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1.
Am J Perinatol ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38531390

RESUMO

OBJECTIVE: Non-Hispanic Black people (NHBP) have a three-fold higher rate of maternal mortality compared to other racial groups. Racial disparities in maternal morbidity are well-described; however, there are substantial differences in cultural, economic, and social determinants of health among racial groups. We thus sought to study the at-risk, non-Hispanic Black population as its own cohort to identify factors most associated with severe maternal morbidity (SMM). STUDY DESIGN: This is a population-based retrospective case-control study of all live births in the United States between 2017 and 2019 using birth records obtained from the National Center for Health Statistics. The primary outcome for this study was to determine demographic, social, medical, and obstetric factors associated with maternal morbidity among NHBP who did and did not experience an SMM event. Multivariable logistic regression was used to estimate the adjusted odds ratio between each individual factor and the outcome of SMM among NHBP. RESULTS: Of the 1,624,744 NHBP who delivered between 2017 and 2019, 1.1% experienced an SMM event defined as a composite of blood product transfusion, eclamptic seizure, intensive care unit admission, unplanned hysterectomy, and uterine rupture. The rates of these individual SMM events per 10,000 deliveries were 50, 40, 20, 5, and 4 among NHBP, respectively. Among NHBP, factors associated in multivariable regression analysis with SMM in order of strength of association included cesarean delivery, earlier gestational age at delivery, preeclampsia, induction of labor, chronic hypertension, prior preterm birth, lower educational attainment, multifetal gestation, advanced maternal age, pregestational diabetes, and cigarette smoking. The population attributable fraction for cesarean delivery, preterm birth, and pregnancy-induced hypertensive disease for the outcome of SMM were 0.46, 0.23, and 0.07, respectively. CONCLUSION: The three factors most associated with SMM among NHBP are potentially avoidable or modifiable by aggressive screening, prevention, and treatment of preeclampsia and preterm birth as well as reducing cesarean rates in this population. KEY POINTS: · The rate of SMM in NHBP may be modifiable.. · NHBP have a three-fold higher rate of maternal mortality.. · Preeclampsia, preterm birth, and cesarean sections are most associated with maternal morbidity..

2.
Nat Immunol ; 25(2): 316-329, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38182669

RESUMO

Pneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain unknown. We vaccinated 39 older adults (>60 years) with PPSV23 or PCV13 and observed comparable antibody responses (day 28) and plasmablast transcriptional responses (day 10); however, the baseline predictors were distinct. Analyses of baseline flow cytometry and bulk and single-cell RNA-sequencing data revealed a baseline phenotype specifically associated with weaker PCV13 responses, which was characterized by increased expression of cytotoxicity-associated genes, increased frequencies of CD16+ natural killer cells and interleukin-17-producing helper T cells and a decreased frequency of type 1 helper T cells. Men displayed this phenotype more robustly and mounted weaker PCV13 responses than women. Baseline expression levels of a distinct gene set predicted PPSV23 responses. This pneumococcal precision vaccinology study in older adults uncovered distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.


Assuntos
Anticorpos Antibacterianos , Streptococcus pneumoniae , Masculino , Humanos , Feminino , Idoso , Vacinas Conjugadas , Método Duplo-Cego , Vacinação , Vacinas Pneumocócicas , Polissacarídeos
3.
Prehosp Emerg Care ; 28(2): 390-397, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36862061

