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1.
J Gastrointest Surg ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38575464

RESUMO

BACKGROUND: Disease-modifying anti-inflammatory bowel disease drugs (DMAIDs) revolutionized the management of ulcerative colitis (UC). This study assessed the relationship between the number and timing of drugs used to treat UC and the risk of colectomy and postoperative complications. METHODS: This was a retrospective review of adult patients with UC treated with disease-modifying drugs between 2005 and 2020 in the MarketScan database. Landmark and time-varying regression analyses were used to analyze risk of surgical resection. Multivariable Cox regression analysis was used to determine risk of postoperative complications, emergency room visits, and readmissions. RESULTS: A total of 12,193 patients with UC and treated with disease-modifying drugs were identified. With a median follow-up time of 1.7 years, 23.8% used >1 drug, and 8.3% of patients required surgical resection. In landmark analyses, using 2 and ≥3 drugs before the landmark date was associated with higher incidence of surgery for each landmark than 1 drug. Multivariable Cox regression showed hazard ratio (95% CIs) of 4.22 (3.59-4.97), 11.7 (9.01-15.3), and 22.9 (15.0-34.9) for using 2, 3, and ≥4 drugs, respectively, compared with using 1 DMAID. That risk was constant overtime. The number of drugs used preoperatively was not associated with an increased postoperative risk of any complication, emergency room visits, or readmission. CONCLUSION: The use of multiple disease-modifying drugs in UC is associated with an increased risk of surgical resection with each additional drug. This provides important prognostic data and highlights the importance of patient counseling with minimal concern regarding risk of postoperative morbidity for additional drugs.

2.
Dis Model Mech ; 17(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38602028

RESUMO

Duchenne muscular dystrophy (DMD) is a devastating monogenic skeletal muscle-wasting disorder. Although many pharmacological and genetic interventions have been reported in preclinical studies, few have progressed to clinical trials with meaningful benefit. Identifying therapeutic potential can be limited by availability of suitable preclinical mouse models. More rigorous testing across models with varied background strains and mutations can identify treatments for clinical success. Here, we report the generation of a DMD mouse model with a CRISPR-induced deletion within exon 62 of the dystrophin gene (Dmd) and the first generated in BALB/c mice. Analysis of mice at 3, 6 and 12 months of age confirmed loss of expression of the dystrophin protein isoform Dp427 and resultant dystrophic pathology in limb muscles and the diaphragm, with evidence of centrally nucleated fibers, increased inflammatory markers and fibrosis, progressive decline in muscle function, and compromised trabecular bone development. The BALB/c.mdx62 mouse is a novel model of DMD with associated variations in the immune response and muscle phenotype, compared with those of existing models. It represents an important addition to the preclinical model toolbox for developing therapeutic strategies.


Assuntos
Modelos Animais de Doenças , Distrofina , Camundongos Endogâmicos BALB C , Músculo Esquelético , Distrofia Muscular de Duchenne , Animais , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/genética , Distrofina/metabolismo , Distrofina/genética , Músculo Esquelético/patologia , Músculo Esquelético/metabolismo , Camundongos Endogâmicos mdx , Camundongos , Éxons/genética , Masculino , Fibrose , Fenótipo
3.
Sci Rep ; 14(1): 8876, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632329

RESUMO

Classifying diabetes at diagnosis is crucial for disease management but increasingly difficult due to overlaps in characteristics between the commonly encountered diabetes types. We evaluated the prevalence and characteristics of youth with diabetes type that was unknown at diagnosis or was revised over time. We studied 2073 youth with new-onset diabetes (median age [IQR] = 11.4 [6.2] years; 50% male; 75% White, 21% Black, 4% other race; overall, 37% Hispanic) and compared youth with unknown versus known diabetes type, per pediatric endocrinologist diagnosis. In a longitudinal subcohort of patients with data for ≥ 3 years post-diabetes diagnosis (n = 1019), we compared youth with steady versus reclassified diabetes type. In the entire cohort, after adjustment for confounders, diabetes type was unknown in 62 youth (3%), associated with older age, negative IA-2 autoantibody, lower C-peptide, and no diabetic ketoacidosis (all, p < 0.05). In the longitudinal subcohort, diabetes type was reclassified in 35 youth (3.4%); this was not statistically associated with any single characteristic. In sum, among racially/ethnically diverse youth with diabetes, 6.4% had inaccurate diabetes classification at diagnosis. Further research is warranted to improve accurate diagnosis of pediatric diabetes type.


