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1.
Nature ; 620(7975): 855-862, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532930

RESUMO

Patients from historically under-represented racial and ethnic groups are enrolled in cancer clinical trials at disproportionately low rates in the USA1-3. As these patients often have limited English proficiency4-7, we hypothesized that one barrier to their inclusion is the cost to investigators of translating consent documents. To test this hypothesis, we evaluated more than 12,000 consent events at a large cancer centre and assessed whether patients requiring translated consent documents would sign consent documents less frequently in studies lacking industry sponsorship (for which the principal investigator pays the translation costs) than for industry-sponsored studies (for which the translation costs are covered by the sponsor). Here we show that the proportion of consent events for patients with limited English proficiency in studies not sponsored by industry was approximately half of that seen in industry-sponsored studies. We also show that among those signing consent documents, the proportion of consent documents translated into the patient's primary language in studies without industry sponsorship was approximately half of that seen in industry-sponsored studies. The results suggest that the cost of consent document translation in trials not sponsored by industry could be a potentially modifiable barrier to the inclusion of patients with limited English proficiency.


Assuntos
Ensaios Clínicos como Assunto , Barreiras de Comunicação , Termos de Consentimento , Indústria Farmacêutica , Pesquisadores , Traduções , Humanos , Termos de Consentimento/economia , Tradução , Ensaios Clínicos como Assunto/economia , Indústria Farmacêutica/economia , Pesquisadores/economia
2.
Nucleic Acids Res ; 51(3): 1277-1296, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36625255

RESUMO

Microfold (M) cells reside in the intestinal epithelium of Peyer's patches (PP). Their unique ability to take up and transport antigens from the intestinal lumen to the underlying lymphoid tissue is key in the regulation of the gut-associated immune response. Here, we applied a multi-omics approach to investigate the molecular mechanisms that drive M cell differentiation in mouse small intestinal organoids. We generated a comprehensive profile of chromatin accessibility changes and transcription factor dynamics during in vitro M cell differentiation, allowing us to uncover numerous cell type-specific regulatory elements and associated transcription factors. By using single-cell RNA sequencing, we identified an enterocyte and M cell precursor population. We used our newly developed computational tool SCEPIA to link precursor cell-specific gene expression to transcription factor motif activity in cis-regulatory elements, uncovering high expression of and motif activity for the transcription factor ONECUT2. Subsequent in vitro and in vivo perturbation experiments revealed that ONECUT2 acts downstream of the RANK/RANKL signalling axis to support enterocyte differentiation, thereby restricting M cell lineage specification. This study sheds new light on the mechanism regulating cell fate balance in the PP, and it provides a powerful blueprint for investigation of cell fate switches in the intestinal epithelium.


Assuntos
Enterócitos , Células M , Animais , Camundongos , Diferenciação Celular , Mucosa Intestinal , Intestino Delgado , Multiômica , Fatores de Transcrição/metabolismo
3.
Ann Intern Med ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39312777

RESUMO

BACKGROUND: Use of a gestational ("surrogate") carrier is increasingly common. Risk for maternal and neonatal adversity is largely unknown in this birthing population. OBJECTIVE: To determine the risk for severe maternal morbidity (SMM) and severe neonatal morbidity (SNM) in gestational carriers. DESIGN: Population-based cohort study. SETTING: All of Ontario, Canada. PARTICIPANTS: All singleton births at more than 20 weeks' gestation, from 2012 to 2021. MEASUREMENTS: Exposure was type of conception, namely, gestational carriage (main exposure), unassisted conception (comparison group 1), and in vitro fertilization (IVF) (comparison group 2). Main composite outcomes were SMM and SNM. Modified Poisson regression models generated weighted relative risks (wRRs) using propensity score-based overlap weighting. Secondary outcomes included hypertensive disorders of pregnancy, cesarean delivery, preterm birth, and postpartum hemorrhage. RESULTS: Of all eligible singleton births, 846 124 (97.6%) were by unassisted conception, 16 087 (1.8%) by IVF, and 806 (0.1%) by gestational carriage. Respective risks for SMM were 2.3%, 4.3%, and 7.8%. The wRRs were 3.30 (95% CI, 2.59 to 4.20) comparing gestational carriage with unassisted conception and 1.86 (CI, 1.36 to 2.55) comparing gestational carriage with IVF. Respective risks for SNM were 5.9%, 8.9%, and 6.6%, generating wRRs of 1.20 (CI, 0.92 to 1.55) for gestational carriage versus unassisted conception and 0.81 (CI, 0.61 to 1.08) for gestational carriage versus IVF. Hypertensive disorders, postpartum hemorrhage, and preterm birth at less than 37 weeks were also significantly higher contrasting gestational carriers to either comparison group. LIMITATION: Absence of information about indications for choosing a gestational carrier, and oocyte or sperm donor source. CONCLUSION: Among singleton births of more than 20 weeks' gestation, a higher risk for SMM and adverse pregnancy outcomes was seen among gestational carriers compared with women who conceived with and without assistance. Although gestational carriage was associated with preterm birth, there was less clear evidence of severe neonatal morbidity. Potential mechanisms for higher maternal morbidity among gestational carriers require elucidation, alongside developing special care plans for gestational carriers. PRIMARY FUNDING SOURCE: The Canadian Institutes of Health Research.