RESUMO

INTRODUCTION: The transition of Army Combat Medic Specialists (Military Occupational Specialty Code: 68W) from military to civilian emergency medical services (EMS) is challenging, and the pathway is not clearly defined. Our objective was to evaluate the current military requirements for 68W and how they compare to the 2019 EMS National Scope of Practice Model (SoPM) for the civilian emergency medical technician (EMT) and advanced emergency medical technician (AEMT). METHODS: This was a cross-sectional evaluation of the 68W skill floor as defined by the Soldier's Manual and Trainer's Guide Healthcare Specialist and Medical Education and Demonstration of Individual Competence in comparison to the 2019 SoPM, which categorizes EMS tasks into seven skill categories. Military training documents were reviewed and extracted for specific information on military scope of practice and task-specific training requirements. Descriptive statistics were calculated. RESULTS: Army 68Ws were noted to perform all (59/59) tasks that coincide with the EMT SoPM. Further, Army 68W practiced above scope in the following skill categories: airway/ventilation (3 tasks); medication administration route (7 tasks); medical director approved medication (6 tasks); intravenous initiation maintenance fluids (4 tasks); and miscellaneous (1 task). Army 68W perform 96% (74/77) of tasks aligned with the AEMT SoPM, excluding tracheobronchial suctioning of an intubated patient, end-tidal CO2 monitoring or waveform capnography, and inhaled nitrous oxide monitoring. Additionally, the 68W scope included six tasks that were above the SoPM for AEMT; airway/ventilation (2 tasks); medication administration route (2 tasks); and medical director approved medication (2 tasks). CONCLUSIONS: The scope of practice of U.S. Army 68W Combat Medics aligns well with the civilian 2019 Scope of Practice Model for EMTs and AEMTs. Based on the comparative scope of practice analysis, transitioning from Army 68W Combat Medic to civilian AEMT would require minimal additional training. This represents a promising potential workforce to assist with EMS workforce challenges. Although aligning the scope of practice is a promising first step, future research is needed to assess the relationship of Army 68Ws training with state licensure and certification equivalency to facilitate this transition.


Assuntos
Serviços Médicos de Emergência , Auxiliares de Emergência , Militares , Humanos , Médicos de Combate , Estudos Transversais , Âmbito da Prática , Certificação
4.
Sci Total Environ ; 904: 166937, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37696399

RESUMO

In the southern San Joaquin Valley (SJV) of California, an agriculturally productive region that relies on groundwater for irrigation and domestic water supply, the infiltration of produced water from oil reservoirs is known to impact groundwater due to percolation from unlined disposal ponds. However, previously documented impacts almost exclusively focus on salinity, while contaminant loadings commonly associated with produced water (e.g., radionuclides) are poorly constrained. For example, the infiltration of bicarbonate-rich produced waters can react with sediment-bound uranium (U), leading to U mobilization and subsequent transport to nearby groundwater. Specifically, produced water infiltration poses a particular concern for SJV groundwater, as valley-fill sediments are well documented to be enriched in geogenic, reduced U. Here, we analyzed monitoring well data from two SJV produced water pond facilities to characterize U mobilization and subsequent groundwater contamination. Groundwater wells installed within 2 km of the facilities contained produced water and elevated levels of uranium. There are >400 produced water disposal pond facilities in the southern SJV. If our observations occur at even a fraction of these facilities, there is the potential for widespread U contamination in the groundwaters of one of the most productive agricultural regions in the world.

5.
JAMA Netw Open ; 6(8): e2328335, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37566418

RESUMO

Importance: Despite the increased perinatal risks associated with pregnancies conceived with infertility treatment, there are no recommendations for timing of delivery among this at-risk population. Objective: To identify the gestational age at which the ongoing risks of stillbirth are optimally balanced with the risks of neonatal comorbidities and infant deaths in term singleton pregnancies conceived with infertility treatment. Design, Setting, and Participants: This cohort study used birth and death data from January 1, 2014, to December 31, 2018, in the US obtained from the National Center for Health Statistics. Singleton pregnancies conceived with infertility treatment delivered at term (37-42 weeks' gestation) were eligible for inclusion. The exclusion criteria were deliveries at less than 37 weeks' or at least 43 weeks' gestation and pregnancies with unknown history of infertility treatment, congenital anomalies, pregestational diabetes, pregestational hypertension, gestational hypertension, and preeclampsia. Data were analyzed from July 22, 2022, to June 24, 2023. Exposure: Gestational age at delivery between 37 and 42 weeks. Main Outcomes and Measures: The primary outcome was optimal timing of delivery. To ascertain this timing, the risk of delivery (rate of neonatal morbidity and infant death) at a given gestational week was compared with the risk of delivery in the subsequent week of gestation for an additional week (rate of stillbirth during the given week per 10 000 ongoing pregnancies plus rate of neonatal morbidity and infant death in the subsequent week of gestation per 10 000 deliveries). The rates of stillbirth, neonatal morbidity, and infant death (within 1 year of life) were compared at each week. Neonatal morbidity included an Apgar score of 3 or lower at 5 minutes, requirement of ventilation for 6 hours or more, neonatal intensive care unit admission, and seizures. Results: Of the 178 448 singleton term pregnancies conceived with infertility treatment (maternal mean [SD] age, 34.2 [5.2] years; mean [SD] gestational age, 39.2 [1.2] weeks; 130 786 [73.5%] were non-Hispanic White patients). The risk of delivery in the subsequent week of gestation was lower than the risk of delivery at both 37 weeks (628 [95% CI, 601-656] vs 1005 [95% CI, 961-1050] per 10 000 live births) and 38 weeks (483 [95% CI, 467-500 vs 625 [95% CI, 598-652] per 10 000 live births). The risks of delivery in subsequent week of gestation significantly exceeded the risk of delivery at 39 weeks (599 [95% CI, 576-622] vs 479 [95% CI, 463-495] per 10 000 live births) and were not significant at 40 weeks (639 [95% CI, 605-675] vs 594 [95% CI, 572-617] per 10 000 live births) and 41 weeks (701 [95% CI, 628-781] vs 633 [95% CI, 599-669] per 10 000 live births). Conclusions and Relevance: Results of this study suggest that, in pregnancies conceived with infertility treatment, delivery at 39 weeks provided the lowest perinatal risk when comparing risk of delivery at this week of gestation vs the subsequent week of gestation.