Assuntos
Diabetes Mellitus Tipo 1 , Erros de Diagnóstico , Adolescente , Criança , Feminino , Humanos , Masculino , Peptídeo C , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Cetoacidose Diabética/diagnóstico , Prevalência
4.
J Surg Res ; 295: 399-406, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38070253

RESUMO

INTRODUCTION: While minimally invasive surgery (MIS) approaches are commonly utilized in the elective surgical setting for pediatric ulcerative colitis (UC), their role in urgent and emergent disease is less clear. We aim to assess trends in the surgical approaches for pediatric UC patients requiring urgent and emergent colectomies and their associated outcomes. METHODS: Retrospective review of 81 pediatric UC patients identified in National Surgical Quality Improvement Program Pediatric who underwent urgent or emergent colectomy (2012-2019). Trends in approach were assessed using linear regression. Patient characteristics and clinical outcomes were stratified by approach and compared using standard univariate statistics. Multivariable analysis was used to model the influence of covariates on postoperative length of stay. RESULTS: The proportion of MIS cases increased by 5.53% per year (P = 0.01) over the study interval. Sixty-three patients (77.8%) received MIS resections and 18 patients (22.2%) received open resections. Patients undergoing open colectomies were younger and had a higher proportion of preoperative conditions, most notably preoperative sepsis (27.8% versus 4.8%, P = 0.01), and higher American Society of Anesthesiologists [III-IV] classification (83.3% versus 58.8%, P = 0.004). Mean operative time was comparable (open, 173.6 versus MIS, 206.1 min). In the univariate analysis, open approach was associated with increased postoperative length of stay (13.1 versus 7.2 d, P = 0.002). However, after adjusting for confounders, there was no significant difference. CONCLUSIONS: There has been a steady increase in the adoption of laparoscopy in urgent and emergent colectomy for pediatric UC. Short-term outcomes between approaches appear comparable.


Assuntos
Colite Ulcerativa , Laparoscopia , Humanos , Criança , Colite Ulcerativa/cirurgia , Colectomia/efeitos adversos , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
5.
J Pharmacol Exp Ther ; 388(2): 301-312, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-37827702

RESUMO

Organophosphate (OP) poisoning can trigger cholinergic crisis, a life-threatening toxidrome that includes seizures and status epilepticus. These acute toxic responses are associated with persistent neuroinflammation and spontaneous recurrent seizures (SRS), also known as acquired epilepsy. Blood-brain barrier (BBB) impairment has recently been proposed as a pathogenic mechanism linking acute OP intoxication to chronic adverse neurologic outcomes. In this review, we briefly describe the cellular and molecular components of the BBB, review evidence of altered BBB integrity following acute OP intoxication, and discuss potential mechanisms by which acute OP intoxication may promote BBB dysfunction. We highlight the complex interplay between neuroinflammation and BBB dysfunction that suggests a positive feedforward interaction. Lastly, we examine research from diverse models and disease states that suggest mechanisms by which loss of BBB integrity may contribute to epileptogenic processes. Collectively, the literature identifies BBB impairment as a convergent mechanism of neurologic disease and justifies further mechanistic research into how acute OP intoxication causes BBB impairment and its role in the pathogenesis of SRS and potentially other long-term neurologic sequelae. Such research is critical for evaluating BBB stabilization as a neuroprotective strategy for mitigating OP-induced epilepsy and possibly seizure disorders of other etiologies. SIGNIFICANCE STATEMENT: Clinical and preclinical studies support a link between blood-brain barrier (BBB) dysfunction and epileptogenesis; however, a causal relationship has been difficult to prove. Mechanistic studies to delineate relationships between BBB dysfunction and epilepsy may provide novel insights into BBB stabilization as a neuroprotective strategy for mitigating epilepsy resulting from acute organophosphate (OP) intoxication and non-OP causes and potentially other adverse neurological conditions associated with acute OP intoxication, such as cognitive impairment.


