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1.
Clin Pediatr (Phila) ; 63(4): 494-505, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37309802

RESUMO

This study aims to compare the developmental-behavioral profiles of 2-year-olds of mothers who experienced postpartum and/or current depression with profiles of toddlers of mothers without depression at either time using population-based Rhode Island data. Weighted data from Rhode Island Department of Health's Pregnancy Risk Assessment Monitoring System and Rhode Island's follow-up Toddlers Wellness Overview Survey distributed to mothers giving birth between 2006 and 2008 were analyzed. Compared with non-depressed mothers, those with any depression following childbirth reported more concerns with their toddlers' receptive language, social-emotional development, and their sleep and feeding behaviors. When adjusted for demographics, persistent depression remained associated with social-emotional (adjusted odds ratio [aOR] = 7.53, 2.78-20.34) and feeding concerns (aOR = 3.13, 1.36-7.22), and current depression was associated with social-emotional concerns (aOR = 2.52, 1.26-5.01). We conclude that pediatric providers should explore maternal mental health as a mediating and potentially modifiable factor beyond the postpartum period when toddlers present with developmental-behavioral challenges.


Assuntos
Depressão Pós-Parto , Depressão , Feminino , Criança , Pré-Escolar , Humanos , Gravidez , Depressão/diagnóstico , Emoções , Mães/psicologia , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/psicologia , Período Pós-Parto/psicologia
2.
Neuropsychopharmacology ; 49(3): 584-592, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37735504

RESUMO

Major depressive disorder (MDD) is a serious psychiatric disorder that in extreme cases can lead to suicide. Evidence suggests that alterations in the kynurenine pathway (KP) contribute to the pathology of MDD. Activation of the KP leads to the formation of neuroactive metabolites, including kynurenic acid (KYNA) and quinolinic acid (QUIN). To test for changes in the KP, postmortem anterior cingulate cortex (ACC) was obtained from the National Institute of Health NeuroBioBank. Gene expression of KP enzymes and relevant neuroinflammatory markers were investigated via RT-qPCR (Fluidigm) and KP metabolites were measured using liquid chromatography-mass spectrometry in tissue from individuals with MDD (n = 44) and matched nonpsychiatric controls (n = 36). We report increased IL6 and IL1B mRNA in MDD. Subgroup analysis found that female MDD subjects had significantly decreased KYNA and a trend decrease in the KYNA/QUIN ratio compared to female controls. In addition, MDD subjects that died by suicide had significantly decreased KYNA in comparison to controls and MDD subjects that did not die by suicide, while subjects that did not die by suicide had increased KYAT2 mRNA, which we hypothesise may protect against a decrease in KYNA. Overall, we found sex- and suicide-specific alterations in the KP in the ACC in MDD. This is the first molecular evidence in the brain of subgroup specific changes in the KP in MDD, which not only suggests that treatments aimed at upregulation of the KYNA arm in the brain may be favourable for female MDD sufferers but also might assist managing suicidal behaviour.


Assuntos
Transtorno Depressivo Maior , Suicídio , Humanos , Feminino , Transtorno Depressivo Maior/metabolismo , Cinurenina , Giro do Cíngulo/metabolismo , Depressão , RNA Mensageiro/metabolismo , Ácido Cinurênico/metabolismo , Ácido Quinolínico
3.
J Psychiatr Res ; 160: 204-209, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36848775