Assuntos
Infertilidade , Natimorto , Lactente , Recém-Nascido , Gravidez , Feminino , Humanos , Adulto , Natimorto/epidemiologia , Idade Gestacional , Estudos de Coortes , Morte do Lactente
6.
BMC Med ; 21(1): 258, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37455310

RESUMO

BACKGROUND: Preterm birth (PTB), defined as delivery before 37 gestational weeks, imposes significant public health burdens. A recent maternal genome-wide association study of spontaneous PTB identified a noncoding locus near the angiotensin II receptor type 2 (AGTR2) gene. Genotype-Tissue Expression data revealed that alleles associated with decreased AGTR2 expression in the uterus were linked to an increased risk of PTB and shortened gestational duration. We hypothesized that a causative variant in this locus modifies AGTR2 expression by altering transcription factor (TF) binding. METHODS: To investigate this hypothesis, we performed bioinformatics analyses and functional characterizations at the implicated locus. Potential causal single nucleotide polymorphisms (SNPs) were prioritized, and allele-dependent binding of TFs was predicted. Reporter assays were employed to assess the enhancer activity of the top PTB-associated non-coding variant, rs7889204, and its impact on TF binding. RESULTS: Our analyses revealed that rs7889204, a top PTB-associated non-coding genetic variant is one of the strongest eQTLs for the AGTR2 gene in uterine tissue samples. We observed differential binding of CEBPB (CCAAT enhancer binding protein beta) and HOXA10 (homeobox A10) to the alleles of rs7889204. Reporter assays demonstrated decreased enhancer activity for the rs7889204 risk "C" allele. CONCLUSION: Collectively, these results demonstrate that decreased AGTR2 expression caused by reduced transcription factor binding increases the risk for PTB and suggest that enhancing AGTR2 activity may be a preventative measure in reducing PTB risk.


Assuntos
Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Nascimento Prematuro/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Fatores de Transcrição/genética
7.
ACS Omega ; 8(22): 19443-19454, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37305312

RESUMO

The U.S. Environmental Protection Agency estimates that there are over 3.2 million abandoned wells in the United States. Studies conducted on gas emissions from abandoned wells have been limited to methane, a powerful greenhouse gas, due to concerns regarding climate change. However, volatile organic compounds (VOCs), including benzene, a known human carcinogen, are known to be associated with upstream oil and gas development and hence could also be released when methane is emitted to the atmosphere. In this investigation, we analyze gas from 48 abandoned wells in western Pennsylvania for fixed gases, light hydrocarbons, and VOCs and estimate associated emission rates. We demonstrate that (1) gas from abandoned wells contains VOCs, including benzene; (2) VOCs are emitted from abandoned wells, the magnitude of which depends on the flow rate and concentration of VOCs in the gas stream; and (3) nearly one-quarter of abandoned wells are located within 100 m of buildings, including residences, in Pennsylvania. Together, these observations indicate that further investigation is necessary to determine whether emissions from abandoned wells pose an inhalation risk to people living, working, or congregating near abandoned wells.

