Early-life prefrontal cortex inhibition and early-life stress lead to long-lasting behavioral, transcriptional, and physiological impairments.

Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex (PFC) activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling. Here we test whether changes in PFC activity during early life affect the developing cortex leading to behavioral alterations in the adult. We show that inhibiting the PFC of mouse pups leads to cognitive deficits in the adult comparable to those seen following maternal separation. Moreover, we show that activating the PFC during maternal separation can prevent these behavioral deficits. To test how maternal separation affects the transcriptional profile of the PFC we performed single-nucleus RNA-sequencing. Maternal separation led to differential gene expression almost exclusively in inhibitory neurons. Among others, we found changes in GABAergic and serotonergic pathways in these interneurons. Interestingly, both maternal separation and early-life PFC inhibition led to changes in physiological responses in prefrontal activity to GABAergic and serotonergic antagonists that were similar to the responses of more immature brains. Prefrontal activation during maternal separation prevented these changes. These data point to a crucial role of PFC activity during early life in behavioral expression in adulthood.

A tuberculosis elimination-focused geospatial approach to optimising access to diagnostic GeneXpert machines in Fiji.

OBJECTIVES: Fiji could be the first country to eliminate tuberculosis. To inform this strategy, we aimed to identify how many GeneXpert® machines are required to enable over 90% of Fijians to be within one-hour easy access. METHODS: We used Geographic Information System (Quantum GIS; QGIS), OpenStreetMap and population data (Kontur) to map possible facilities in relation to QGIS generated 60-min drive-time isochrones, with correction for missing road data. For outer islands, we calculated a distance to nearest hub operation. RESULTS: The solution comprised 24 GeneXpert® machines, allocating 7 GeneXpert® to Viti Levu, 6 GeneXpert® to Vanua Levu and 11 to other islands. This resulted in 827,810 people, 93.6% of Fiji's population, being within 1 h of a machine. Twenty-one thousand four hundred seventy-nine people on outer islands were an average of 43 km by water from the nearest facility. CONCLUSIONS: We conclude that over 90% of Fijians could be within an hour of a GeneXpert® machine with placement of 24 machines.

Developmental alcohol exposure is exhausting: Sleep and the enduring consequences of alcohol exposure during development.

Prenatal alcohol exposure is the leading nongenetic cause of human intellectual impairment. The long-term impacts of prenatal alcohol exposure on health and well-being are diverse, including neuropathology leading to behavioral, cognitive, and emotional impairments. Additionally negative effects also occur on the physiological level, such as the endocrine, cardiovascular, and immune systems. Among these diverse impacts is sleep disruption. In this review, we describe how prenatal alcohol exposure affects sleep, and potential mechanisms of those effects. Furthermore, we outline the evidence that sleep disruption across the lifespan may be a mediator of some cognitive and behavioral impacts of developmental alcohol exposure, and thus may represent a promising target for treatment.

Evaluating Outcome Prediction via Baseline, End-of-Treatment, and Delta Radiomics on PET-CT Images of Primary Mediastinal Large B-Cell Lymphoma.

