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OBJECTIVE: Given the prevalence of neonatal hearing loss (HL) associated with intrauterine viral exposures, the goal of this study is to provide information on neonatal HL in the context of the COVID-19 pandemic. METHODS: Data were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. 1007 participants completed the newborn hearing screen as part of routine clinical care (COMBO-EHR cohort) and 555 completed the National Survey of Children's Health (NSCH) at 2 and/or 3 years of age for research purposes (COMBO-RSCH cohort). Maternal SARS-CoV-2 infection status during pregnancy was determined through electronic health records and maternal-reported questionnaires. RESULTS: In adjusted multivariate logistic regression models covarying for newborn age at assessment, mode of delivery, and gestational age at delivery, there was no significant association between intrauterine SARS-CoV-2 exposure and newborn hearing screening failure (OR = 1.05, 95% CI = 0.39-2.42, p = 0.91) in the COMBO-EHR cohort. In the COMBO-RSCH cohort, there were similar non-significant associations between intrauterine exposure to SARS-CoV-2 and maternal-reported concern for HL on the NSCH (OR = 1.19 [95% CI = 0.30-4.24], p = 0.79). CONCLUSION: There is no association between intrauterine exposure to SARS-CoV-2 and failed hearing screen in neonates. Similarly, based on the NSCH, there is no association between intrauterine exposure to SARS-CoV-2 and maternal-reported concern for hearing in toddlers. These results offer reassurance given the widespread nature of this pandemic with tens of millions of fetuses having a history of intrauterine exposure. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.
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Importance: Stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown. Objective: To examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings. Design, Setting, and Participants: Data for this cohort study were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. M-CHAT-R scores obtained from children aged 16 to 30 months during routine clinical care at Columbia University Irving Medical Center in New York City were abstracted from electronic health records (EHRs) for children born between January 2018 and September 2021 (COMBO-EHR cohort). Separately, the M-CHAT-R was administered at 18 months for children born between February 2020 and September 2021 through a prospective longitudinal study (COMBO-RSCH cohort). Prenatal pandemic exposure (birth after March 1, 2020) and maternal SARS-CoV-2 status during pregnancy was determined through EHRs. Data were analyzed from March 2022 to June 2024. Exposures: Prenatal exposures to the pandemic milieu and maternal SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was rate of positive M-CHAT-R screenings. For all primary analyses, unadjusted χ2 tests and adjusted logistic regression models were performed. Results: The COMBO-EHR cohort included 1664 children (442 born before the pandemic and 1222 born during the pandemic; 997 SARS-CoV-2 unexposed, 130 SARS-CoV-2 exposed, and 95 with unknown SARS-CoV-2 exposure status), of whom 266 (16.0%) were Black, 991 (59.6%) were Hispanic, 400 (24.0%) were White, 1245 (74.8%) were insured through Medicaid, 880 (52.9%) were male, and 204 (12.3%) were born prematurely. The COMBO-RSCH cohort included 385 children (74 born before the pandemic and 311 born during the pandemic; 201 SARS-CoV-2 unexposed, 101 SARS-CoV-2 exposed, and 9 with unknown SARS-CoV-2 exposure status), of whom 39 (10.1%) were Black, 168 (43.6%) were Hispanic, 157 (40.8%) were White, 161 (41.8%) were insured through Medicaid, 222 (57.7%) were male, and 38 (9.9%) were born prematurely. Prenatal pandemic exposure was not associated with a higher positive M-CHAT-R screening rate in either the COMBO-EHR or COMBO-RSCH cohort. Prenatal exposure to maternal SARS-CoV-2 infection was associated with a lower rate of M-CHAT-R positivity in the COMBO-EHR cohort (12.3% [16 children] vs 24.0% [239 children]; adjusted odds ratio, 0.40; 95% CI, 0.22-0.68; P = .001), but no association was found in the COMBO-RSCH cohort (12.9% [13 children] vs 19.9% [40 children]; adjusted odds ratio, 0.51; 95% CI, 0.24-1.04; P = .07). Conclusions and Relevance: In this cohort study of 2 groups of children with prenatal pandemic exposure and/or exposure to maternal SARS-CoV-2 infection, neither exposure was associated with greater M-CHAT-R positivity.