8.
Environ Sci Technol ; 57(19): 7559-7567, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37146013

RESUMO

Oil and gas development generates large amounts of wastewater (i.e., produced water), which in California has been partially disposed of in unlined percolation/evaporation ponds since the mid-20th century. Although produced water is known to contain multiple environmental contaminants (e.g., radium and trace metals), prior to 2015, detailed chemical characterizations of pondwaters were the exception rather than the norm. Using a state-run database, we synthesized samples (n = 1688) collected from produced water ponds within the southern San Joaquin Valley of California, one of the most productive agricultural regions in the world, to examine regional trends in pondwater arsenic and selenium concentrations. We filled crucial knowledge gaps resulting from historical pondwater monitoring by constructing random forest regression models using commonly measured analytes (boron, chloride, and total dissolved solids) and geospatial data (e.g., soil physiochemical data) to predict arsenic and selenium concentrations in historical samples. Our analysis suggests that both arsenic and selenium levels are elevated in pondwaters and thus this disposal practice may have contributed substantial amounts of arsenic and selenium to aquifers having beneficial uses. We further use our models to identify areas where additional monitoring infrastructure would better constrain the extent of legacy contamination and potential threats to groundwater quality.


Assuntos
Arsênio , Água Subterrânea , Selênio , Poluentes Químicos da Água , Selênio/análise , Poluentes Químicos da Água/análise , Água , Água Subterrânea/análise , Monitoramento Ambiental
9.
medRxiv ; 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37131707

RESUMO

Pneumococcal infections cause serious illness and death among older adults. A capsular polysaccharide vaccine PPSV23 (Pneumovax®) and a conjugated polysaccharide vaccine PCV13 (Prevnar®) are used to prevent these infections, yet underlying responses, and baseline predictors remain unknown. We recruited and vaccinated 39 older adults (>60 years) with PPSV23 or PCV13. Both vaccines induced strong antibody responses at day 28 and similar plasmablast transcriptional signatures at day 10, however, their baseline predictors were distinct. Analyses of baseline flow cytometry and RNA-seq data (bulk and single cell) revealed a novel baseline phenotype that is specifically associated with weaker PCV13 responses, characterized by i) increased expression of cytotoxicity-associated genes and increased CD16+ NK frequency; ii) increased Th17 and decreased Th1 cell frequency. Men were more likely to display this cytotoxic phenotype and mounted weaker responses to PCV13 than women. Baseline expression levels of a distinct gene set was predictive of PPSV23 responses. This first precision vaccinology study for pneumococcal vaccine responses of older adults uncovered novel and distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.

10.
Geohealth ; 7(3): e2022GH000690, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36968155

RESUMO

People living near oil and gas development are exposed to multiple environmental stressors that pose health risks. Some studies suggest these risks are higher for racially and socioeconomically marginalized people, which may be partly attributable to disparities in exposures. We examined whether racially and socioeconomically marginalized people in California are disproportionately exposed to oil and gas wells and associated hazards. We longitudinally assessed exposure to wells during three time periods (2005-2009, 2010-2014, and 2015-2019) using sociodemographic data at the census block group-level. For each block group and time period, we assessed exposure to new, active, retired, and plugged wells, and cumulative production volume. We calculated risk ratios to determine whether marginalized people disproportionately resided near wells (within 1 km). Averaged across the three time periods, we estimated that 1.1 million Californians (3.0%) lived within 1 km of active wells. Nearly 9 million Californians (22.9%) lived within 1 km of plugged wells. The proportion of Black residents near active wells was 42%-49% higher than the proportion of Black residents across California, and the proportion of Hispanic residents near active wells was 4%-13% higher than their statewide proportion. Disparities were greatest in areas with the highest oil and gas production, where the proportion of Black residents was 105%-139% higher than statewide. Socioeconomically marginalized residents also had disproportionately high exposure to wells. Though oil and gas production has declined in California, marginalized communities persistently had disproportionately high exposure to wells, potentially contributing to health disparities.

11.
ACS ES T Water ; 3(3): 650-658, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36970186

RESUMO

Toxic levels of trace metals from human activities accumulate in natural environments, yet these metal mixtures are rarely characterized or quantified. Metal mixtures accumulate in historically industrial urban areas and change as economies shift. Previous research has often focused on the sources and fate of a specific element, which limits our understanding of metal contaminant interactions in our environment. Here, we reconstruct the history of metal contamination in a small pond downstream of an interstate highway and downwind of fossil fuel and metallurgical industries that have been active since the middle of the nineteenth century. Metal contamination histories were reconstructed from the sediment record using metal ratio mixing analysis to attribute the relative contributions of contamination sources. Cadmium, copper, and zinc concentrations in sediments accumulated since the construction of major road arteries in the 1930s and 40s are, respectively, 3.9, 2.4, and 6.6 times more concentrated than those during industry-dominated time periods. Shifts in elemental ratios suggest these changes in metal concentrations coincide with increased contributions from road and parking lot traffic, and to a lesser extent, from airborne sources. The metal mixture analysis demonstrates that in near-road environments, contributions from modern surface water pathways can obscure historical atmospheric industrial inputs.