RESUMO

The glutamatergic system may be central to the neurobiology and treatment of major depressive disorder (MDD) and psychosis. Despite the success of N-methyl-D-aspartate receptor (NMDAR) antagonists for the treatment of MDD, little is known regarding the expression of these glutamate receptors in MDD. In this study we measured gene expression, via qRT-PCR, of the major NMDAR subunits, in the anterior cingulate cortex (ACC) in MDD subjects with and without psychosis, and non-psychiatric controls. Overall, GRIN2B mRNA was increased in both MDD with (+32%) and without psychosis (+40%) compared to controls along with a trend increase in GRIN1 mRNA in MDD overall (+24%). Furthermore, in MDD with psychosis there was a significant decrease in the GRIN2A:GRIN2B mRNA ratio (-19%). Collectively these results suggest dysfunction of the glutamatergic system at the gene expression level in the ACC in MDD. Increased GRIN2B mRNA in MDD, along with an altered GRIN2A:GRIN2B ratio in psychotic depression, suggests a disruption to NMDAR composition could be present in the ACC in MDD; this could lead to enhanced signalling via GluN2B-containing NMDARs and greater potential for glutamate excitotoxicity in the ACC in MDD. These results support future research into GluN2B antagonist-based treatments for MDD.


Assuntos
Transtorno Depressivo Maior , Receptores de N-Metil-D-Aspartato , Humanos , Depressão/psicologia , Transtorno Depressivo Maior/genética , Expressão Gênica , Giro do Cíngulo/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , RNA Mensageiro/metabolismo
4.
Front Cell Neurosci ; 16: 1010478, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406747

RESUMO

Cannabidiol (CBD) is a non-intoxicating cannabinoid with antipsychotic-like properties, however it's potential to prevent schizophrenia development has not been thoroughly investigated. Brain maturation during adolescence creates a window where CBD could potentially limit the development of schizophrenia. The neuregulin 1 transmembrane domain heterozygous (Nrg1 TM HET) mutant mouse shows face, predictive, and construct validity for schizophrenia. Here we sought to determine if CBD given in adolescence could prevent the development of the schizophrenia-relevant phenotype, as well as susceptibility to the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) in Nrg1 TM HET mice. Adolescent male Nrg1 mutants and wild type-like (WT) animals were administered 30 mg/kg CBD i.p. daily for seven weeks, and were tested for locomotion, social behavior, sensorimotor gating and cognition, and sensitivity to acute THC-induced behaviors. GAD67, GluA1, and NMDAR1 protein levels were measured in the hippocampus, striatum, and prefrontal cortex. Chronic adolescent CBD increased locomotion in animals regardless of genotype, was anxiolytic, and increased social behavior when animals were tested for their acute THC response. CBD did not alleviate the schizophrenia-relevant hyperlocomotive phenotype of Nrg1 mutants, nor deficits in social behaviors. Nrg1 mutant mice treated with CBD and THC showed no habituation to a startle pulse, suggesting CBD increased vulnerability to the startle habituation-reducing effects of THC in mutant mice. CBD increased levels of GluA1, but reduced levels of GAD67 in the hippocampus of Nrg1 mutants. These results suggest adolescent CBD is not effective as a preventative of schizophrenia-relevant behavioral deficits in mutants and may actually contribute to pathological changes in the brain that increase sensitivity to THC in particular behavioral domains.

6.
Genome Biol ; 23(1): 204, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36167554

RESUMO

BACKGROUND: Many short-read genome assemblies have been found to be incomplete and contain mis-assemblies. The Vertebrate Genomes Project has been producing new reference genome assemblies with an emphasis on being as complete and error-free as possible, which requires utilizing long reads, long-range scaffolding data, new assembly algorithms, and manual curation. A more thorough evaluation of the recent references relative to prior assemblies can provide a detailed overview of the types and magnitude of improvements. RESULTS: Here we evaluate new vertebrate genome references relative to the previous assemblies for the same species and, in two cases, the same individuals, including a mammal (platypus), two birds (zebra finch, Anna's hummingbird), and a fish (climbing perch). We find that up to 11% of genomic sequence is entirely missing in the previous assemblies. In the Vertebrate Genomes Project zebra finch assembly, we identify eight new GC- and repeat-rich micro-chromosomes with high gene density. The impact of missing sequences is biased towards GC-rich 5'-proximal promoters and 5' exon regions of protein-coding genes and long non-coding RNAs. Between 26 and 60% of genes include structural or sequence errors that could lead to misunderstanding of their function when using the previous genome assemblies. CONCLUSIONS: Our findings reveal novel regulatory landscapes and protein coding sequences that have been greatly underestimated in previous assemblies and are now present in the Vertebrate Genomes Project reference genomes.