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Transtorno Autístico , COVID-19 , Efeitos Tardios da Exposição Pré-Natal , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/diagnóstico , Feminino , Gravidez , Masculino , Pré-Escolar , Lactente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Transtorno Autístico/epidemiologia , Transtorno Autístico/diagnóstico , Cidade de Nova Iorque/epidemiologia , Pandemias , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Programas de Rastreamento/métodos , Estudos Prospectivos , Adulto , Estudos Longitudinais , Estudos de CoortesRESUMO
The composition of the human gut microbiome varies tremendously among individuals, making the effects of dietary or treatment interventions difficult to detect and characterize. The consumption of fiber is important for gut health, yet the specific effects of increased fiber intake on the gut microbiome vary across studies. The variation in study outcomes might be due to inter-individual (or inter-population) variation or to the details of the interventions including the types of fiber, length of study, size of cohort, and molecular approaches. Thus, to identify generally (on average) consistent fiber-induced responses in the gut microbiome of healthy individuals, we re-analyzed 16S rRNA sequencing data from 21 dietary fiber interventions from 12 human studies, which included 2,564 fecal samples from 538 subjects across all interventions. Short-term increases in dietary fiber consumption resulted in highly consistent gut bacterial community responses across studies. Increased fiber consumption explained an average of 1.5% of compositional variation (vs 82% of variation attributed to the individual), reduced alpha-diversity, and resulted in phylogenetically conserved responses in relative abundances among bacterial taxa. Additionally, we identified bacterial clades, at approximately the genus level, that were highly consistent in their response (on average, increasing or decreasing in their relative abundance) to dietary fiber interventions across the studies. IMPORTANCE: Our study is an example of the power of synthesizing and reanalyzing 16S rRNA microbiome data from many intervention studies. Despite high inter-individual variation of the composition of the human gut microbiome, dietary fiber interventions cause a consistent response both in the degree of change and the particular taxa that respond to increased fiber.
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Fibras na Dieta , Microbioma Gastrointestinal , RNA Ribossômico 16S , Fibras na Dieta/administração & dosagem , Fibras na Dieta/metabolismo , Humanos , Microbioma Gastrointestinal/fisiologia , RNA Ribossômico 16S/genética , Fezes/microbiologia , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , FilogeniaRESUMO
INTRODUCTION: Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity. METHODS: Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration. RESULTS: Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease. DISCUSSION: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease.
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Biomarcadores , Doença Celíaca , Duodeno , Fezes , Proteínas de Ligação ao GTP , Imunoglobulina A , Complexo Antígeno L1 Leucocitário , Lipocalina-2 , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases , alfa 1-Antitripsina , Humanos , Doença Celíaca/diagnóstico , Doença Celíaca/sangue , Doença Celíaca/patologia , Feminino , Biomarcadores/sangue , Biomarcadores/análise , Masculino , Criança , alfa 1-Antitripsina/sangue , Complexo Antígeno L1 Leucocitário/análise , Complexo Antígeno L1 Leucocitário/sangue , Fezes/química , Lipocalina-2/sangue , Lipocalina-2/análise , Transglutaminases/imunologia , Transglutaminases/sangue , Estudos Prospectivos , Pré-Escolar , Imunoglobulina A/sangue , Proteínas de Ligação ao GTP/imunologia , Proteínas de Ligação ao GTP/sangue , Adolescente , Duodeno/patologia , Biópsia , Estudos de Casos e Controles , Lipocalinas/sangue , Proteínas de Fase Aguda/análise , Proteínas de Fase Aguda/metabolismo , Inflamação/diagnóstico , Inflamação/sangueRESUMO
Background: Although breastfeeding confers significant benefits to infants, women with diabetes in pregnancy experience unique nutrition and health challenges, which may influence infant feeding practice. This study aimed to determine the association between nutrition and exercise behaviors of women with diabetes in pregnancy and breastfeeding at birth and 6 months. Methods: A secondary data analysis of a longitudinal study on maternal pregestational diabetes mellitus (DM) and gestational diabetes (GDM) and infant development was conducted. Women self-reported engaging in nutrition behaviors, such as using meal plans, and exercise health behaviors. Primary outcomes were exclusive breastfeeding at birth and any breastfeeding at 6 months. Logistic regression models adjusted for significant maternal-infant covariates. Results: Of n = 48 women with diabetes in pregnancy, 94% had GDM and 6% had pregestational type 1 or type 2 DM. Forty percent of women exclusively breastfed at birth and 68% partially or exclusively breastfed at 6 months (of n = 34 with complete 6-month data). Women who cooked their own meals had two times greater adjusted odds of exclusive breastfeeding at birth (adjusted odds ratio [AOR] = 1.94, 95% confidence interval [CI] = 1.12-5.11), and women who exercised during pregnancy had seven times greater adjusted odds of any breastfeeding at 6 months (AOR = 7.2, 95% CI = 1.10-42.8). Conclusion: Nutrition and exercise behaviors were associated with exclusive breastfeeding at birth and any breastfeeding at 6 months. Health behaviors to effectively manage diabetes during pregnancy may inform efforts to improve breastfeeding initiation and duration, and future studies in a larger sample are needed.