12.
Am J Perinatol ; 40(16): 1789-1797, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-34839472

RESUMO

OBJECTIVE: In 2014, the leading obstetric societies published an executive summary of a joint workshop to establish obstetric interventions to be considered for periviable births. Antenatal corticosteroid administration between 220/7 and 226/7 weeks was not recommended given existing evidence. We sought to evaluate whether antenatal steroid exposure was associated with improved survival among resuscitated newborns delivered between 22 and 23 weeks of gestation. STUDY DESIGN: We conducted a population-based cohort study of all resuscitated livebirths delivered between 220/7 and 236/7 weeks of gestation in the United States during 2009 to 2014 utilizing National Center for Health Statistics data. The primary outcome was rate of survival to 1 year of life (YOL) between infant cohorts based on antenatal steroid exposure. Multivariable logistic regression estimated the association of antenatal steroid exposure on survival outcomes. RESULTS: In the United States between 2009 and 2014, there were 2,635 and 7,992 infants who received postnatal resuscitation after delivery between 220/7 to 226/7 and 230/7 to 236/7 weeks of gestation, respectively. Few infants born at 22 (15.9%) and 23 (26.0%) weeks of gestation received antenatal corticosteroids (ANCS). Among resuscitated neonates, survival to 1 YOL was 45.2 versus 27.8% (adjusted relative risk [aRR]: 1.6, 95% confidence interval [CI]: 1.2-2.1) and 57.9 versus 47.7% (aRR: 1.3, 95% CI: 1.1-1.5) for infants exposed to ANCS compared with those not exposed at 22 and 23 weeks of gestation, respectively. When stratified by 100 g birth weight category, ANCS were associated with survival among neonates weighing 500 to 599 g (aRR: 1.9, 95% CI: 1.3-2.9) and 600 to 699 g (aRR: 1.7, 95% CI: 1.1-2.6) at 22 weeks. CONCLUSION: Exposure to ANCS was associated with higher survival rates to 1 YOL among resuscitated infants born at 22 and 23 weeks. National guidelines recommending against ANCS utilization at 22 weeks should be re-evaluated given emerging evidence of benefit. KEY POINTS: · Exposure to antenatal steroids was associated with higher survival rates at 22 and 23 weeks of gestation.. · Women exposed to antenatal steroids were more likely to have an adverse outcome.. · The association between steroids and survival was observed among infants with birth weights > 500 g..


Assuntos
Corticosteroides , Gravidez Múltipla , Recém-Nascido , Lactente , Humanos , Gravidez , Feminino , Estudos de Coortes , Idade Gestacional , Corticosteroides/uso terapêutico , Esteroides , Peso ao Nascer
13.
Environ Sci Pollut Res Int ; 30(7): 18631-18642, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36215008

RESUMO

Accidental releases (i.e., spills) of produced water can occur at any point during oil and gas development operations, potentially resulting in chronic and/or catastrophic loadings of produced water to nearby ecosystems and exposures of human populations to toxic constituents including trace metals (e.g., arsenic), organic compounds (e.g., benzene), and/or radionuclides (e.g., radium). Despite California being one of the largest oil and gas producing states in the USA, no comprehensive reviews of produced water spills in the peer-reviewed literature have been published. To address this knowledge gap, produced water spill incident data contained within the California HazMat database were synthesized to elucidate trends in produced water spills in California. During the period of 2006-2020, a total of 1029 incidents involving produced water spills were reported. Despite the potential threat to environmental and human receptors, there are significant knowledge gaps concerning these incidents. Specifically, only ~ 6% of spill incidents contained geographic coordinates, greatly hindering assessments of the impacts of these events to public health and the environment. Moreover, updated spill volumes are not rapidly retrievable from the HazMat database, and during the years 2018-2020 volumes of produced water spilled were underreported in initial reports anywhere from 35-2750%. Further, it is unclear if groundwater monitoring is performed following spill events. This study highlights significant shortcomings in produced water spill reporting in California and recommends improvements to aid future investigations that assess the environmental and public health impacts of spill incidents.