Assuntos
Epilepsia , Intoxicação por Organofosfatos , Ratos , Animais , Humanos , Barreira Hematoencefálica , Encéfalo/patologia , Doenças Neuroinflamatórias , Organofosfatos , Ratos Sprague-Dawley , Epilepsia/induzido quimicamente , Doença Aguda
6.
PLoS One ; 18(12): e0294180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38051746

RESUMO

OBJECTIVE: This is the first systematic review aims to build the evidence for the impact of accreditation on quality improvement of healthcare services, as well as identify and develop an understanding of the contextual factors influencing accreditation implementation in the hospital setting through the lens of Normalisation Process Theory (NPT). DATA SOURCES: Data were gathered from five databases; MEDLINE, PUBMED, EMBASE, CINAHL, and the Cochrane Library. And supplemental sources. STUDY DESIGN: This systematic review is reported following PRISMA guidelines with a quality assessment. Data were analysed using a thematic analysis guided by the NPT theoretical framework. DATA COLLECTION/EXTRACTION METHODS: Data were extracted and summarized using prespecified inclusion/exclusion criteria and a data extraction sheet encompassing all necessary information about the studies included in the review. PRINCIPAL FINDINGS: There are inconsistent findings about the impact of accreditation on improving healthcare quality and outcomes, and there is scant evidence about its effectiveness. The findings also provide valuable insights into the key factors that may influence hospital accreditation implementation and develop a better understanding of their potential implications. Using the NPT shows a growing emphasis on the enactment work of the accreditation process and how this may drive improving the quality of healthcare services. However, little focus is given to accreditation's effects on health professionals' roles and responsibilities, strategies and ways for engaging health professionals for effective implementation, and ensuring that the goals and potential benefits of accreditation are made clear and transparent through ongoing evaluation and feedback to all health professionals involved in the accreditation process. CONCLUSIONS: While there are contradictory findings about the impact of accreditation on improving the quality of healthcare services, accreditation continues to gain acceptance internationally as a quality assurance tool to support best practices in evaluating the quality outcomes of healthcare delivered. Policymakers, healthcare organisations, and researchers should proactively consider a set of key factors for the future implementation of accreditation programmes if they are to be effectively implemented and sustained within the hospital setting. Systematic review registration: International Prospective Register of Systematic Reviews PROSPERO 2020 CRD42020172390 Available from: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=172390.


Assuntos
Atenção à Saúde , Melhoria de Qualidade , Qualidade da Assistência à Saúde , Hospitais , Acreditação
7.
EMBO J ; 42(23): e115008, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37964598

RESUMO

The main goals and challenges for the life science communities in the Open Science framework are to increase reuse and sustainability of data resources, software tools, and workflows, especially in large-scale data-driven research and computational analyses. Here, we present key findings, procedures, effective measures and recommendations for generating and establishing sustainable life science resources based on the collaborative, cross-disciplinary work done within the EOSC-Life (European Open Science Cloud for Life Sciences) consortium. Bringing together 13 European life science research infrastructures, it has laid the foundation for an open, digital space to support biological and medical research. Using lessons learned from 27 selected projects, we describe the organisational, technical, financial and legal/ethical challenges that represent the main barriers to sustainability in the life sciences. We show how EOSC-Life provides a model for sustainable data management according to FAIR (findability, accessibility, interoperability, and reusability) principles, including solutions for sensitive- and industry-related resources, by means of cross-disciplinary training and best practices sharing. Finally, we illustrate how data harmonisation and collaborative work facilitate interoperability of tools, data, solutions and lead to a better understanding of concepts, semantics and functionalities in the life sciences.


Assuntos
Disciplinas das Ciências Biológicas , Pesquisa Biomédica , Software , Fluxo de Trabalho
8.
Microbiol Resour Announc ; 12(10): e0071823, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37772859

RESUMO

We report the genomes of two viruses with siphovirus morphology, OtterstedtS21 and Patos, from Albany, New York, using Gordonia rubripertincta. The genomes of OtterstedtS21 and Patos are ~68 kbp long with 58% GC content. Both phages group with cluster DV based on gene content similarity to phages in the Actinobacteriophage database.