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Aleitamento Materno , Diabetes Gestacional , Recém-Nascido , Gravidez , Criança , Lactente , Feminino , Humanos , Estudos Longitudinais , Comportamento AlimentarRESUMO
Background: The composition of the human gut microbiome varies tremendously among individuals, making the effects of dietary or treatment interventions difficult to detect and characterize. The consumption of fiber is important for gut health, yet the specific effects of increased fiber intake on the gut microbiome vary across studies. The variation in study outcomes might be due to inter-individual (or inter-population) variation or to the details of the interventions including the types of fiber, length of study, size of cohort, and molecular approaches. Thus, to identify consistent fiber-induced responses in the gut microbiome of healthy individuals, we re-analyzed 16S rRNA sequencing data from 21 dietary fiber interventions from 12 human studies, which included 2564 fecal samples from 538 subjects across all interventions. Results: Short-term increases in dietary fiber consumption resulted in highly consistent gut microbiome responses across studies. Increased fiber consumption explained an average of 1.5% of compositional variation (versus 82% of variation attributed to the individual), reduced alpha diversity, and resulted in phylogenetically conserved responses in relative abundances among bacterial taxa. Additionally, we identified bacterial clades, at approximately the genus level, that were highly consistent in their response (increasing or decreasing in their relative abundance) to dietary fiber interventions across the studies. Conclusions: Our study is an example of the power of synthesizing and reanalyzing microbiome data from many intervention studies. Despite high inter-individual variation of the composition of the human gut microbiome, dietary fiber interventions cause a consistent response both in the degree of change as well as the particular taxa that respond to increased fiber.
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Background: Circulating tissue transglutaminase IgA (TTG IgA) concentrations are sensitive and specific indicators of celiac disease, but discrepancies between serologic and histologic findings still occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as non-invasive means of evaluating disease activity. Methods: Participants with positive celiac serologies and controls with negative celiac serologies were enrolled at the time of upper endoscopy. Blood, stool and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin and alpha-1-antitrypsin and plasma lipcalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and TTG IgA concentration. Results: Lipocalin-2 was significantly elevated in the stool ( p =0.007) but not the plasma of participants with positive celiac serologies compared to controls. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100mg/dL was specific, but not sensitive for biopsy proven celiac disease. Conclusions: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role in the local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease and did not correlate with degree of histologic changes on biopsy. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared to controls, an elevation of greater than 100mg/dL was 90% specific for biopsy proven celiac disease.
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Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide curated and pre-processed genetic data and common metadata for comparison across the different studies.
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Microbioma Gastrointestinal , Microbiota , Humanos , Fibras na Dieta , Microbiota/genética , Reprodutibilidade dos Testes , RNA Ribossômico 16S/genéticaRESUMO
Whether microbes show habitat preferences is a fundamental question in microbial ecology. If different microbial lineages have distinct traits, those lineages may occur more frequently in habitats where their traits are advantageous. Sphingomonas is an ideal bacterial clade in which to investigate how habitat preference relates to traits because these bacteria inhabit diverse environments and hosts. Here we downloaded 440 publicly available Sphingomonas genomes, assigned them to habitats based on isolation source, and examined their phylogenetic relationships. We sought to address whether: (1) there is a relationship between Sphingomonas habitat and phylogeny, and (2) whether there is a phylogenetic correlation between key, genome-based traits and habitat preference. We hypothesized that Sphingomonas strains from similar habitats would cluster together in phylogenetic clades, and key traits that improve fitness in specific environments should correlate with habitat. Genome-based traits were categorized into the Y-A-S trait-based framework for high growth yield, resource acquisition, and stress tolerance. We selected 252 high quality genomes and constructed a phylogenetic tree with 12 well-defined clades based on an alignment of 404 core genes. Sphingomonas strains from the same habitat clustered together within the same clades, and strains within clades shared similar clusters of accessory genes. Additionally, key genome-based trait frequencies varied across habitats. We conclude that Sphingomonas gene content reflects habitat preference. This knowledge of how environment and host relate to phylogeny may also help with future functional predictions about Sphingomonas and facilitate applications in bioremediation.