Assuntos
Água Subterrânea , Poluição por Petróleo , Humanos , Ecossistema , Água , Acidentes , Benzeno , Poluição por Petróleo/análise
14.
Am J Perinatol ; 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35623626

RESUMO

OBJECTIVE: The aim of this study was to quantify the influence of maternal sociodemographic, medical, and pregnancy characteristics on not receiving maternal and neonatal interventions with deliveries occurring at 22 to 23 weeks of gestation. STUDY DESIGN: This was a case-control study of U.S. live births at 220/6 to 236/7 weeks of gestation using vital statistics birth records from 2012 to 2016. We analyzed births that received no interventions for periviable delivery. Births were defined as having no interventions if they did not receive maternal (cesarean delivery, maternal hospital transfer, or antenatal corticosteroid administration) or neonatal interventions (neonatal intensive care unit admission, surfactant administration, antibiotic administration, or assisted ventilation). Logistic regression estimated the influence of maternal and pregnancy factors on the receipt of no interventions when delivery occurred at 22 to 23 weeks. RESULTS: Of 19,844,580 U.S. live births in 2012-2016, 24,379 (0.12%) occurred at 22 to 23 weeks; 54.3% of 22-week deliveries and 15.7% of 23-week deliveries received no interventions. Non-Hispanic Black maternal race was associated with no maternal interventions at 22 and 23 weeks. Private insurance, singleton pregnancy, and small for gestational age were associated with receiving no neonatal interventions at 22 and 23 weeks of gestation. CONCLUSIONS: Withholding or refusing maternal and neonatal interventions occurs frequently at the threshold of viability. Our data highlight various sociodemographic, pregnancy, and medical factors associated with decisions to not offer or receive maternal or neonatal interventions when birth occurs at the threshold of viability. The data elucidate observed practices and may assist in the development of further research. KEY POINTS: · Non-Hispanic Black race was associated with receiving no maternal interventions.. · Indicators of high socioeconomic status were associated with no neonatal inventions.. · Patient-level factors influence the receipt of no interventions for periviable birth..

15.
Sci Adv ; 8(3): eabg6711, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35044822

RESUMO

Tumors display widespread transcriptome alterations, but the full repertoire of isoform-level alternative splicing in cancer is unknown. We developed a long-read (LR) RNA sequencing and analytical platform that identifies and annotates full-length isoforms and infers tumor-specific splicing events. Application of this platform to breast cancer samples identifies thousands of previously unannotated isoforms; ~30% affect protein coding exons and are predicted to alter protein localization and function. We performed extensive cross-validation with -omics datasets to support transcription and translation of novel isoforms. We identified 3059 breast tumor­specific splicing events, including 35 that are significantly associated with patient survival. Of these, 21 are absent from GENCODE and 10 are enriched in specific breast cancer subtypes. Together, our results demonstrate the complexity, cancer subtype specificity, and clinical relevance of previously unidentified isoforms and splicing events in breast cancer that are only annotatable by LR-seq and provide a rich resource of immuno-oncology therapeutic targets.


Assuntos
Neoplasias da Mama , Processamento Alternativo , Neoplasias da Mama/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Análise de Sequência de RNA/métodos , Transcriptoma
16.
Am J Perinatol ; 39(1): 84-91, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32736406