9.
Hum Reprod ; 38(11): 2166-2174, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37697711

RESUMO

STUDY QUESTION: How do adult offspring in planned lesbian-parent families feel about and relate to their donor (half) sibling(s) (DS)? SUMMARY ANSWER: A majority of offspring had found DS and maintained good ongoing relationships, and all offspring (regardless of whether a DS had been identified) were satisfied with their knowledge of and contact level with the DS. WHAT IS KNOWN ALREADY: The first generation of donor insemination offspring of intended lesbian-parent families is now in their 30s. Coincident with this is an increased use of DNA testing and genetic ancestry websites, facilitating the discovery of donor siblings from a common sperm donor. Few studies of offspring and their DS include sexual minority parent (SMP) families, and only sparse data separately analyze the offspring of SMP families or extend the analyses to established adult offspring. STUDY DESIGN, SIZE, DURATION: This cohort study included 75 adult offspring, longitudinally followed since conception in lesbian-parent families. Quantitative analyses were performed from online surveys of the offspring in the seventh wave of the 36-year study, with a 90% family retention rate. The data were collected from March 2021 to November 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were 30- to 33-year-old donor insemination offspring whose lesbian parents enrolled in a US prospective longitudinal study when these offspring were conceived. Offspring who knew of a DS were asked about their numbers found, characteristics or motivations for meeting, DS terminology, relationship quality and maintenance, and impact of the DS contact on others. All offspring (with or without known DS) were asked about the importance of knowing if they have DS and their terminology, satisfaction with information about DS, and feelings about future contact. MAIN RESULTS AND THE ROLE OF CHANCE: Of offspring, 53% (n = 40) had found DS in modest numbers, via a DS or sperm bank registry in 45% of cases, and most of these offspring had made contact. The offspring had their meeting motivations fulfilled, viewed the DS as acquaintances more often than siblings or friends, and maintained good relationships via meetings, social media, and cell phone communication. They disclosed their DS meetings to most relatives with neutral impact. The offspring, whether with known or unknown DS, felt neutral about the importance of knowing if they had DS, were satisfied with what they knew (or did not know) of the DS, and were satisfied with their current level of DS contact. This study is the largest, longest-running longitudinal study of intended lesbian-parent families and their offspring, and due to its prospective nature, is not biased by over-sampling offspring who were already satisfied with their DS. LIMITATIONS, REASONS FOR CAUTION: The sample was from the USA, and mostly White, highly educated individuals, not representative of the diversity of donor insemination offspring of lesbian-parent families. WIDER IMPLICATIONS OF THE FINDINGS: While about half of the offspring found out about DS, the other half did not. Regardless of knowing of a DS, these adult offspring of lesbian parents were satisfied with their level of DS contact. Early disclosure and identity formation about being donor-conceived in a lesbian-parent family may distinguish these study participants from donor insemination offspring and adoptees in the general population, who may be more compelled to seek genetic relatives. The study participants who sought DS mostly found a modest number of them, in contrast to reports in studies that have found large numbers of DS. This may be because one-third of study offspring had donors known to the families since conception, who may have been less likely to participate in commercial sperm banking or internet donation sites, where quotas are difficult to enforce or nonexistent. The study results have implications for anyone considering gamete donation, gamete donors, donor-conceived offspring, and/or gamete banks, as well as the medical and public policy professionals who advise them. STUDY FUNDING/COMPETING INTEREST(S): No funding was provided for this project. The authors have no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Inseminação Artificial Heteróloga , Minorias Sexuais e de Gênero , Adulto , Feminino , Humanos , Masculino , Relações entre Irmãos , Estudos de Coortes , Estudos Longitudinais , Filhos Adultos , Estudos Prospectivos , Sêmen , Doadores de Tecidos , Pais
10.
Indian J Gastroenterol ; 42(5): 694-700, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37648878

RESUMO

BACKGROUND: Anal adenocarcinoma (AA) is a rare malignancy with decreased survival compared to rectal adenocarcinoma (RA). However, AA continues to be treated with similar algorithms compared to rectal cancer with minimal data regarding the efficacy of these treatment algorithms. METHODS: A retrospective chart review of patients with non-metastatic AA at a single tertiary-care institution from 1995 to 2020. This cohort was matched 2:1 to a group of RA patients for comparison. The primary outcome of interest was overall survival rates. RESULTS: Sixteen patients with stages I-III AA were matched to a cohort of RA. There were no significant differences between the cohorts with regard to patient demographics, comorbidities, disease stage or histologic features. There were also no significant differences in treatment modalities between the two cohorts with a majority undergoing multimodal therapy with chemoradiation and surgery. All patients with AA demonstrated significantly worse survival than all patients with rectal adenocarcinoma (five-year survival 47.7% vs. 82.3%, respectively. p < 0.05). When looking at a sub-group of patients who underwent combination chemoradiation and surgery from each cohort, anal adenocarcinoma continued to exhibit lower overall survival (five-year survival 41.6% and 86.4%, respectively. p < 0.05). In a multi-variable model that adjusted for location, American Joint Committee on Cancer (AJCC) stage and treatment pathway, tumor location in the anal canal was an independent predictor of overall survival (Hazard ratio [HR] 2.7, p < 0.05). CONCLUSION: AA has worse survival as compared to RA despite similar treatment. This study highlights the need to evaluate the current classification and treatment pathways to improve outcomes.