Assuntos
Genoma , Vertebrados , Animais , Composição de Bases/genética , Cromossomos , Genoma/genética , Análise de Sequência de DNA , Vertebrados/genética
7.
Genome Biol ; 23(1): 205, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36167596

RESUMO

BACKGROUND: False duplications in genome assemblies lead to false biological conclusions. We quantified false duplications in popularly used previous genome assemblies for platypus, zebra finch, and Anna's Hummingbird, and their new counterparts of the same species generated by the Vertebrate Genomes Project, of which the Vertebrate Genomes Project pipeline attempted to eliminate false duplications through haplotype phasing and purging. These assemblies are among the first generated by the Vertebrate Genomes Project where there was a prior chromosomal level reference assembly to compare with. RESULTS: Whole genome alignments revealed that 4 to 16% of the sequences are falsely duplicated in the previous assemblies, impacting hundreds to thousands of genes. These lead to overestimated gene family expansions. The main source of the false duplications is heterotype duplications, where the haplotype sequences were relatively more divergent than other parts of the genome leading the assembly algorithms to classify them as separate genes or genomic regions. A minor source is sequencing errors. Ancient ATP nucleotide binding gene families have a higher prevalence of false duplications compared to other gene families. Although present in a smaller proportion, we observe false duplications remaining in the Vertebrate Genomes Project assemblies that can be identified and purged. CONCLUSIONS: This study highlights the need for more advanced assembly methods that better separate haplotypes and sequence errors, and the need for cautious analyses on gene gains.


Assuntos
Genoma , Genômica , Trifosfato de Adenosina , Animais , Duplicação Gênica , Nucleotídeos , Análise de Sequência de DNA/métodos , Vertebrados/genética
8.
Nat Commun ; 13(1): 4628, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941116

RESUMO

The presence of distinct stem cells that maintain the interfollicular epidermis is highly debated. Here, we report a population of keratinocytes, marked by Thy1, in the basal layer of the interfollicular epidermis. We find that epidermal cells expressing differential levels of Thy1 display distinct transcriptional signatures. Thy1+ keratinocytes do not express T cell markers, express a unique transcriptional profile, cycle significantly slower than basal epidermal progenitors and display significant expansion potential in vitro. Multicolor lineage tracing analyses and mathematical modeling reveal that Thy1+ basal keratinocytes do not compete neutrally alike interfollicular progenitors and contribute long-term to both epidermal replenishment and wound repair. Importantly, ablation of Thy1+ cells strongly impairs these processes, thus indicating the non-redundant function of Thy1+ stem cells in the epidermis. Collectively, these results reveal a distinct stem cell population that plays a critical role in epidermal homeostasis and repair.


Assuntos
Células Epidérmicas , Células-Tronco , Animais , Diferenciação Celular/fisiologia , Epiderme/metabolismo , Queratinócitos/metabolismo , Camundongos , Células-Tronco/metabolismo
9.
Gigascience ; 112022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35946988

RESUMO

BACKGROUND: Studies in vertebrate genomics require sampling from a broad range of tissue types, taxa, and localities. Recent advancements in long-read and long-range genome sequencing have made it possible to produce high-quality chromosome-level genome assemblies for almost any organism. However, adequate tissue preservation for the requisite ultra-high molecular weight DNA (uHMW DNA) remains a major challenge. Here we present a comparative study of preservation methods for field and laboratory tissue sampling, across vertebrate classes and different tissue types. RESULTS: We find that storage temperature was the strongest predictor of uHMW fragment lengths. While immediate flash-freezing remains the sample preservation gold standard, samples preserved in 95% EtOH or 20-25% DMSO-EDTA showed little fragment length degradation when stored at 4°C for 6 hours. Samples in 95% EtOH or 20-25% DMSO-EDTA kept at 4°C for 1 week after dissection still yielded adequate amounts of uHMW DNA for most applications. Tissue type was a significant predictor of total DNA yield but not fragment length. Preservation solution had a smaller but significant influence on both fragment length and DNA yield. CONCLUSION: We provide sample preservation guidelines that ensure sufficient DNA integrity and amount required for use with long-read and long-range sequencing technologies across vertebrates. Our best practices generated the uHMW DNA needed for the high-quality reference genomes for phase 1 of the Vertebrate Genomes Project, whose ultimate mission is to generate chromosome-level reference genome assemblies of all ∼70,000 extant vertebrate species.