OBJECTIVES: Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression (TTP) of primary mediastinal large B-cell lymphoma (PMBCL) patients. MATERIAL AND METHODS: Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans. Consequently, our radiomics analysis focused on these 31 patients who underwent [18F]FDG PET-CT scans before and after R-CHOP chemotherapy. Expert manual lesion segmentation was conducted on their scans for delta radiomics analysis, along with an additional 19 EoT scans, totaling 50 segmented scans for single time point analysis. Radiomics features (on PET and CT), along with maximum and mean standardized uptake values (SUVmax and SUVmean), total metabolic tumor volume (TMTV), tumor dissemination (Dmax), total lesion glycolysis (TLG), and the area under the curve of cumulative standardized uptake value-volume histogram (AUC-CSH) were calculated. We additionally applied longitudinal analysis using radial mean intensity (RIM) changes. For prediction of relapse/progression, we utilized the individual coefficient approximation for risk estimation (ICARE) and machine learning (ML) techniques (K-Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA), and Random Forest (RF)) including sequential feature selection (SFS) following correlation analysis for feature selection. For TTP, ICARE and CoxNet approaches were utilized. In all models, we used nested cross-validation (CV) (with 10 outer folds and 5 repetitions, along with 5 inner folds and 20 repetitions) after balancing the dataset using Synthetic Minority Oversampling TEchnique (SMOTE). RESULTS: To predict relapse/progression using Delta radiomics between the baseline (staging) and EoT scans, the best performances in terms of accuracy and F1 score (F1 score is the harmonic mean of precision and recall, where precision is the ratio of true positives to the sum of true positives and false positives, and recall is the ratio of true positives to the sum of true positives and false negatives) were achieved with ICARE (accuracy = 0.81 ± 0.15, F1 = 0.77 ± 0.18), RF (accuracy = 0.89 ± 0.04, F1 = 0.87 ± 0.04), and LDA (accuracy = 0.89 ± 0.03, F1 = 0.89 ± 0.03), that are higher compared to the predictive power achieved by using only EoT radiomics features. For the second category of our analysis, TTP prediction, the best performer was CoxNet (LASSO feature selection) with c-index = 0.67 ± 0.06 when using baseline + Delta features (inclusion of both baseline and Delta features). The TTP results via Delta radiomics were comparable to the use of radiomics features extracted from EoT scans for TTP analysis (c-index = 0.68 ± 0.09) using CoxNet (with SFS). The performance of Deauville Score (DS) for TTP was c-index = 0.66 ± 0.09 for n = 50 and 0.67 ± 03 for n = 31 cases when using EoT scans with no significant differences compared to the radiomics signature from either EoT scans or baseline + Delta features (p-value> 0.05). CONCLUSION: This work demonstrates the potential of Delta radiomics and the importance of using EoT scans to predict progression and TTP from PMBCL [18F]FDG PET-CT scans.

Molecular and clinical epidemiology of carbapenem resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales in Fiji: a multicentre prospective observational study.