4.
Cell Physiol Biochem ; 58(4): 393-403, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39166656

RESUMO

BACKGROUND/AIMS: Due to rapid metabolic and growth rates during the first two years of life, the nutritional needs of young children are high. Given the small portion sizes consumed by children between the ages of 6 and 24 months, it is necessary to improve diets to meet the nutritional needs of this age group. Therefore, the analysis of lysine content is an important parameter in the evaluation of enriched foods. METHODS: The utilization of an enzymatic sensor employing lysine-α-oxidase (LOx) as a biorecognition element represents an alternative to the existing methods. This sensor was optimized for quantifying the lysine content in flour mixtures: Quinoa-Lablab purpureus rye - Lablab purpureus, and pole beans - Lablab purpureus, with a maximum ratio of 85g/100g. RESULTS: The addition of lablab purpureus significantly increased the lysine concentration in the enriched samples. When 30 percent was substituted in quinoa, it reached a 143 percent increase. And when 15 percent was substituted in the rye flour, the final concentration of this amino acid increased by 64 percent. In order to quantify the lysine concentration, it was necessary to optimize various parameters during the use of the sensor, e.g. a potentiometric signal was detected upon the depletion of oxygen present during the oxidation of lysine in the samples, and the sensor response was recorded at 2 s. This was possible due to the modification of the pH and the thickness of the membrane. The oxidation of lysine is catalyzed by LOx using molecular oxygen as the electron acceptor. The corresponding acidic compounds and hydrogen peroxide were formed in the reaction medium. CONCLUSION: It was possible to increase and verify the concentration of lysine in all the flours tested through the use of the biosensor, which turned out to be a valid method for controlling the nutritional quality of flours.


Assuntos
Técnicas Biossensoriais , Farinha , Lisina , Farinha/análise , Técnicas Biossensoriais/métodos , Lisina/análise , Lisina/metabolismo , Lisina/química , Alimentos Fortificados/análise , Secale/química , Secale/metabolismo , Chenopodium quinoa/química , Chenopodium quinoa/metabolismo , Aminoácido Oxirredutases/metabolismo
5.
Am J Obstet Gynecol ; 230(6): 649.e1-649.e19, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38307469

RESUMO

BACKGROUND: Endometriosis is a chronic gynecologic disorder that leads to considerable pain and a reduced quality of life. Although its physiological manifestations have been explored, its impact on mental health is less well defined. Existing studies of endometriosis and mental health were conducted within diverse healthcare landscapes with varying access to care and with a primary focus on surgically diagnosed endometriosis. A single-payer healthcare system offers a unique environment to investigate this association with fewer barriers to access care while considering the mode of endometriosis diagnosis. OBJECTIVE: Our objective was to assess the association between endometriosis and the risk for mental health conditions and to evaluate differences between patients diagnosed medically and those diagnosed surgically. STUDY DESIGN: A matched, population-based retrospective cohort study was conducted in Ontario and included patients aged 18 to 50 years with a first-time endometriosis diagnosis between January 1, 2010, and July 1, 2020. Endometriosis exposure was determined through either medical or surgical diagnostic criteria. A medical diagnosis was defined by the use of the corresponding International Classification of Disease diagnostic codes from outpatient and in-hospital visits, whereas a surgical diagnosis was identified through inpatient or same-day surgeries. Individuals with endometriosis were matched 1:2 on age, sex, and geography to unexposed individuals without a history of endometriosis. The primary outcome was the first occurrence of any mental health condition after an endometriosis diagnosis. Individuals with a mental health diagnosis in the 2 years before study entry were excluded. Cox regression models were used to generate hazard ratios with adjustment for hysterectomy, salpingo-oophorectomy, infertility, pregnancy history, qualifying surgery for study inclusion, immigration status, history of asthma, abnormal uterine bleeding, diabetes, fibroids, hypertension, irritable bowel disorder, migraines, and nulliparity. RESULTS: A total of 107,832 individuals were included, 35,944 with a diagnosis of endometriosis (29.5% medically diagnosed, 60.5% surgically diagnosed, and 10.0% medically diagnosed with surgical confirmation) and 71,888 unexposed individuals. Over the study period, the incidence rate was 105.3 mental health events per 1000 person-years in the endometriosis group and 66.5 mental health events per 1000 person-year among unexposed individuals. Relative to the unexposed individuals, the adjusted hazard ratio for a mental health diagnosis was 1.28 (95% confidence interval, 1.24-1.33) among patients with medically diagnosed endometriosis, 1.33 (95% confidence interval, 1.16-1.52) among surgically diagnosed patients, and 1.36 (95% confidence interval, 1.2-1.6) among those diagnosed medically with subsequent surgical confirmation. The risk for receiving a mental health diagnosis was highest in the first year after an endometriosis diagnosis and declined in subsequent years. The cumulative incidence of a severe mental health condition requiring hospital visits was 7.0% among patients with endometriosis and 4.6% among unexposed individuals (hazard ratio, 1.56; 95% confidence interval, 1.53-1.59). CONCLUSION: Endometriosis, regardless of mode of diagnosis, is associated with a marginally increased risk for mental health conditions. The elevated risk, particularly evident in the years immediately following the diagnosis, underscores the need for proactive mental health screening among those newly diagnosed with endometriosis. Future research should investigate the potential benefits of mental health interventions for people with endometriosis with the aim of enhancing their overall quality of life.