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Importance: Associations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding. Objective: To assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months. Design, Setting, and Participants: This cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants. Exposures: Maternal symptomatic or asymptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language. Results: Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (ß = 0.31; 95% CI, -2.97 to 3.58), gross motor (ß = 0.82; 95% CI, -1.34 to 2.99), fine motor (ß = 0.36; 95% CI, -0.74 to 1.47), expressive language (ß = -1.00; 95% CI, -4.02 to 2.02), or receptive language (ß = 0.45; 95% CI, -2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores. Conclusions and Relevance: In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.
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COVID-19 , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Recém-Nascido , Criança , Feminino , Gravidez , Humanos , Lactente , Masculino , Pré-Escolar , Adulto , Estudos de Coortes , Estudos Prospectivos , COVID-19/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Transversais , Complicações Infecciosas na Gravidez/epidemiologia , SARS-CoV-2RESUMO
BACKGROUND: Studies have shown that infant temperament varies with maternal psychosocial factors, in utero illness, and environmental stressors. We predicted that the pandemic would shape infant temperament through maternal SARS-CoV-2 infection during pregnancy and/or maternal postnatal stress. To test this, we examined associations among infant temperament, maternal prenatal SARS-CoV-2 infection, maternal postnatal stress, and postnatal COVID-related life disruptions. METHODS: We tested 63 mother-infant dyads with prenatal maternal SARS-CoV-2 infections and a comparable group of 110 dyads without infections. To assess postnatal maternal stress, mothers completed the Perceived Stress Scale 4 months postpartum and an evaluation of COVID-related stress and life disruptions 6 months postpartum. Mothers reported on infant temperament when infants were 6-months-old using the Infant Behavior Questionnaire-Revised (IBQ-R) Very Short Form. RESULTS: Maternal SARS-CoV-2 infection during pregnancy was not associated with infant temperament or maternal postnatal stress. Mothers with higher self-reported postnatal stress rated their infants lower on the Positive Affectivity/Surgency and Orienting/Regulation IBQ-R subscales. Mothers who reported greater COVID-related life disruptions rated their infants higher on the Negative Emotionality IBQ-R subscale. CONCLUSIONS: Despite no effect of prenatal maternal SARS-CoV-2 infection, stress and life disruptions incurred by the COVID-19 pandemic were associated with infant temperament at 6-months. IMPACT: SARS-CoV-2 infection during pregnancy is not associated with postnatal ratings of COVID-related life disruptions, maternal stress, or infant temperament. Postnatal ratings of maternal stress during the COVID-19 pandemic are associated with normative variation in maternal report of infant temperament at 6 months of age. Higher postnatal ratings of maternal stress are associated with lower scores on infant Positive Affectivity/Surgency and Orienting/Regulation at 6 months of age. Higher postnatal ratings of COVID-related life disruptions are associated with higher scores on infant Negative Emotionality at 6 months of age.
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COVID-19 , Temperamento , Feminino , Humanos , Lactente , Temperamento/fisiologia , Pandemias , SARS-CoV-2 , Mães/psicologia , Comportamento do Lactente/fisiologia , Comportamento do Lactente/psicologiaRESUMO
INTRODUCTION: Depression is a public health concern, nearing 1.5 million cases and accounting for 9.7% of years lost due to disability. Several factors, including altitude, contribute to its development. Altitude has become a topic for recent research, but its association with depressive symptoms has not been fully clarified. Therefore, this study aimed to determine the association between altitude and depressive symptoms in the Peruvian population. METHODS: A retrospective, cross-sectional study of the 2019 Demographic and Family Health Survey (ENDES in Spanish) was conducted. The dependent variable, depressive symptoms, was measured using the Patient Health Questionnaire (PHQ-9) and the independent variable, altitude, was categorized into: <1500 meters above sea level (masl), 1500-2499 masl and ≥2500 masl. To evaluate the association between altitude and depressive symptoms, we used Poisson regression model, constructing crude and multiple models. RESULTS: Of those living at 1500 to 2499 masl and ≥2500 masl, 7.23% and 7.12% had depressive symptoms, respectively. After adjusting for confounding variables, high altitude was found to be associated with depressive symptoms (prevalence ratio adjusted (aPR): 1.38, 95% confidence interval: 1.04-1.84; aPR 1.41, 95% CI: 1.20-1.66). CONCLUSIONS: A statistically significant association was found between high altitude and depressive symptoms. This may be attributable to hypobaric hypoxia that occurs at high altitudes and its effects on brain function. This study's findings should be considered to identify the population at risk and expand the coverage of preventive and therapeutic measures in high-altitude areas of Peru with poor access to health services.