Background: Carbapenem resistant organisms (CROs) such as Acinetobacter baumannii (CRAb), Pseudomonas aeruginosa (CRPa), Escherichia coli (CREc), and Klebsiella pneumoniae (CRKp) have been identified by the World Health Organization (WHO) as global priority pathogens. The dissemination of these pathogens and clonal outbreaks within healthcare facilities are of serious concern, particularly in regions with limited resources. In Fiji, where healthcare services are primarily provided by public hospitals, understanding the extent and nature of this problem is essential for the development of effective patient management, prevention interventions and control strategies. Methods: CROs isolated from 211 (77.3%) non-sterile (urinary catheters, urine, sputum, wound swab, and endotracheal tube) and 62 (22.7%) normally sterile (blood, cerebrospinal fluid, intravascular catheter, and aspirates) body sites of 272 patients treated at the three major hospitals in Fiji, the Colonial War Memorial Hospital (CWMH), Lautoka Hospital (LTKH), and Labasa Hospital (LBSH), and outer peripheral health centres around Fiji, were analysed. Clinical and demographic patient data such as age, sex, admission diagnosis, admission and discharge dates, patient outcomes, date of death, start and end date of meropenem and colistin treatment were reviewed. These CRO isolates comprised A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae, that were prospectively collected at the microbiology laboratory of CWMH and LBSH from January 2020 through August 2021 and at the LTKH from January 2020 to December 2021. In addition, 10 retrospectively stored CRPa isolates collected from patients at the CWMH from January through December 2019, were also included in the study. All isolates were characterised using mass spectrometry, antimicrobial susceptibility testing, and whole genome sequencing. Phylogenetic relationships among the CROs were assessed through core genome single nucleotide polymorphism (SNP) analysis. The CRAb isolates were also compared to the CRAb isolates from CWMH isolated in 2016/2017 and 2019, along with CRAb isolates obtained from Fijian patients admitted to New Zealand hospitals in 2020 and 2021 from our retrospective study. Findings: Of 272 patients, 140 (51.5%) were male, the median (range) age of patients was 45 (<1-89) years, 161 (59.2%) were I-Taukei, 104 (38.2%) Fijians of Indian descent, and 7 (2.6%) were from other ethnic backgrounds. 234 (86.0%) of these 272 patients, had their first positive CRO sample collected ≥72 h following admission and the remaining 38 (14.0%) were isolated within 72 h following admission. Of the 273 CROs, 146 (53.5%) were collected at the CWMH, 66 (24.2%) LTKH, and 61 (22.3%) LBSH, while 62 (22.7%) were isolated from normally sterile sites and 211 (77.3%) from sites that are not sterile. Of 273 isolates, 131 (48.0%) were CRAb, 90 (33.0%) CRPa, 46 (16.8%) CREc, and 6 (2.2%) CRKp. Of 131 CRAb, 108 (82.4%) were ST2, with three distinct clones, all encoding bla OXA-23 and bla OXA - 66, while clone 3 also encoded bla NDM-1; bla OXA-23 was associated with two copies of ISAba1 insertion element, forming the composite transposon Tn2006. The first two CRAb ST2 clones were genetically linked to those isolated at CMWH 2016 through 2019, while the third was genetically linked to isolates from Fijian patients admitted to New Zealand hospitals in 2020 and 2021. Of CRPa, 65 (72.2%) were ST773 and carried ß-lactamase genes bla NDM-1, bla OXA-50, and bla OXA-395. Of 10 retrospective CRPa isolates, all belonged to CRPa ST773 and carried bla NDM-1, bla OXA-50, and bla OXA-395. Of 46 CREc, 44 (95.7%) were ST410 and encoded bla NDM-7 on an IncX3 plasmid. Of 6 CRKp, 4 (66.7%) were ST16 and carried bla NDM-5 on an IncX3 plasmid. Other sequence types of CRPa (ST9, ST357, ST654, ST664), CRAb (ST25, ST374, ST499), CREc (ST167), and CRKp (ST45, ST336) were also detected. Of those receiving meropenem treatment in the prospective study, 30 (57.7%) received it inappropriately. Of 272 patients, 65 (23.9%) died within the 30 days after first positive CRO isolation. Interpretation: We identified nosocomial transmission of distinct clones of CRAb ST2, CRPa ST773, CREc ST410, and CRKp ST16 within and between the three major hospitals in Fiji. Moreover, community onset infections associated with CRPa, CREc, and CRAb were also detected. Of note, cross-border transmission of CRAb ST2 clone 3 strain between Fiji and New Zealand was also detected. These clones encoded an array of carbapenem resistance genes associated with mobile genetic elements, including plasmids, transposons, and integrative and conjugative elements, signifying their potential for increased mobility, further acquisition of resistance genes, and spread. Inappropriate use of meropenem was common. Of note, the majority of patients who died had acquired CRO during their hospital stay. These findings highlight the need for stringent IPC strategies focusing on catheter and ventilator management, meticulous wound care, rigorous sepsis control, consistent hand hygiene, effective use of disinfectants, and thorough sanitisation of both hospital environments and medical equipment in the three major hospitals in Fiji. Additionally, diligent surveillance of AMR and robust antimicrobial stewardship are crucial for effectively managing nosocomial infections. Funding: This project was funded by the Otago Medical School Foundations Trust (Dean's Bequest Fund) and a Fiji National University seed grant. The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Devaluation of response-produced safety signals reveals circuits for goal-directed versus habitual avoidance in dorsal striatum.