RESUMO

OBJECTIVE: We sought to quantify the distribution of stillbirths by gestational age (GA) in a contemporary cohort and to determine identifiable risk factors associated with stillbirth prior to 32 weeks of gestation. STUDY DESIGN: Population-based case-control study of all stillbirths in the United States during the year 2014, utilizing vital statistics data, obtained from the National Center for Health Statistics. Distribution of stillbirths were stratified by 20 to 44 weeks of GA, in women diagnosed with stillbirth in the antepartum period. Pregnancy characteristics were compared between those diagnosed with stillbirth <32 versus ≥32 weeks of gestation. Multivariate logistic regression estimated the relative influence of various factors on the outcome of stillbirth prior to 32 weeks of gestation. RESULTS: There were 15,998 nonlaboring women diagnosed with stillbirth during 2014 in the United States between 20 and 44 weeks. Of them, 60.1% (n = 9,618) occurred before antenatal fetal surveillance (ANFS) is typically initiated (<32 weeks) and 39.9% (n = 6,380) were diagnosed at ≥32 weeks. Women with stillbirth prior to 32 weeks were more likely to be of non-Hispanic Black race (29.0 vs. 23.9%, p < 0.001), nulliparous (53.8 vs. 50.6%, p = 0.001), have chronic hypertension (CHTN; 6.0 vs. 4.3%, p < 0.001), and fetal growth restriction as evidenced by small for GA (SGA < 10th%) birth weight (44.8 vs. 42.1%, p < 0.001) as opposed to women with stillbirth after 32 weeks. After adjustment, SGA birth weight (adjusted odds ratio [aOR] = 1.2, 95% confidence interval [CI]: 1.1-1.3), Black race (aOR = 1.2, 95% CI: 1.1-1.3), and CHTN (aOR = 1.3, 95% CI: 1.1-1.5) were associated with stillbirth prior to 32 weeks of gestation as opposed to stillbirth after 32 weeks. CONCLUSION: More than 6 out of 10 stillbirths in this study occurred <32 weeks of gestation, before ANFS is typically initiated under American College of Obstetricians and Gynecologists recommendations. Among identifiable risk factors, CHTN, Black race, and fetal growth restriction were associated with higher risk of stillbirth before 32 weeks of gestation. Earlier ANFS may be warranted at in certain "at risk" women. KEY POINTS: · Six out of 10 stillbirths occur before 32 weeks of gestation.. · We evaluated factors associated with stillbirth <32 weeks.. · Hypertension and fetal growth restriction were associated with early stillbirth..


Assuntos
Retardo do Crescimento Fetal , Idade Gestacional , Hipertensão , Gravidez em Diabéticas , Natimorto , Negro ou Afro-Americano , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Hipertensão Induzida pela Gravidez , Recém-Nascido Pequeno para a Idade Gestacional , Modelos Logísticos , Gravidez , Fatores de Risco , Natimorto/epidemiologia , Natimorto/etnologia , Estados Unidos/epidemiologia
17.
J Matern Fetal Neonatal Med ; 35(25): 5957-5963, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33771076

RESUMO

OBJECTIVE: To quantify the frequency of serious maternal complications associated with cerclage use during pregnancy. STUDY DESIGN: We performed a retrospective population-based cohort study of all live births in Ohio from 2006 to 2015. Maternal sociodemographic, medical, and obstetric characteristics were compared for births in which cerclage was utilized during the pregnancy versus those without cerclage. The primary outcome for the study was a composite of adverse outcome including maternal intensive care unit (ICU) admission, blood product transfusion, uterine rupture and unplanned hysterectomy in all births. Secondary outcomes included each of the individual adverse outcomes as well as maternal hospital transfer to a tertiary facility, unplanned operation after delivery and chorioamnionitis. Each outcome was also analyzed separately in singleton and twin births. Generalized linear modeling was used to estimate the relative risk of adverse maternal outcomes associated with cerclage placement after adjustment for coexisting risk factors. RESULTS: Of the 1,428,655 singleton and twin live births in Ohio from 2006 to 2015, 4595 [0.3%] were recorded on the birth certificate as having cerclage during pregnancy. Of those, 11.7% experienced a serious adverse maternal outcome, compared to 3.7% without cerclage, adjRR 2.7 [95% CI 2.5, 3.0]. The rate of the composite maternal adverse outcome was significantly increased for pregnancies with cerclage versus those without overall, and in singleton and twin pregnancies when measured individually [all p ≤ .001]. Even after adjustment for coexisting risk factors, cerclage remained significantly associated with composite adverse outcome in each of these groups. CONCLUSIONS: Over 1 in 10 women with cerclage experience an adverse maternal outcome. Even after adjusting for gestational age at delivery and other risk factors, maternal risk for serious adverse event remains over twofold increased for pregnancies with cerclage. This information may be helpful in counseling women regarding potential maternal risk when considering neonatal benefit of cerclage in pregnancies at high risk of preterm birth.