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Altitude , Depressão , Humanos , Peru/epidemiologia , Depressão/epidemiologia , Prevalência , Estudos Transversais , Estudos RetrospectivosRESUMO
The management of pulmonary arterial hypertension (PAH) has become more complex in recent years because of increased pharmacotherapy options and longer patient survival with increasing numbers of comorbidities. As such, more opportunities exist for drug-drug interactions between PAH-targeted medications and medications potentially used to treat comorbid conditions. In this review, we provide an overview of pharmaceutical metabolism by cytochrome P450 and discuss important drug-drug interactions for the 14 Food and Drug Administration-approved medications for PAH in the nitric oxide (NO), endothelin, and prostacyclin pathways. Among the targets in the NO pathway (sildenafil, tadalafil, and riociguat), important interactions with nitrates, protease inhibitors, and other phosphodiesterase inhibitors can cause profound hypotension. In the endothelin pathway, bosentan is associated with more drug interactions via CYP3A4 inhibition; macitentan and ambrisentan have fewer interactions of note. Although the parenteral therapies in the prostacyclin pathway bypass significant liver metabolism and avoid drug interactions, selexipag and oral treprostinil may exhibit interactions with CYP2C8 inhibitors such as gemfibrozil and clopidogrel, which can raise drug levels. Finally, we provide a framework for identifying potential drug-drug interactions and avoiding errors.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Humanos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Pulmonar Primária Familiar/complicações , Bosentana/uso terapêutico , Interações Medicamentosas , Anti-Hipertensivos/uso terapêuticoRESUMO
Volatile organic compounds (VOCs) from biological samples have unknown origins. VOCs may originate from the host or different organisms from within the host's microbial community. To disentangle the origin of microbial VOCs, volatile headspace analysis of bacterial mono- and co-cultures of Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, and stable isotope probing in biological samples of feces, saliva, sewage, and sputum were performed. Mono- and co-cultures were used to identify volatile production from individual bacterial species or in combination with stable isotope probing to identify the active metabolism of microbes from the biological samples. Vacuum-assisted sorbent extraction (VASE) was employed to extract the VOCs. VASE is an easy-to-use, commercialized, solvent-free headspace extraction method for semi-volatile and volatile compounds. The lack of solvents and the near-vacuum conditions used during extraction make developing a method relatively easy and fast when compared to other extraction options such as tert-butylation and solid phase microextraction. The workflow described here was used to identify specific volatile signatures from mono- and co-cultures. Furthermore, analysis of the stable isotope probing of human associated biological samples identified VOCs that were either commonly or uniquely produced. This paper presents the general workflow and experimental considerations of VASE in conjunction with stable isotope probing of live microbial cultures.
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Infecções Estafilocócicas , Compostos Orgânicos Voláteis , Bactérias , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Microextração em Fase Sólida/métodos , Solventes , Staphylococcus aureus , Compostos Orgânicos Voláteis/análiseRESUMO
Necrotizing enterocolitis (NEC) is a serious consequence of preterm birth and is often associated with gut bacterial microbiome alterations. However, little is known about the development of the gut virome in preterm infants, or its role in NEC. Here, using metagenomic sequencing, we characterized the DNA gut virome of 9 preterm infants who developed NEC and 14 gestational age-matched preterm infants who did not. Infants were sampled longitudinally before NEC onset over the first 11 weeks of life. We observed substantial interindividual variation in the gut virome between unrelated preterm infants, while intraindividual variation over time was significantly less. We identified viral and bacterial signatures in the gut that preceded NEC onset. Specifically, we observed a convergence towards reduced viral beta diversity over the 10 d before NEC onset, which was driven by specific viral signatures and accompanied by specific viral-bacterial interactions. Our results indicate that bacterial and viral perturbations precede the sudden onset of NEC. These findings suggest that early life virome signatures in preterm infants may be implicated in NEC.