Assuntos
Benchmarking , Dimetil Sulfóxido , Animais , DNA/genética , Ácido Edético , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Peso Molecular , Análise de Sequência de DNA/métodos
11.
J Psychiatr Res ; 147: 203-211, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35063739

RESUMO

Evidence, largely obtained from peripheral studies, suggests that alterations in the kynurenine pathway contribute to the aetiology of depression and disorders involving psychosis. Stimulation of the kynurenine pathway leads to the formation of neuroactive metabolites, including kynurenic acid (predominantly in astrocytes) and quinolinic acid (predominantly in microglia), which are antagonists and agonists of the glutamate NMDA receptor, respectively. In this study, we measured gene expression via qRT-PCR of the main kynurenine pathway enzymes in the anterior cingulate cortex (ACC) in people with major depressive disorder and matched controls. In parallel, we tested for diagnostic differences in gene expression of relevant glial markers. We used total RNA isolated from the ACC from depression subjects with psychosis (n = 12) and without psychosis (n = 12), and non-psychiatric controls (n = 12) provided by the Stanley Medical Research Institute. In the ACC, KYAT1 (KAT I), AADAT (KAT II), and the astrocytic SLC1A2 (EAAT2) mRNAs, were significantly increased in depression, when combining those with and without psychosis. The increased KYAT1 and AADAT mRNA indicates that depression is associated with increased activation of the kynurenic acid arm of the kynurenine pathway in the ACC, suggesting an astrocyte response in depression. Considering EAAT2 and KATs increase astrocytic glutamate uptake and production of the NMDA receptor antagonist kynurenic acid, the observed increases of these markers may relate to changes in glutamatergic signalling in depression. These results suggest dysfunction of the kynurenine pathway in the brain in depression and point to the kynurenine pathway as a possible driver of glutamate dysfunction in depression.


Assuntos
Transtorno Depressivo Maior , Transtornos Psicóticos , Astrócitos/metabolismo , Depressão , Transtorno Depressivo Maior/metabolismo , Humanos , Ácido Cinurênico/metabolismo , Cinurenina
12.
BMJ Open ; 12(1): e050540, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34992104

RESUMO

OBJECTIVE: To identify initial diagnoses associated with elevated risk of chronic prescription opioid use. DESIGN: Population-based, retrospective cohort study. SETTING: State of Rhode Island. PARTICIPANTS: Rhode Island residents with an initial opioid prescription dispensed between 1 April 2019 and 31 March 2020. PRIMARY OUTCOME MEASURE: Subsequent chronic prescription opioid use, defined as receiving 60 or more days' supply of opioids in the 90 days following an initial opioid prescription. RESULTS: Among the 87 055 patients with an initial opioid prescription, 3199 (3.7%) subsequently became chronic users. Patients who become chronic users tended to receive a longer days' supply, greater quantity dispensed, but a lower morphine milligram equivalents on the initial opioid prescription. Patients prescribed an initial opioid prescription for diseases of the musculoskeletal system and connective tissue (adjusted OR (aOR): 5.9, 95% CI: 4.7 to 7.6), diseases of the nervous system (aOR: 6.3, 95% CI: 4.9 to 8.0) and neoplasms (aOR: 5.6, 95% CI: 4.2 to 7.5) had higher odds of subsequent chronic prescription opioid use, compared with a referent group that included all diagnosis types with fewer than 15 chronic opioid users, after adjusting for confounders. CONCLUSIONS: By focusing interventions and prescribing guidelines on specific types of diagnoses that carry a high risk of chronic prescription opioid use and diagnoses that would benefit equally or more from alternative management approaches, states and healthcare organisations may more efficiently decrease inappropriate opioid prescribing while improving the quality of patient care.