Assuntos
Adenocarcinoma , Neoplasias do Ânus , Neoplasias Retais , Humanos , Estudos Retrospectivos , Prognóstico , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/cirurgia , Adenocarcinoma/terapia , Resultado do Tratamento , Taxa de Sobrevida
11.
J Reprod Infant Psychol ; : 1-14, 2023 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-37394815

RESUMO

AIM: The present study examined how adult offspring of lesbian parents relate to their anonymous, open-identity, or known donors. DESIGN: An online survey of 75 donor-conceived offspring of lesbian parents, aged 30-33 years, participating in Wave 7 of a U.S. 36-year longitudinal study of planned lesbian-parent families was conducted. Offspring were asked about donor type, motivations for contacting the donor, terminology for the donor, relationship quality, means of relationship maintenance, impact of donor contact on offspring's other family members, and their feelings about the donor. RESULTS: Twenty offspring with anonymous donors and 15 with open-identity donors whom they had not contacted felt comfortable not knowing their donors. Forty offspring knew their donors - anonymous, contacted through an online registry (n = 7), open-identity, contacted (n = 9), or known since childhood (n = 24). Offspring who had contacted their donor since age 18 had their motivations fulfilled after contact, got along well with him, did not view him as a relative, and had told most family members about their contact, without detriment. Whether the donor was unknown or known at this stage of their lives, most offspring were satisfied with their contact level. CONCLUSION: This cohort of donor-conceived offspring of lesbian parents was among the first to reach adulthood during a time of technological advances in DNA testing, giving access to anonymous donors via online registries. The results inform donors, families, mental health providers, medical providers and public policymakers, on whether, how, and to what degree donor-conceived offspring optimally make donor contact.

12.
Res Sq ; 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37293006

RESUMO

Classifying diabetes at diagnosis is crucial for disease management but increasingly difficult due to overlaps in characteristics between the commonly encountered diabetes types. We evaluated the prevalence and characteristics of youth with diabetes type that was unknown at diagnosis or was revised over time. We studied 2073 youth with new-onset diabetes (median age [IQR]=11.4 [6.2] years; 50% male; 75% White, 21% Black, 4% other race; overall, 37% Hispanic) and compared youth with unknown versus known diabetes type, per pediatric endocrinologist diagnosis. In a longitudinal subcohort of patients with data for ≥3 years post-diabetes diagnosis (n=1019), we compared youth with unchanged versus changed diabetes classification. In the entire cohort, after adjustment for confounders, diabetes type was unknown in 62 youth (3%), associated with older age, negative IA-2 autoantibody, lower C-peptide, and no diabetic ketoacidosis (all, p<0.05). In the longitudinal subcohort, diabetes classification changed in 35 youth (3.4%); this was not statistically associated with any single characteristic. Having unknown or revised diabetes type was associated with less continuous glucose monitor use on follow-up (both, p<0.004). In sum, among racially/ethnically diverse youth with diabetes, 6.5% had imprecise diabetes classification at diagnosis. Further research is warranted to improve accurate diagnosis of pediatric diabetes type.

