Iodinated NanoClusters as an inhaled CT contrast agent for lung visualization

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Impact of Maternal Malnutrition on Gut Barrier Defense: Implications for Pregnancy Health and Fetal Development

Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high fat diet (HF). At day 18.5 (term = 19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin (Muc2) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9, associated with reduced expression of maturation markers (Cdx2, Muc2), and increased expression of tight junctions (TJ; Cldn-7). HF fetuses had increased mRNA expression of EGC markers (S100b, Bfabp, Plp1), AMP (Lyz1, Defa1, Reg3g), and TJ (Cldn-3, Cldn-7), and reduced expression of an AMP-activator (Tlr4). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function

Does in utero HIV exposure and the early nutritional environment influence infant development and immune outcomes? Findings from a pilot study in Pretoria, South Africa

BACKGROUND : As mother-to-child transmission of HIV decreases, and the population of infants who are born HIV-exposed, but uninfected (HEU) continues to rise, there is a growing need to understand the development and health outcomes of infants who are HEU to ensure that they have the healthiest start to life. METHODS : In a prospective cohort pilot study at Kalafong Hospital, Pretoria, South Africa, we aimed to determine if we could recruit new mothers living with HIV on antiretrovirals (ART; n = 20) and not on ART (n = 20) and new mothers without HIV (n = 20) through our clinics to study the effects of HEU on growth and immune- and neurodevelopment in infants in early life, and test the hypothesis that infants who were HEU would have poorer health outcomes compared to infants who were HIV-unexposed, uninfected (HUU). We also undertook exploratory analyses to investigate relationships between the early nutritional environment, food insecurity and infant development. Infant growth, neurodevelopment (Guide for Monitoring Child Development [GMCD]) and levels of monocyte subsets (CD14, CD16 and CCR2 expression [flow cytometry]) were measured in infants at birth and 12 weeks (range 8–16 weeks). RESULTS : We recruited 33 women living with HIV on ART and 22 women living without HIV within 4 days of delivery from June to December 2016. Twenty-one women living with HIV and 10 without HIV returned for a follow-up appointment at 12 weeks postpartum. The high mobility of this population presented major challenges to participant retention. Preliminary analyses revealed lower head circumference and elevated CCR2+ (% and median fluorescence intensity) on monocytes at birth among infants who were HEU compared to HUU. Maternal reports of food insecurity were associated with lower maternal nutrient intakes at 12 weeks postpartum and increased risk of stunting at birth for infants who were HEU, but not infants who were HUU. CONCLUSIONS : Our small feasibility pilot study suggests that HEU may adversely affect infant development, and further, infants who are HEU may be even more vulnerable to the programming effects of suboptimal nutrition in utero and postnatally. This pilot and preliminary analyses have been used to inform our research questions and protocol in our ongoing, full-scale study.Additional file 1: Supplementary Figure S1. Sequential gating approach for the measurement of CCR2 expression by CD14+ monocytes. The sequential gating approached used was as follows: First, the viable (7-AAD negative; region ‘Viable”) cells were identified using a 7-AAD vs SS Log density plot. A “Viable” region was created around the 7-AAD negative cells. Gated on the “Viable”cells, a SSLog vs FS plot was used to capture intact cells in the “E” region. CD14+ monocytes were identified (“CD14+” region) using a CD14 vs SS Log density plot that were gated on viable, intact cells (“E” region). CD14+ monocytes that express CCR2 were quantified using a CD192 (CCR2) vs SS Log plot. The proportion of CD14+/CCR2+ cells were captured in the “CD14+ CCR2+” region. The gating strategy followed to quantify CCR2 expression by CD16+ neutrophils was similar to what was described for CD14+ monocytes, but instead of identifying CD14+ monocytes, CD16+ neutrophils were identified (“CD16+” region) using a CD16 vs SS Log density plot that were gated on viable, intact cells (“E” region). CD16+ neutrophils that express CCR2 were quantified using a CD192 (CCR2) vs SS Log plot. The proportion of CD14+/CCR2+ cells was captured in the “CD16+ CCR2+” region.Additional file 2: Supplementary Figure S2. Sequential gating approach for the measurement of CCR2 expression by monocyte subpopulations. Doublets and debris were removed (Region ‘K’) using a FS Area vs FS Height density plot. A 7-AAD vs SS Log density plot, gated on ‘K’ was used to exclude all non-viable cells. Viable cells were captured in region ‘Viable’. Viable CD14+ monocytes were identified (Region ‘CD14+ Monocytes’) using a CD14 APC vs SS Log density plot. Monocyte sub-populations were identified using a CD16 FITC vs CD14 PE density plot gated on viable, CD14+ monocytes. Four monocyte sub-populations were identified: CD14+/CD16-; CD14++/CD16-; CD14+/CD16+; and CD14++/CD16+. The percentage CCR2+ monocytes present in each of the respective monocyte sub-populations were identified using CD195 (CCR2) PE vs SS Log two-parameter plots gated on the respective subpopulations. The overlay plots within the black bordered square indicates the strategy used to determine CCR2 expression of the different monocyte subsets. The negative/positive staining boundaries were determined based on the negative expression of CCR2 by CD16++/CD14- neutrophils (indicated in red in the overlay plots). The CCR2+ populations are indicated in blue.Additional file 3: Supplementary Figure S3. Maternal intake of estimated average requirements for macronutrients, vitamins and minerals for mothers who report on household food security circumstances. Maternal reports of food insecurity did not associate with intake levels of macronutrients or minerals. Maternal reports of experiencing food runout or inability to afford balanced meals associated with lower intake of vitamin B12 (p=0.01; p=0.04). Many women, irrespective of food security reports, are at risk of inadequate macronutrient, vitamin and mineral intakes. Percent intake of EARs for 36 nutrients were calculated for lactating women 14-18, 19-30 or 31-50 years of age [37]. Calculations for EAR for total protein considered maternal weight at time of dietary recall. Data are % intake of EAR reported in maternal dietary recall for macronutrients, *p<0.05 [ANOVA for normal distribution/ equal variance; Kruskal-Wallis/Wilcoxon test for nonparametric data; or Welch’s test for normal data/unequal variance]). CHO = carbohydrates.Additional file 4: Supplementary Figure S4. Cooccurrence of maternal HIV and food insecurity may increase risk of stunting at birth. Amongst infants whose mothers report worrying about food runout, risk of stunting at birth is greater for HEU compared to HUU infants (e; RR=4.90 [0.76, 31.5], ARD=0.56 [0.17, 0.94], p=0.0498). The red line represents the proportion of infants who had stunting at birth or 12 weeks PP. Mosaic plots are proportion (%) of HUU or HEU infants who have stunting (<-2 SD length-for-age standardised according to WHO child growth standards [28]) at birth and 12 weeks old. HUU = HIV-unexposed, uninfected infant; HEU = HIV-exposed, uninfected infant. RR = Relative risk. ARD = Absolute risk difference.Additional file 5: Supplementary Figure S5. Food insecurity may associate with low attainment of GMCD milestones for HUU and HEU infants. Infants whose mothers reported household food insecurity did not attain 1-3 month GMCD milestones (A, C, E) for receptive language, large movement, relating and response behaviour or play activities, or 3-5 month GMCD milestones (B, D, F) for fine movement or relating and response behaviour in the same proportion as the international standardization sample. Maternal reports of food insecurity did not associate with risk of not attaining all 1-3 month or 3-5 month GMCD milestones (A-F, [p>0.05], Fisher’s exact 2-Tail). Data are proportion (%) of infants who attained all age-appropriate GMCD milestones. The horizontal dotted line represents the GMCD standardised international sample proportion (85%) of infants who attained all milestones in that age category, when they were in that age range. The numbers underneath the bars represent the number of infants attaining all milestones for each milestone. GMCD = Guide for monitoring child development; HUU = HIVunexposed, uninfected infant; HEU = HIVexposed, uninfected infant.Additional file 6: Supplementary Table S1. Flow cytometry reagent list (including lasers and detectors used). Supplementary Table S2. Flow cytometry compensation matrix. Supplementary Table S3. Maternal nutrient intakes from one 24-hour dietary recall for mothers with and without HIV who attended follow up. Supplementary Table S4. Maternal nutrient intake from one 24-hour dietary recall for mothers who report experiencing food insecurity compared to those who do not experience food insecurity.The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER); the Faculty of Science, Carleton University; the Canadian Institutes of Health Research (CIHR); a Canadian Graduate Scholarship-Master’s and a Michael Smith Foreign Study Supplement from CIHR.https://pilotfeasibilitystudies.biomedcentral.comam2021ImmunologyObstetrics and GynaecologyPaediatrics and Child Healt