Assuntos
Analgésicos Opioides , Padrões de Prática Médica , Analgésicos Opioides/uso terapêutico , Estudos de Coortes , Prescrições de Medicamentos , Humanos , Estudos Retrospectivos , Rhode Island/epidemiologia
13.
Public Health Rep ; 136(1_suppl): 24S-30S, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34726976

RESUMO

The Rhode Island Department of Health (RIDOH) uses emergency department data to monitor nonfatal opioid overdoses in Rhode Island. In April 2019, RIDOH detected an increase in nonfatal opioid overdoses in Woonsocket, Rhode Island, and sent an alert to state and local partners (eg, fire departments, emergency departments, faith leaders) with guidance on how to respond. To guide community-level, strategic response efforts, RIDOH analyzed surveillance data to identify overdose patterns, populations, and geographic areas most affected. During April-June 2019, nonfatal opioid overdoses in Woonsocket increased 463% (from 13 to 73) when compared with the previous 3 months. Because of the sustained increase in nonfatal opioid overdoses, RIDOH brought together community partners at a meeting in June 2019 to discuss RIDOH opioid overdose data and coordinate next steps. Data analyses were essential to framing the discussion and allowed community partners at the event to identify an unexpected increase in cocaine-involved nonfatal opioid overdoses in Woonsocket. Many patients with cocaine-involved nonfatal overdoses also had fentanyl in their system, and input from community partners suggested that many patients were unaware of using fentanyl. Community response actions included targeting harm reduction services (eg, distribution of naloxone, mobile needle exchange); deploying peer recovery support specialists to overdose hotspots to connect people to treatment and recovery resources; placing harm reduction messaging in high-traffic areas; and targeted social media messaging. After the meeting, nonfatal opioid overdoses returned to pre-outbreak levels. This case study provides an example of how timely opioid overdose data can be effectively used to detect a spike in nonfatal opioid overdoses and inform a strategic, community-level response.


Assuntos
Apoio Comunitário , Overdose de Drogas/prevenção & controle , Fatores de Tempo , Adulto , Overdose de Drogas/epidemiologia , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rhode Island/epidemiologia
14.
Public Health Rep ; 136(1_suppl): 40S-46S, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34726979

RESUMO

OBJECTIVE: No case definition exists that allows public health authorities to accurately identify opioid overdoses using emergency medical services (EMS) data. We developed and evaluated a case definition for suspected nonfatal opioid overdoses in EMS data. METHODS: To identify suspected opioid overdose-related EMS runs, in 2019 the Rhode Island Department of Health (RIDOH) developed a case definition using the primary impression, secondary impression, selection of naloxone in the dropdown field for medication given, indication of medication response in a dropdown field, and keyword search of the report narrative. We developed the case definition with input from EMS personnel and validated it using an iterative process of random medical record review. We used naloxone administration in consideration with other factors to avoid misclassification of opioid overdoses. RESULTS: In 2018, naloxone was administered during 2513 EMS runs in Rhode Island, of which 1501 met our case definition of a nonfatal opioid overdose. Based on a review of 400 randomly selected EMS runs in which naloxone was administered, the RIDOH case definition accurately identified 90.0% of opioid overdoses and accurately excluded 83.3% of non-opioid overdose-related EMS runs. Use of the case definition enabled analyses that identified key patterns in overdose locations, people who experienced repeat overdoses, and the creation of hotspot maps to inform outbreak detection and response. PRACTICE IMPLICATIONS: EMS data can be an effective tool for monitoring overdoses in real time and informing public health practice. To accurately identify opioid overdose-related EMS runs, the use of a comprehensive case definition is essential.