13.
J Appl Physiol (1985) ; 135(1): 77-87, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37262103

RESUMO

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations or deletions in the dystrophin gene, for which there remains no cure. As DMD patients also develop bone fragility because of muscle weakness and immobilization, better understanding of the pathophysiological mechanisms of dystrophin deficiency will help develop therapies to improve musculoskeletal health. Since alterations in muscle phenotype can influence bone structure, we investigated whether modifying muscle contractile activity through low-frequency stimulation (LFS) could alter bone architecture in mouse models of DMD. We tested the hypothesis that increasing muscle contractile activity could influence bone mass and structure in dystrophin-deficient (mdx) and dystrophin- and utrophin-deficient (dko) dystrophic mice. Tibial bone structure in dko mice was significantly different from that in mdx and wild-type (C57BL/10) control mice. Effects of LFS on bone architecture differed between dystrophic and healthy mice, with LFS thinning cortical bone in both dystrophic models. Bone mass was maintained in LFS-treated healthy mice, with a reduced proportion of high-density bone and concomitant increase in low-density bone. LFS-treated dko mice exhibited a net deficit in cortical thickness and reduced high-density bone but no equivalent increase in low-density bone. These alterations in bone structure and mineral density reduced mechanical strength in mdx and dko mice. The findings reveal that muscle activity can regulate bone mass, structure, mineral accrual, and strength, especially in the context of dystrophin and/or utrophin deficiency. The results provide unique insights into the development of bone fragility in DMD and for devising interventions to improve musculoskeletal health.NEW & NOTEWORTHY Patients with Duchenne muscular dystrophy (DMD) develop bone fragility because of muscle weakness and immobilization. We investigated whether increasing muscle contractile activity through low-frequency stimulation (LFS) could alter bone architecture in dystrophin-deficient (mdx) or dystrophin- and utrophin-deficient (dko) mouse models of DMD. Chronic LFS reduced tibial diaphysis cross sections in mdx and dko mice, without affecting bone shape in healthy mice. LFS affected the distribution of bone mineral density across all phenotypes, with the magnitude of effect being dependent on disease severity.


Assuntos
Distrofina , Distrofia Muscular de Duchenne , Animais , Camundongos , Camundongos Endogâmicos mdx , Utrofina/genética , Camundongos Endogâmicos C57BL , Músculo Esquelético , Debilidade Muscular , Modelos Animais de Doenças
14.
Plant J ; 115(4): 926-936, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37147901

RESUMO

Diatoms are photosynthetic unicellular microalgae that drive global ecological phenomena in the biosphere and are emerging as sustainable feedstock for an increasing number of industrial applications. Diatoms exhibit enormous taxonomic and genetic diversity, which often results in peculiar biochemical and biological traits. Transposable elements (TEs) represent a substantial portion of diatom genomes and have been hypothesized to exert a relevant role in enriching genetic diversity and making a core contribution to genome evolution. Here, through long-read whole-genome sequencing, we identified a mutator-like element (MULE) in the model diatom Phaeodactylum tricornutum, and we report the direct observation of its mobilization within the course of a single laboratory experiment. Under selective conditions, this TE inactivated the uridine monophosphate synthase (UMPS) gene of P. tricornutum, one of the few endogenous genetic loci currently targeted for selectable auxotrophy for functional genetics and genome-editing applications. We report the observation of a recently mobilized transposon in diatoms with unique features. These include the combined presence of a MULE transposase with zinc-finger SWIM-type domains and a diatom-specific E3 ubiquitin ligase of the zinc-finger UBR type, which are suggestive of a mobilization mechanism. Our findings provide new elements for the understanding of the role of TEs in diatom genome evolution and in the enrichment of intraspecific genetic variability.


Assuntos
Diatomáceas , Animais , Diatomáceas/genética , Diatomáceas/metabolismo , Genoma , Uridina Monofosfato/metabolismo , Equidae/genética , Zinco/metabolismo
15.
Surgery ; 174(2): 203-208, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37188583

RESUMO

BACKGROUND: The COVID-19 pandemic severely impacted post-hospitalization care facilities in the United States and hindered their ability to accept new patients for various reasons. This study aimed to assess the impact of the pandemic on discharge disposition after colon surgery and associated postoperative outcomes. METHODS: A retrospective cohort study was performed using the National Surgical Quality Improvement Participant Use File and targeted colectomy. Patients were divided into the following 2 cohorts: (1) pre-pandemic (2017-2019) and (2) pandemic (2020). The primary outcomes included discharge disposition-post-hospitalization facility versus home. The secondary outcomes were rates of 30-day readmissions and other postoperative outcomes. The multivariable analysis assessed for confounders and effect modification on discharge to home. RESULTS: Discharge to posthospitalization facilities decreased by 30% in 2020 compared to 2017 to 2019 (7% vs 10%, P < .001). This occurred despite an increase in emergency cases (15% vs 13%, P < .001) and open surgical approach (32% vs 31%, P < .001) in 2020. Multivariable analysis revealed that patients in 2020 had 38% lower odds of going to post-hospitalization facilities (odds ratio 0.62, P < .001) after adjusting for surgical indications and underlying comorbidities. This decrease in patients going to a post-hospitalization facility was not associated with an increased length of stay or an increase in 30-day readmissions or postoperative complications. CONCLUSION: During the pandemic, patients undergoing colonic resection were less likely to be discharged to a post-hospitalization facility. This shift was not associated with an increase in 30-day complications. This should prompt further research to assess the reproducibility of these associations, especially in a setting without a global pandemic.