Active avoidance responses (ARs) are instrumental behaviors that prevent harm. Adaptive ARs may contribute to active coping, whereas maladaptive avoidance habits are implicated in anxiety and obsessive-compulsive disorders. The AR learning mechanism has remained elusive, as successful avoidance trials produce no obvious reinforcer. We used a novel outcome-devaluation procedure in rats to show that ARs are positively reinforced by response-produced feedback (FB) cues that develop into safety signals during training. Males were sensitive to FB-devaluation after moderate training, but not overtraining, consistent with a transition from goal-directed to habitual avoidance. Using chemogenetics and FB-devaluation, we also show that goal-directed vs. habitual ARs depend on dorsomedial vs. dorsolateral striatum, suggesting a significant overlap between the mechanisms of avoidance and rewarded instrumental behavior. Females were insensitive to FB-devaluation due to a remarkable context-dependence of counterconditioning. However, degrading the AR-FB contingency suggests that both sexes rely on safety signals to perform goal-directed ARs.

An assessment of latrine front-end characteristics and associated surface E. coli indicated faecal contamination in rural Fiji.

In Fiji, 90% of the population has access to basic sanitation; however, there are still persistent health risks from endemic faecal-oral diseases such as typhoid fever. There is a need to assess the contribution of existing sanitation facilities in the faecal pathogen transmission pathway. This study was conducted as part of a larger planetary health study across 29 rural communities within five river catchments. This specific research aimed to characterise latrine front-ends, both infrastructure and usage behaviour, and to assess the faecal contamination levels on various frequently contacted latrine surfaces in rural Fiji. A sanitation survey, along with observation and latrine swab sampling, was conducted in households over three phases: baseline (n = 311) (Aug-Dec 2019), endline (n = 262) (Jun-Sep 2022) and an in-depth front-end study (n = 12) (Oct-Nov 2022). Of 311 households, almost all had pedestal-type latrines, predominately cistern-flush (83%), followed by pour-flush (13%), and then hole-type (pit) latrines (4%). Washable latrine floors had significantly higher E. coli densities (6.7 × 102 CFU/25 cm2) compared to non-washable floors (1.3 × 102 CFU/25 cm2) (p = 0.05), despite washable floors indicating improved latrines. The in-depth front-end analysis found that moist latrine surfaces had significantly elevated E. coli densities (1.2 × 103 CFU/25 cm2) compared to the dry ones (14.3 CFU/25 cm2) (p < 0.001), highlighting the importance of maintaining dry latrine surfaces. Latrine floors and mid-walls were the most frequently contaminated surfaces, emphasising the need to clean and disinfect these surfaces. Only 46% of the households reported always using soap for handwashing after defecation, exacerbating the risk of transmitting faecal pathogens. This study highlights that latrine cleanliness and hygiene are as crucial as latrine infrastructures for the effective disruption of faecal pathogens transmission during latrine use.

Molecular and clinical epidemiology of carbapenem resistant Acinetobacter baumannii ST2 in Oceania: a multicountry cohort study.