Assuntos
Defesa Civil/normas , Serviços Médicos de Emergência/estatística & dados numéricos , Overdose de Opiáceos/diagnóstico , Fatores de Tempo , Adulto , Defesa Civil/estatística & dados numéricos , Serviços Médicos de Emergência/métodos , Humanos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Overdose de Opiáceos/epidemiologia , Rhode Island
15.
Pregnancy Hypertens ; 25: 249-254, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34320425

RESUMO

OBJECTIVE: Both small for gestational age (SGA) birthweight and pregnancies complicated by maternal hypertension (HTN) are independently associated with poorer childhood learning outcomes, however the relative contribution of each remains unknown. STUDY DESIGN: A retrospective cohort was created in which 2014-2017 third grade Rhode Island Department of Education data were linked to Rhode Island Department of Health birth certificate data. The study population was composed of non-anomalous, singleton births between 22- and 42-weeks' gestation. Reading and math proficiency were compared among four groups: 1) appropriate for gestational age (AGA) and no maternal HTN (referent), 2) AGA with HTN, 3) SGA without HTN and 4) SGA with HTN. MAIN OUTCOME MEASURES: Bivariable and multivariable log-binomial regression were used to examine the association between subject proficiency and pregnancy complication, adjusting for potential confounders. RESULTS: Of the 23,097 who met inclusion criteria, 1004 (4%) were AGA with HTN, 1575 (7%) were SGA without HTN and 176 (1%) were SGA with HTN. Overall, when adjusted for maternal age, gestational age, sex and socioeconomic factors, only children born SGA without HTN had reduced reading proficiency (relative risk (RR) 0.86 95% confidence interval (CI) 0.78, 0.92) and math proficiency (RR 0.88 95% CI 0.82, 0.94) compared to children born AGA without HTN. CONCLUSION: In a diverse, statewide cohort, only SGA without HTN was associated with lower reading and math proficiency compared to uncomplicated pregnancies. This suggests that only decreased fetal growth from causes other than HTN is associated with risk of poorer school-age outcomes, and has implications for early resource allocation.


Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Transtornos do Neurodesenvolvimento/epidemiologia , Pré-Eclâmpsia , Diagnóstico Pré-Natal , Adulto , Criança , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Humanos , Recém-Nascido , Transtornos do Neurodesenvolvimento/economia , Transtornos do Neurodesenvolvimento/etiologia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Rhode Island/epidemiologia , Adulto Jovem
16.
Neurosci Biobehav Rev ; 127: 917-927, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34029552

RESUMO

Major depression is a serious psychiatric disorder, occurring in up to 20 % of the population. Despite its devastating burden, the neurobiological changes associated with depression are not fully understood. A growing body of evidence suggests the kynurenine pathway is implicated in the pathophysiology of depression. In this review, we bring together the literature examining elements of the kynurenine pathway in depression and explore the implications for the pathophysiology and treatment of depression, while highlighting the gaps in the current knowledge. Current research indicates an increased potential for neurotoxic activity of the kynurenine pathway in peripheral blood samples but an increased activation of the putative neuroprotective arm in some brain regions in depression. The disconnect between these findings requires further investigation, with a greater research effort on elucidating the central effects of the kynurenine pathway in driving depression symptomology. Research investigating the benefits of targeting the kynurenine pathway centred on human brain findings and the heterogenous subtypes of depression will help guide the identification of effective drug targets in depression.