Assuntos
COVID-19 , Melhoria de Qualidade , Humanos , Estados Unidos/epidemiologia , Estudos Retrospectivos , Pandemias , Reprodutibilidade dos Testes , COVID-19/epidemiologia , COVID-19/complicações , Colectomia/efeitos adversos , Colo/cirurgia , Alta do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Readmissão do Paciente
16.
Neurol Clin Pract ; 13(2): e200148, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37064589

RESUMO

Background and Objectives: In response to the COVID-19 pandemic, outpatient stroke care delivery was rapidly transformed to outpatient evaluation through video (VTM) and telephone (TPH) telemedicine (TM) visits around the world. We sought to evaluate the sociodemographic differences in outpatient TM use among stroke patients. Methods: We conducted a retrospective chart review of outpatients evaluated at 3 tertiary stroke centers in the early period of the pandemic, 3/16/2020 through 7/31/2020. We compared the use of TM by patient characteristics including age, sex, race/ethnicity, insurance status, stroke type, patient type, and site. The association between TM use and patient characteristics was measured using the relative risk (RR) from a modified Poisson regression, and site-specific effects were controlled using a multilevel analysis. Results: A total of 2,024 visits were included from UTHealth (n = 878), MedStar Health (n = 269), and Columbia (n = 877). The median age was 64 [IQR 52-74] years, and 53% were female. Approximately half of the patients had private insurance, 36% had Medicare, and 15% had Medicaid. Two-thirds of the visits were established patients. TM accounted for 90% of total visits, and the use of TM over office visits was primarily associated with site, not patient characteristics. TM utilization was associated with Asian and other/unknown race. Among TM users, older age, Black race, Hispanic ethnicity, and Medicaid insurance were associated with lower VTM use. Black (aRR 0.88, 95% CI 0.86-0.91, p < 0.001) and Hispanic patients (aRR 0.92, 95% CI 0.87-0.98, p = 0.005) had approximately 10% lower VTM use, while Asian patients (aRR 0.98, 95% CI 0.89-1.07, p = 0.59) had similar VTM use compared with White patients. Patients with Medicaid were less likely to use VTM compared with those with private insurance (aRR 0.86, 95% CI 0.81-0.91, p < 0.001). Discussion: In our diverse cohort across 3 centers, we found differences in TM visit type by race and insurance early during the COVID-19 pandemic. These findings suggest disparities in VTM access across different stroke populations. As VTM remains an integral part of outpatient neurology practice, steps to ensure equitable access are essential.

17.
J Surg Oncol ; 128(1): 58-65, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36939016

RESUMO

BACKGROUND AND OBJECTIVES: In patients with colon cancer with synchronous liver metastasis, treatment algorithms are complex and often require multidisciplinary evaluation. Neoadjuvant therapy is frequently utilized, but there is an unclear relationship with postoperative outcomes in patients with simultaneous resection. METHODS: This is a retrospective cohort study from the National Surgical Quality Improvement Program and Targeted Colectomy databases. All patients with stage IV colon cancer undergoing simultaneous colectomy with synchronous liver metastasis resection or ablation between 2015 and 2019 were identified and categorized into subgroups based on receipt of neoadjuvant chemotherapy. Multivariable logistic regression was utilized to assess for risk factors of anastomotic leaks and serious postoperative complications. RESULTS: We identified 1006 patients who underwent simultaneous colectomy and liver operations. Of those, 418 (41.6%) received neoadjuvant chemotherapy within 90 days of surgery, while 588 (58.4%) had simultaneous upfront surgery. On multivariable logistic regression, neoadjuvant therapy was not associated with postoperative anastomotic leaks (odds ratio [OR]: 1.30; p = 0.39) or serious complications (OR: 1.04; p = 0.82). CONCLUSION: Neoadjuvant therapy does not increase postoperative complications in simultaneous colon and liver resections. These results may alleviate concerns regarding postoperative morbidity in the decision-making process of administering neoadjuvant therapy.