Background: Carbapenem resistant Acinetobacter baumannii (CRAb) is categorised by the World Health Organization (WHO) as a pathogen of critical concern. However, little is known about CRAb transmission within the Oceania region. This study addresses this knowledge gap by using molecular epidemiology to characterise the phylogenetic relationships of CRAb isolated in hospitals in Fiji, Samoa, and other countries within the Oceania region including Australia and New Zealand, and India from South Asia. Methods: In this multicountry cohort study, we analysed clinical isolates of CRAb collected from the Colonial War Memorial Hospital (CWMH) in Fiji from January through December 2019 (n = 64) and Tupua Tamasese Mea'ole Hospital (TTMH) in Samoa from November 2017 through June 2021 (n = 32). All isolates were characterised using mass spectrometry, antimicrobial susceptibility testing, and whole-genome sequencing. For CWMH, data were collected on clinical and demographic characteristics of patients with CRAb, duration of hospital stay, mortality and assessing the appropriateness of meropenem use from the treated patients who had CRAb infections. To provide a broader geographical context, CRAb strains from Fiji and Samoa were compared with CRAb sequences from Australia collected in 2016-2018 (n = 22), New Zealand in 2018-2021 (n = 13), and India in 2019 (n = 58), a country which has close medical links with Fiji. Phylogenetic relationships of all these CRAb isolates were determined using differences in core genome SNPs. Findings: Of CRAb isolates, 49 (77%) of 64 from Fiji and all 32 (100%) from Samoa belonged to CRAb sequence type 2 (ST2). All ST2 isolates from both countries harboured blaOXA-23, blaOXA-66 and ampC-2 genes, mediating resistance to ß-lactam antimicrobials, including cephalosporins and carbapenems. The blaOXA-23 gene was associated with two copies of ISAba1 insertion element, forming the composite transposon Tn2006, on the chromosome. Two distinct clusters (group 1 and group 2) of CRAb ST2 were detected in Fiji. The first group shared common ancestral linkage to all CRAb ST2 collected from Fiji's historic outbreak in 2016/2017, Samoa, Australia and 54% of total New Zealand isolates; they formed a single cluster with a median (range) SNP difference of 13 (0-102). The second group shared common ancestral linkage to 3% of the total CRAb ST2 isolated from India. Fifty eight of the 64 patients with CRAb infections at the CWMH had their first positive CRAb sample collected 72 h or more following admission. Meropenem use was deemed inappropriate in 15 (48%) of the 31 patients that received treatment with meropenem in Fiji. Other strains of CRAb ST1, ST25, ST107, and ST1112 were also detected in Fiji. Interpretation: We identified unrecognised outbreaks of CRAb ST2 in Fiji and Samoa that linked to strains in other parts of Oceania and South Asia. The existence of Tn2006, containing the blaOXA-23 and ISAba1 insertion element, within CRAb ST2 from Fiji and Samoa indicates the potential for high mobility and dissemination. This raises concerns about unmitigated prolonged outbreaks of CRAb ST2 in the two major hospitals in Fiji and Samoa. Given the magnitude of this problem, there is a need to re-evaluate the current strategies used for infection prevention and control, antimicrobial stewardship, and public health measures locally and internationally. Moreover, a collaborative approach to AMR surveillance within the Oceania region with technical, management and budgetary support systems is required to prevent introduction and control transmission of these highly problematic strains within the island nation health systems. Funding: This project was funded by an Otago Global Health Institute seed grant and Maurice Wilkins Centre of Research Excellence (CoREs) grant (SC0000169653, RO0000002300).

Valor do corante vital rosa Bengala como auxiliar no diagnóstico de xerose conjuntival em provas de triagem / Value of the vital dye Bengal rose as an aid in the diagnosis of conjunctival xerosis in trial tests

Demonstrou-se o valor do corante vital Rosa Bengala no diagnóstico da xerose conjuntival e determinou-se a prevalência de lesöes oculares devidas à hipovitaminose A. Estudou-se uma amostra representativa (501 crianças) da populaçäo de 3 a 6 anos do Município de Cotía, SP (Brasil). Realizaram-se exames com e sem o uso de Rosa Bengala nas 501 crianças. As positivas para qualquer das técnicas foram submetidas a prova terapêutica (200.000 UI de vitamina A oral). Examinaram-se as córneas com fluoresceína, quando necessário. Realizou-se dosagem de vitamina A pelo método de Carr-Price. Näo se observaram outras lesöes, além de xerose conjuntival. Verificou-se que as prevalências de resultados positivos foram de 10,0% sem Rosa Bengala e 18,2% com o corante. As provas terapêuticas revelaram sensibilidade e especificidade baixas para o exame sem Rosa Bengala (18,5% e 14,3%, respectivamente) e altas para o exame com Rosa Bengala (81,5% e 89,0%, respectivamente), o que o indica como método diagnóstico auxiliar para provas de triagem

Hipovitaminose A em comunidades do Estado de Sao Paulo, Brasil. / Hypovitaminosis A in comunities of the State of Sao Paulo, Brazil