Assuntos
Cerclagem Cervical , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Cerclagem Cervical/efeitos adversos , Nascimento Prematuro/epidemiologia , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Estudos de Coortes , Gravidez de Gêmeos
18.
JACC Adv ; 1(4): 100125, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38939712

RESUMO

Background: Maternal risk factors for fetal congenital heart disease (CHD) may also be associated with delivery complications in the mother. Objectives: This study aimed to determine the prevalence of and risk factors for severe maternal morbidity (SMM) and maternal hospital transfer in pregnancies complicated by fetal CHD. Methods: A population-based retrospective cohort study utilizing linked Ohio birth certificates and birth defect data for all live births from 2011 to 2015 was performed. The primary outcome was composite SMM. Secondary outcome was maternal hospital transfer prior to delivery. Pregnancies with isolated fetal CHD were compared to pregnancies with no fetal anomalies and isolated fetal cleft lip/palate (CLP). Results: A total of 682,929 mothers with live births were included. Of these, 5,844 (0.85%) mothers had fetal CHD, and 963 (0.14%) had fetal CLP. SMM in pregnancies with fetal CHD was higher than that in those with no anomalies (3.6% vs 1.9%, P < 0.001) or CLP (3.6% vs 1.9%, P = 0.006). After adjusting for known risk factors, fetal CHD remained independently associated with SMM when compared to no fetal anomalies (adjusted relative risk [adjRR]: 1.81, 95% CI: 1.58-2.08) and CLP (adjRR: 1.81, 95% CI: 1.12-2.92). Maternal hospital transfer occurred more frequently in fetal CHD cases vs for those without fetal anomalies with an increased adjusted risk (adjRR: 3.65, 95% CI: 3.14-4.25). Conclusions: Pregnancies with isolated fetal CHD have increased risk of SMM and maternal hospital transfer after adjusting for known risk factors. This may inform delivery planning for mothers with fetal CHD. Understanding the biological mechanisms may provide insight into other adverse perinatal outcomes in this population.

19.
Environ Sci Technol ; 55(21): 14782-14794, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34651501

RESUMO

The San Joaquin Valley (SJV) in California is one of the most agriculturally productive regions in the world relying in part on groundwater for irrigation and for domestic or municipal water supply for nearly 4 million residents. One area of growing concern in the SJV is potential impact to groundwater resources from ongoing and historical disposal of oilfield-produced water into unlined produced water ponds (PWPs). In this investigation, we utilized available information on composition of produced water disposed into unlined PWPs and levels of total dissolved solids in underlying groundwater to demonstrate that this disposal practice, both past and present, poses risks to groundwater resources, especially in the Tulare Basin in the southern SJV. Groundwater monitoring at unlined PWP facilities is relatively sparse, but where monitoring has occurred, impact to aquifers used for public and agricultural water supply has been observed and has proven to be too expensive to actively remediate. Results of this investigation should inform policy discussions in California and other locations where disposal of produced water into unlined impoundments occurs, especially at locations that overlie groundwater resources.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , California , Monitoramento Ambiental , Lagoas , Água , Poluentes Químicos da Água/análise , Abastecimento de Água
20.
Sci Total Environ ; 780: 146572, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33774307

RESUMO

Soils are the largest dynamic stock of carbon (C) on Earth, and microbial respiration of soil organic C accounts for over 25% of global carbon dioxide (CO2) emissions. Zones of oxygen depletion in upland soils (anaerobic microsites) are increasingly recognized as an important control on soil microbial respiration rates, but the factors governing the volume and distribution of anaerobic microsites are relatively unknown. We measured the dissolved oxygen (DO) content of porewater from incubated soil cores of varying moisture contents (<80% and >80% water saturation) and degrees of disturbance (undisturbed, conventionally tilled, and physically disturbed). Porewater was extracted sequentially from pores constrained by three effective pore diameters, ≥3.0 µm, 3.0-1.0 µm, and 1.0-0.6 µm, from cores incubated for 7, 14, or 28 days, using a modified Tempe cell extraction system. We observed a parabolic pattern in mean dissolved oxygen (DO) concentrations across pore sizes, independent of soil moisture and degree of disturbance. Specifically, DO values within the largest and smallest pore domains were relatively depleted (155 ± 10 µM and 160 ± 11 µM, respectively), while DO values within medium pores were closer to saturation (214 ± 8 µM). The observed DO pattern provides insight into the balance of microbial oxygen demand versus oxygen supply across pore domains within upland soils. Additionally, we observed iron and manganese reduction in all soils except samples subjected to disturbance and incubated at <80% water saturation, suggesting that disturbance enhances aeration and diminishes anaerobic metabolisms within upland soils. Our findings highlight the influence of soil moisture and management on soil redox and CO2 efflux rates.


Assuntos
Dióxido de Carbono , Solo , Anaerobiose , Dióxido de Carbono/análise , Oxigênio , Microbiologia do Solo , Água
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