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Enterocolite Necrosante , Doenças do Recém-Nascido , Nascimento Prematuro , Bactérias/genética , Enterocolite Necrosante/microbiologia , Fezes/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Viroma/genéticaRESUMO
Background and Aim: We sought to correlate two different measures of gut permeability [lactulose:mannitol (L:M) and lactulose:rhamnose (L:R)] to the severity of duodenal histopathology in children with and without elevated antibodies to tissue transglutaminase (tTG). A secondary objective was to correlate gut permeability with celiac disease (CD) serology and indices of inflammation and bacterial product translocation. Methods: We prospectively randomized children undergoing endoscopy with abnormal (n = 54) and normal (n = 10) concentrations of circulating antibodies to tTG, to either L:M or L:R. Biopsies underwent modified Marsh scoring to measure mucosal injury. Circulating anticore Escherichia coli lipopolysaccharide (LPS) IgG, α-1 acid glycoprotein, LPS-binding protein, and C-reactive protein concentrations were measured by enzyme immunoassays. Results: Of the 54 cases with positive celiac serology, 31 and 69% had modified Marsh 0/1 scores or ≥3a, respectively. Circulating tTG IgA correlated with the modified Marsh score (p = 0.03). L:R, but not L:M or percent L excreted, differed according to modified Marsh scores (p = 0.01). There was no significant association between any systemic marker of inflammation or gut injury, and modified Marsh scores. Concerningly, most participants had evidence of urinary M before the challenge sugar was administered. Conclusions: L:R, but not L:M, is associated with modified Marsh scores in children undergoing small bowel biopsy for suspected CD. Despite increased intestinal permeability, we see scant evidence of systemic exposure to gut microbes in these children. Gut permeability testing with L:R may predict which patients with abnormal celiac serology will have biopsy evidence for celiac disease and reduce the proportion of such patients undergoing endoscopy whose Marsh scores are ≤1. M should not be used as a monosaccharide for permeability testing in children.
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Resumen Objetivo: describir el perfil microbiológico de las superficies inanimadas en contacto con el paciente en un hospital nivel III de la seguridad social de Chiclayo, Perú. Material y métodos: Se realizó un estudio transversal, con los datos de los informes del Control microbiológico cualitativo de ambientes físicos de 5 servicios de un Hospital de Chiclayo nivel III del Perú. El método para la identificación de microorganismos fue el sistema automatizado VITEK MS. Se presentan análisis des criptivos como frecuencias y porcentajes. Resultados: Se reportaron un total de 177 aislamientos, de los cuales 97,74% (173) fueron positivos, de estos, el 50,87% (88) estuvo conformado por bacilos gram negativos, siendo el microorganismo más aislado Acinetobacter baumannii (17 muestras) seguido de Rhizobium radiobacter (16) y Sphingomonas paucimobilis 13. Conclusiones: El ambiente hospitalario se encuentra altamente contaminado, siendo la mayoría microorganismos patógenos. Estos resultados guardarían relación con el prolongado tiempo de vida de los microorganismos en las superficies inertes y el proceso de limpieza y desinfección del ambiente hospitalario, por lo que la evaluación de su eficacia y el posible desarrollo de nuevas y mejores técnicas de limpieza deben ser motivo de investigación.
Abstract Objective: to describe the microbiological profile of inanimate surfaces in contact with the patient in a social security level III hospital in Chiclayo, Peru. Material and methods: An observational, descriptive, transversal study was carried out with the data from the reports of the Microbiological Qualitative Control of Physical Environments of 5 services of a Chiclayo Hospital level III in Peru. The method for the identification of microorganisms was the automated system VITEK MS. Descriptive analyses such as frequencies and percentages are presented. Results: A total of 177 isolations were reported, from which 97.74% (173) were positive, of these, 50.87% (88) were composed by gram-negative bacilli, being the most isolated microorganism Acinetobacter baumannii (17 samples) followed by Rhizobium radiobacter (16) and Sphingomonas paucimobilis 13. Conclusions: The hospital environment is highly contaminated, being most of them pathogenic microorganisms. These results would be related to the long life of microorganisms on inert surfaces and the process of cleaning and disinfection of the hospital environment, so the evaluation of its effectiveness and the possible development of new and better cleaning techniques should be investigated.