Assuntos
Neoplasias do Colo , Neoplasias Hepáticas , Humanos , Fístula Anastomótica/etiologia , Terapia Neoadjuvante/efeitos adversos , Estudos Retrospectivos , Colectomia/efeitos adversos , Colectomia/métodos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia
18.
Artigo em Inglês | MEDLINE | ID: mdl-36982058

RESUMO

The current study used a family resilience approach to investigate why some offspring of sexual minority parents thrive despite homophobic stigmatization while others do not. Specifically, the study explored the role of two specific family functioning mechanisms (i.e., during adolescence, disclosure of offspring's personal life to their parents, and family compatibility) in the association between experienced homophobic stigmatization at age 17 and subjective well-being at age 25, among 71 offspring (37 females and 34 males, all cisgender) of the National Longitudinal Lesbian Family Study (NLLFS). The results showed that, overall, the offspring reported healthy subjective well-being as emerging adults. However, among NLLFS offspring with less family compatibility as adolescents, homophobic stigmatization was related to higher scores on negative affect when they were emerging adults. Psychological counseling that supports adolescent-parent communication may help prevent the negative effect of homophobic stigmatization on the subjective well-being of offspring with sexual minority parents.


Assuntos
Homossexualidade Feminina , Resiliência Psicológica , Minorias Sexuais e de Gênero , Masculino , Feminino , Adulto , Adolescente , Humanos , Saúde da Família , Homossexualidade Feminina/psicologia , Estereotipagem
19.
Artigo em Inglês | MEDLINE | ID: mdl-36727094

RESUMO

This series of four cases describes unusual intrauterine device (IUD) migration complications, associated etiologic factors, and their management. Recent increases in sociopolitical and medical forces worldwide contributed to inattention to these patients with subclinical IUD complications. The international movement of patients, delays in gynecologic care due to the COVID-19 pandemic, lack of health care access, shifts away from annual examinations, and patients' lack of medical records or IUD awareness can lead to long durations of neglected IUDs and associated complications. These complications might have been avoided or minimized with regular gynecologic health care. Physicians should consider moving toward routine examinations of all IUD patients, rather than away from annual examinations as has been promulgated by some medical societies. Patient education is needed on the importance of routine monitoring of IUDs and retention of device records. Clinicians should become familiar with IUDs from around the world as well as devices no longer being prescribed, as their appearance, associated complications, and presentations may differ from locally currently available devices.

20.
Intern Med J ; 53(5): 787-797, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35717668

RESUMO

BACKGROUND: Aboriginal and Torres Strait Islander people have higher rates of diabetes and its complications than non-Aboriginal people. Rumbalara Aboriginal Co-operative is the major primary healthcare provider for Aboriginal people in the Greater Shepparton region. AIMS: To evaluate the baseline metabolic parameters and presence of diabetes complications in people with type 2 diabetes attending Rumbalara Aboriginal Co-operative in 2017 and compare it with other Aboriginal and Torres Strait Islander studies and Australian specialist diabetes services. METHODS: Clinical and biochemical characteristics, including diabetes type, age, weight, body mass index (BMI), blood pressure, micro- and macrovascular complications, glycosylated haemoglobin (HbA1c), haemoglobin, renal function, lipid profile, urine albumin:creatinine ratio, diabetes medications, renin angiotensin system inhibition therapies, HMG-CoA reductase inhibitors and antiplatelet agents, were determined. RESULTS: One hundred and twenty-six individuals had diabetes, 121 had type 2 diabetes. One hundred and thirteen identified as Aboriginal and/or Torres Strait Islander. Median age was 57.5 (48-68) years, median HbA1c was 7.8% (6.8-9.6) and median BMI was 33.4 kg/m2 (29-42.3). Compared with other Australian Aboriginal and Torres Strait Islander populations, this population was older and had more obesity, but with better glycaemia management. Compared with specialist diabetes services, this population was of similar age, with greater BMI but comparable HbA1c. CONCLUSIONS: Aboriginal people living with type 2 diabetes attending this regional Aboriginal health service have comparable glycaemic management to specialist diabetes services in Australia, managed largely by primary care physicians with limited access to specialist care for the past 5 years.


Assuntos
Diabetes Mellitus Tipo 2 , Serviços de Saúde do Indígena , Humanos , Pessoa de Meia-Idade , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobinas Glicadas , Vitória
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