Offspring of Mothers Fed a High Fat Diet Display Hepatic Cell Cycle Inhibition and Associated Changes in Gene Expression and DNA Methylation

The association between an adverse early life environment and increased susceptibility to later-life metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease is described by the developmental origins of health and disease hypothesis. Employing a rat model of maternal high fat (MHF) nutrition, we recently reported that offspring born to MHF mothers are small at birth and develop a postnatal phenotype that closely resembles that of the human metabolic syndrome. Livers of offspring born to MHF mothers also display a fatty phenotype reflecting hepatic steatosis and characteristics of non-alcoholic fatty liver disease. In the present study we hypothesised that a MHF diet leads to altered regulation of liver development in offspring; a derangement that may be detectable during early postnatal life. Livers were collected at postnatal days 2 (P2) and 27 (P27) from male offspring of control and MHF mothers (n = 8 per group). Cell cycle dynamics, measured by flow cytometry, revealed significant G0/G1 arrest in the livers of P2 offspring born to MHF mothers, associated with an increased expression of the hepatic cell cycle inhibitor Cdkn1a. In P2 livers, Cdkn1a was hypomethylated at specific CpG dinucleotides and first exon in offspring of MHF mothers and was shown to correlate with a demonstrable increase in mRNA expression levels. These modifications at P2 preceded observable reductions in liver weight and liver∶brain weight ratio at P27, but there were no persistent changes in cell cycle dynamics or DNA methylation in MHF offspring at this time. Since Cdkn1a up-regulation has been associated with hepatocyte growth in pathologic states, our data may be suggestive of early hepatic dysfunction in neonates born to high fat fed mothers. It is likely that these offspring are predisposed to long-term hepatic dysfunction