Assuntos
Transtorno Depressivo Maior , Cinurenina , Encéfalo , Depressão , Humanos
17.
Genome Biol ; 22(1): 120, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33910595

RESUMO

BACKGROUND: Modern sequencing technologies should make the assembly of the relatively small mitochondrial genomes an easy undertaking. However, few tools exist that address mitochondrial assembly directly. RESULTS: As part of the Vertebrate Genomes Project (VGP) we develop mitoVGP, a fully automated pipeline for similarity-based identification of mitochondrial reads and de novo assembly of mitochondrial genomes that incorporates both long (> 10 kbp, PacBio or Nanopore) and short (100-300 bp, Illumina) reads. Our pipeline leads to successful complete mitogenome assemblies of 100 vertebrate species of the VGP. We observe that tissue type and library size selection have considerable impact on mitogenome sequencing and assembly. Comparing our assemblies to purportedly complete reference mitogenomes based on short-read sequencing, we identify errors, missing sequences, and incomplete genes in those references, particularly in repetitive regions. Our assemblies also identify novel gene region duplications. The presence of repeats and duplications in over half of the species herein assembled indicates that their occurrence is a principle of mitochondrial structure rather than an exception, shedding new light on mitochondrial genome evolution and organization. CONCLUSIONS: Our results indicate that even in the "simple" case of vertebrate mitogenomes the completeness of many currently available reference sequences can be further improved, and caution should be exercised before claiming the complete assembly of a mitogenome, particularly from short reads alone.


Assuntos
Duplicação Gênica , Genoma Mitocondrial , Genômica , Sequências Repetitivas de Ácido Nucleico , Vertebrados/genética , Animais , Biologia Computacional/métodos , Biologia Computacional/normas , Evolução Molecular , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala
18.
Am J Obstet Gynecol MFM ; 2(4): 100221, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33345929

RESUMO

BACKGROUND: Operative vaginal delivery rates continue to drop nationally with many citing neonatal safety concerns as a primary driver of this decrease. Previous evidence on short-term neonatal outcomes does not support this concern. OBJECTIVE: This study aimed to better understand the impact of delivery mode on childhood educational outcomes. STUDY DESIGN: A statewide retrospective cohort was created in which third grade Rhode Island Department of Education data for 2014 to 2017 were linked to Rhode Island Department of Health birth certificate data. Children's third grade reading and math proficiencies were compared by the mode of delivery listed in their birth certificates. The study population was limited to children who were term, singleton births without congenital anomalies. The mode of delivery was classified as operative vaginal (forceps or vacuum), primary cesarean, or spontaneous vaginal delivery. Children born via repeat cesarean delivery were excluded. Bivariate analyses were conducted to assess differences in demographic variables between mothers and children by mode of delivery and between reading and math proficiencies and mode of delivery. Bivariable and multivariable log-binomial regression was used to examine the association between subject proficiency and predictors including mode of delivery, gestational age, sex, race/ethnicity, and lunch subsidy. RESULTS: Of the 18,247 children who met the inclusion criteria, 6% were delivered by operative vaginal delivery, 19% by primary cesarean delivery, and the remaining 75% by spontaneous vaginal delivery. After adjustment for confounders including gestational age at delivery, child's race/ethnicity, sex, and socioeconomic factors, there was no difference in reading proficiency (adjusted risk ratio, 1.03; 95% confidence interval, 0.96-1.10) or math proficiency (adjusted risk ratio, 1.01; 95% confidence interval, 0.95-1.08) in those born by operative vaginal delivery compared with primary cesarean delivery, and no difference was found in either proficiency when spontaneous vaginal delivery was compared with primary cesarean delivery (reading, adjusted risk ratio, 0.97; 95% confidence interval, 0.93-1.01; math, adjusted risk ratio, 0.98; 95% confidence interval, 0.94-1.01). CONCLUSION: Operative vaginal delivery was not associated with differences in later childhood educational outcomes after adjusting for baseline differences. This should assuage previous concerns about long-term safety outcomes after operative vaginal delivery and may assist in shared decision making when operative vaginal or primary cesarean delivery is being considered.