RESUMO
OBJECTIVE/DESIGN: Cross-sectional study to examine the determinants of sleep health among postpartum women during the COVID-19 pandemic in New York City (NYC). SETTING/PARTICIPANTS: A subset of participants recruited as part of the COVID-19 Mother Baby Outcomes (COMBO) cohort at Columbia University (N = 62 non-Hispanic White, N = 17 African American, N = 107 Hispanic). MEASUREMENTS: Data on maternal sleep, COVID-19 infection during pregnancy, sociodemographic, behavioral, and psychological factors were collected via questionnaire at 4 months postpartum. Self-reported subjective sleep quality, latency, duration, efficiency, disturbances, and daytime dysfunction were examined as categorical variables (Pittsburgh Sleep Quality Index [PSQI]). Associations between sleep variables and COVID-19 status, time of the pandemic, sociodemographic, behavioral, and psychological factors were estimated via independent multivariable regressions. RESULTS: Mothers who delivered between May-December 2020, who delivered after the NYC COVID-19 peak, experienced worse sleep latency, disturbances and global sleep health compared to those who delivered March-April 2020, the peak of the pandemic. Maternal depression, stress and COVID-19-related post-traumatic stress were associated with all sleep domains except for sleep efficiency. Maternal perception of infant's sleep as a problem was associated with worse global PSQI score, subjective sleep quality, duration, and efficiency. Compared to non-Hispanic White, Hispanic mothers reported worse global PSQI scores, sleep latency, duration and efficiency, but less daytime dysfunction. CONCLUSIONS: These findings provide crucial information about sociodemographic, behavioral, and psychological factors contributing to sleep health in the postpartum period.
Assuntos
COVID-19 , Transtornos do Sono-Vigília/epidemiologia , Sono/fisiologia , COVID-19/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Lactente , Cidade de Nova Iorque/epidemiologia , Período Pós-Parto , Gravidez , Transtornos do Sono-Vigília/etnologia , Transtornos do Sono-Vigília/etiologia , Inquéritos e QuestionáriosRESUMO
Importance: Associations between in utero exposure to maternal SARS-CoV-2 infection and neurodevelopment are speculated, but currently unknown. Objective: To examine the associations between maternal SARS-CoV-2 infection during pregnancy, being born during the COVID-19 pandemic regardless of maternal SARS-CoV-2 status, and neurodevelopment at age 6 months. Design, Setting, and Participants: A cohort of infants exposed to maternal SARS-CoV-2 infection during pregnancy and unexposed controls was enrolled in the COVID-19 Mother Baby Outcomes Initiative at Columbia University Irving Medical Center in New York City. All women who delivered at Columbia University Irving Medical Center with a SARS-CoV-2 infection during pregnancy were approached. Women with unexposed infants were approached based on similar gestational age at birth, date of birth, sex, and mode of delivery. Neurodevelopment was assessed using the Ages & Stages Questionnaire, 3rd Edition (ASQ-3) at age 6 months. A historical cohort of infants born before the pandemic who had completed the 6-month ASQ-3 were included in secondary analyses. Exposures: Maternal SARS-CoV-2 infection during pregnancy and birth during the COVID-19 pandemic. Main Outcomes and Measures: Outcomes were scores on the 5 ASQ-3 subdomains, with the hypothesis that maternal SARS-CoV-2 infection during pregnancy would be associated with decrements in social and motor development at age 6 months. Results: Of 1706 women approached, 596 enrolled; 385 women were invited to a 6-month assessment, of whom 272 (70.6%) completed the ASQ-3. Data were available for 255 infants enrolled in the COVID-19 Mother Baby Outcomes Initiative (114 in utero exposed, 141 unexposed to SARS-CoV-2; median maternal age at delivery, 32.0 [IQR, 19.0-45.0] years). Data were also available from a historical cohort of 62 infants born before the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with significant differences on any ASQ-3 subdomain, regardless of infection timing or severity. However, compared with the historical cohort, infants born during the pandemic had significantly lower scores on gross motor (mean difference, -5.63; 95% CI, -8.75 to -2.51; F1,267 = 12.63; P<.005), fine motor (mean difference, -6.61; 95% CI, -10.00 to -3.21; F1,267 = 14.71; P < .005), and personal-social (mean difference, -3.71; 95% CI, -6.61 to -0.82; F1,267 = 6.37; P<.05) subdomains in fully adjusted models. Conclusions and Relevance: In this study, birth during the pandemic, but not in utero exposure to maternal SARS-CoV-2 infection, was associated with differences in neurodevelopment at age 6 months. These early findings support the need for long-term monitoring of children born during the COVID-19 pandemic.