Body mass index and risk of pancreatic cancer in a Chinese population

10.1371/journal.pone.0085149PLoS ONE91-POLN

Adherence to Artemisinin-based Combination Therapy for the Treatment of Malaria: A Systematic Review of the Evidence.

Increasing access to and targeting of artemisinin-based combination therapy (ACT) is a key component of malaria control programmes. To maximize efficacy of ACT and ensure adequate treatment outcomes, patient and caregiver adherence to treatment guidelines is essential. This review summarizes the current evidence base on ACT adherence, including definitions, measurement methods, and associated factors. A systematic search of the published literature was undertaken in November 2012 and updated in April 2013. Bibliographies of manuscripts were also searched and additional references identified. Studies were included if they involved at least one form of ACT and reported an adherence measurement. The search yielded 1,412 records, 37 of which were found to measure adherence to ACT. Methods to measure adherence focused on self-report, pill counts and bioassays with varying definitions for adherence. Most studies only reported whether medication regimens were completed, but did not assess how the treatment was taken by the patient (i.e. timing, frequency and dose). Adherence data were available for four different ACT formulations: artemether-lumefantrine (AL) (range 39-100%), amodiaquine plus artesunate (AQ + AS) (range 48-94%), artesunate plus sulphadoxine-pyrimethamine (AS + SP) (range 39-75%) and artesunate plus mefloquine (AS + MQ) (range 77-95%). Association between demographic factors, such as age, gender, education and socio-economic status and adherence to ACT regimens was not consistent. Some evidence of positive association between adherence and patient age, caregiver education levels, drug preferences, health worker instructions, patient/caregiver knowledge and drug packaging were also observed. This review highlights the weak evidence base on ACT adherence. Results suggest that ACT adherence levels varied substantially between study populations, but comparison between studies was challenging due to differences in study design, definitions, and methods used to measure adherence. Standardising methodologies for both self-report and bioassays used for evaluating adherence of different formulations across diverse contexts would improve the evidence base on ACT adherence and effectiveness; namely, specific and measurable definitions for adherence are needed for both methodologies. Additionally, further studies of the individual factors and barriers associated with non-adherence to ACT are needed in order to make informed policy choices and to improve the delivery of effective malaria treatment

Association of Forced Vital Capacity with the Developmental Gene <i>NCOR2</i>

Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 chi

Pandemic intake questionnaire to improve quality, effectiveness, and efficiency of outpatient neurologic and developmental care at the Kennedy Krieger institute during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic uniquely affects patients with neurologic and developmental disabilities at the Kennedy Krieger Institute. These patients are at increased risk of co-morbidities, increasing their risk of contracting COVID-19. Disruptions in their home and school routines, and restrictions accessing crucial healthcare services has had a significant impact.MethodsA Pandemic Intake questionnaire regarding COVID-19 related medical concerns of guardians of patients was distributed using Qualtrics. Data from May-December 2020 were merged with demographic information of patients from 10 clinics (Center for Autism and Related Disorders (CARD), Neurology, Epigenetics, Neurogenetics, Center for Development and Learning (CDL) Sickle Cell, Spinal Cord, Sturge-Weber syndrome (SWS), Tourette's, and Metabolism). A provider feedback survey was distributed to program directors to assess the effectiveness of this intervention.ResultsAnalysis included responses from 1643 guardians of pediatric patients (mean age 9.5 years, range 0–21.6 years). Guardians of patients in more medically complicated clinics reported perceived increased risk of COVID-19 (p &lt; 0.001) and inability to obtain therapies (p &lt; 0.001) and surgeries (p &lt; 0.001). Guardian responses from CARD had increased reports of worsening behavior (p = 0.01). Providers increased availability of in-person and virtual therapies and visits and made referrals for additional care to address this. In a survey of medical providers, five out of six program directors who received the responses to this survey found this questionnaire helpful in caring for their patients.ConclusionThis quality improvement project successfully implemented a pre-visit questionnaire to quickly assess areas of impact of COVID-19 on patients with neurodevelopmental disorders. During the pandemic, results identified several major areas of impact, including patient populations at increased risk for behavioral changes, sleep and/or disruptions of medical care. Most program directors reported improved patient care as a result