Assuntos
Cesárea , Parto Obstétrico , Criança , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , Rhode Island
19.
JAMA Netw Open ; 3(4): e202503, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32275323

RESUMO

Importance: Although labor induction at 39 weeks of gestation has been shown to reduce the number of cesarean deliveries, compared with expectant management, without increasing neonatal morbidity in nulliparous, low-risk women, the association between induction at 39 weeks and longer-term childhood cognitive outcomes is not certain. Objective: To evaluate educational outcomes of children born by induction at 39 or 40 weeks compared with those whose mothers were expectantly managed beyond those weeks. Design, Setting, and Participants: This statewide cohort study was conducted in Rhode Island. The participants included children of nulliparous women who were born at 39 weeks of gestation or later and then completed third-grade math and reading tests during the 2014 to 2017 academic year. Data analysis was performed from July 2019 to October 2019. Exposures: Induction of labor compared with expectant management. Main Outcomes and Measures: Third-grade math and reading test scores and proficiency (based on achievement level) among children born after induction in the 39th or 40th week were compared with scores for those who remained in utero beyond that same gestational week. The hypothesis was that induction in the 39th or 40th week would not be associated with differences in math or reading scores or proficiency compared with expectant management past the 39th or 40th week of gestation. Results: Of the 6393 children meeting the inclusion criteria (mean [SD] age, 8.00 [0.22] years; 3208 boys [50.2%]; 376 [5.8%] black; 1280 [22.0%] Hispanic), 455 were delivered by induction in the 39th week and 610 were delivered by induction in the 40th week. There were no differences in mean math or reading test scores or in the frequency of math or reading proficiency between children delivered by induction at 39 or 40 weeks compared with those whose mothers were expectantly managed (overall mean [SD] math score, 744 [33]; overall mean [SD] reading score, 743 [38]; 2945 children [46%] achieved proficiency in math and 2833 [44%] achieved proficiency in reading). After adjusting for plausible confounders (race/ethnicity, maternal education, hypertension, diabetes, and socioeconomic status), induction continued to be associated with similar proficiency in math and reading compared with expectant management. For children born by induction at 39 weeks, the adjusted relative risks were 1.07 (95% CI, 0.97-1.18) for math proficiency and 0.98 (95% CI, 0.88-1.08) for reading proficiency. For children born by induction at 40 weeks, the adjusted relative risks were 0.97 (95% CI, 0.88-1.08) for math proficiency and 0.98 (95% CI, 0.89-1.08) for reading proficiency. Conclusions and Relevance: These findings suggest that the offspring of nulliparous women for whom labor is induced at 39 or 40 weeks have similar third-grade educational outcomes compared with the offspring of mothers who underwent expectant management past those gestational ages.


Assuntos
Desempenho Acadêmico/estatística & dados numéricos , Trabalho de Parto Induzido/estatística & dados numéricos , Conduta Expectante/estatística & dados numéricos , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Gravidez , Rhode Island
20.
R I Med J (2013) ; 103(1): 21-24, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013299

RESUMO

BACKGROUND: The Rhode Island Department of Health (RIDOH) has administered the Health Information Technology (HIT) Survey since 2009 to report clinician-level process measures relating to HIT adoption and use. METHODS: RIDOH administers the Rhode Island HIT Survey to all licensed independent practitioners. Descriptive analyses examined HIT adoption and the clinician experience working with HIT. RESULTS: Most physician and Advanced Practice Provider (APP) respondents report using an EHR (92.5% and 94.3%) and e-prescribing medications (84.1% and 81.6%). Less than half of physicians (40.9% or n=565) and APPs (35.4% or n=195) who prescribe controlled substances currently submit controlled substance prescriptions electronically. A higher percentage of physicians, compared to APPs, reported experiencing HIT-related stress (80.9% and 66.6%). The overall prevalence of physicians reporting symptoms of burnout was 29.7% (n=539) but varied between specialties. DISCUSSION: As of 2019, the majority of Rhode Island physicians have adopted EHRs and e-prescribing. Adoption plateaued after 2012, and challenges persist in integrating existing technology into practice.


Assuntos
Esgotamento Profissional/etiologia , Registros Eletrônicos de Saúde , Informática Médica , Médicos/psicologia , Prescrição Eletrônica/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Humanos , Estresse Ocupacional , Rhode Island
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