induces persistent vascular dysfunction and endoneurial hypoxia, contributing to the genesis of neuropathic pain.

Nerve injury is associated with microvascular disturbance; however, the role of the vascular system has not been well characterized in the context of neuropathic pain. Furthermore, ischemia is thought to play a role in a number of neuropathic pain conditions, and yet the role of hypoxia has also not been characterized in neuropathic pain conditions. In this study, we observed the presence of persistent endoneurial hypoxia in a mouse model of traumatic peripheral nerve injury, causing painful mononeuropathy. We attribute the ongoing hypoxia to microvascular dysfunction, endoneurial fibrosis, and increased metabolic requirements within the injured nerve. Increased lactate levels were observed in injured nerves, as well as increased oxygen consumption and extracellular acidification rates, suggesting that anaerobic glycolysis is required to maintain cellular ATP levels. Hypoxia causes a reduction in levels of the Na(+)/K(+) ATPase ion transporter in both cultured primary dorsal root ganglion neurons and injured peripheral nerve. A reduction of Na(+)/K(+) ATPase ion transporter levels likely contributes to the hyperexcitability of injured nerves. Physiological antagonism of hypoxia with hyperbaric oxygen alleviated mechanical allodynia in nerve-injured animals. These results suggest that hypoxia and the Na(+)/K(+) ATPase ion transporter may be a novel mechanistic target for the treatment of neuropathic pain. In addition, the findings support the possibility of using hypoxia activated pro-drugs to localize treatments for neuropathic pain and nerve injury to injured nerves.