Foram realizados inqueritos nutricionais completos (de consumo de alimentos, bioquimico e clinico) referentes a deficiencia de vitamina A em onze comunidades do Estado de Sao Paulo.O inquerito alimentar mostrou consumo muito baixo de alimentos fontes de vitamina A, tanto de origem animal como vegetal. O inquerito bioquimico mostrou alta prevalencia de niveis plasmaticos de vitamina A classificados como deficiente e baixo. O inquerito clinico mostrou baixos coeficientes de prevalencia para lesoes oculares, principalmente as mais graves. Embora nem a cegueira, nem as lesoes oculares graves constituissem um problema de Saude Publica, a maioria dessas populacoes corria o risco de que tais lesoes viessem a se tornar um problema

Prevalência de hipovitaminose A em pré-escolares de município da área metropolitana de Säo Paulo, Brasil / Prevalence of hypovitaminosis A in preschool children of a municipality of the Metropolitan area of Sao Paulo, Brazil

Foram realizadas dosagens de vitamina A e caroteno plasmáticos em 362 pré-escolares de 3 a 6 anos de idade, residentes na área urbana do município de Cotia, situado a 34 Km de Säo Paulo, SP (Brasil), usando-se amostra representativa. O método utilizado foi o de Carr-Price e os critérios de classificaçäo dos resultados foram propostos pelo "Interdepartmental Committee on Nutrition for National Defense" (ICNND). A prevalência de hipovitaminose A em nível bioquímico foi de 30,2%

Relationship between acute diarrhoea and low plasma levels of vitamin A and retinol binding protein

O objetivo deste trabalho foi avaliar o estado nutricional relativo a vitamina A e a associacao entre diarreia e os niveis plasmaticos de vitamina A e RBP atraves de um estudo transversal. A vitamina A medida pelo metodo de Neeld e Pearson e RBP pela tecnica de imunodifusao radial. Foram estudadas 78 criancas (com idades entre 18 e 119 meses), 26 com diarreia e 52 como controles, atendidas na consulta ambulatorial do Hospital Santa Casa de Misericordia de Sao Paulo, da cidade de Sao Paulo...

Dislipidemias e alguns fatores de risco associados em uma populaçäo periférica da Regiäo Metropolitana de Säo Paulo, SP-Brasil: um estudo piloto / Lipemic disorders and some associated risk factors in a population on the outs kirts of Greater S.Paulo, SP-Brazil

Realizou-se levantamento da prevalência de dislipidemias e alguns fatores de risco (hipertensäo, obesidade e alcoolismo), em uma populaçäo típica da periferia do Município de Säo Paulo, SP (Brasil). A prevalência de um ou mais fatores de risco foi maior do que 50% em todos os grupos etários. No que concerne às dislipidemias propriamente ditas, foi de aproximadamente 49%, 58% e 57% nos grupos etários de 20 a 39 anos, 40 a 59 anos e 60 anos e mais, respectivamente. A dislipidemia mais frequênte foi devido a baixos níveis de HDL-colesterol, principalmente nos mais jovens, entre 29 e 39 anos. Nos outros dois grupos etários houve prevalência maior de "outras dislipidemias". A obesidade isolada ou associada foi o fator de risco mais relevante na populaçäo estudada. Levanta-se a hipótese de que as dislipidemias podem constituir-se em grave problema de Saúde Pública nas populaçöes periféricas da cidade de Säo Paulo

Riboflavina / Ribofavin

Aborda a riboflavina, suas propriedades, ocorrência em alimentos, efeito do processamento de alimentos, necessidades diárias, absorçäo, transporte e excreçäo, e aspectos clínicos

Distúrbios da nutriçäo

Aborda a vitamina A, suas fórmulas, nomenclaturas e atividade, ocorrência e efeito do processamento de alimentos, metabolismo, necessidades diárias, aspectos clínicos