Assuntos
Endometriose , Humanos , Feminino , Endometriose/epidemiologia , Endometriose/cirurgia , Endometriose/psicologia , Endometriose/complicações , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto Jovem , Ontário/epidemiologia , Transtornos Mentais/epidemiologia , Adolescente , Estudos de Coortes , Saúde Mental , Modelos de Riscos Proporcionais
6.
Pediatr Blood Cancer ; : e31321, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238140

RESUMO

BACKGROUND: Increasing representation in clinical trials is a priority for the National Cancer Institute and Children's Oncology Group (COG). Our survey of COG-affiliated institutions revealed that many sites have insufficient processes and resources to enroll children whose parents use languages other than English (LOE). We describe reported barriers and facilitators to enrolling children in clinical trials when parents use LOE and propose opportunities for improvement. PROCEDURES: We sent a 20-item survey to COG-affiliated institutions. Five items allowed respondents to expand on replies to questions about (a) local institutional review board (IRB) requirements regarding translation of consent documents, (b) contributors to provider discomfort consenting parents who use LOE, (c) available language services and resources, and (d) barriers to enrolling children whose parents use LOE or offer ideas about approaches to improvements. Two pairs of researchers independently coded free-text responses and compared results for concordance. RESULTS: A total of 139 (N = 230; 60%) institutions returned the survey. Respondents were mainly physician principal investigators (n = 79/139; 57%) at the United States sites (n = 118/139; 85%) serving less than 100 newly diagnosed children per year (n = 99/139, 71%). They described challenges at multiple levels. Proposed approaches to improvements included centralized provision of translated materials and video educational materials in various languages, and collaborating with IRBs on regulatory processes that protect families and facilitate equitable clinical trial access. CONCLUSIONS: Clinical trial consortia, such as COG, face challenges in enrolling representative samples. Further research is required to design and implement multilevel interventions to ensure equitable access for all, regardless of language used, and mitigate disparate research participation.

7.
BJOG ; 131(4): 415-422, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37973606

RESUMO

OBJECTIVE: To evaluate the risk of miscarriage following SARS-CoV-2 vaccination, while accounting for the competing risk of induced abortion. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women aged 15-50 years with a confirmed pregnancy at ≤19 completed weeks' gestation. METHODS: Exposure to first SARS-CoV-2 vaccination, handled in a time-varying manner, was defined as (i) unvaccinated, (ii) remotely vaccinated >28 days before the estimated conception date or (iii) recently vaccinated ≤28 days before conception and up to 120 days after conception. MAIN OUTCOME MEASURES: The outcome was miscarriage, occurring between the estimated date of conception and up to 19 completed weeks of pregnancy. Fine-Grey hazard models, accounting for the competing risk of induced abortion, generated hazard ratios (aHR), adjusted for socio-demographic factors, comorbidities, and biweekly periods. RESULTS: Included were 246 259 pregnant women, of whom 34% received a first SARS-CoV-2 vaccination. Miscarriage occurred at a rate of 3.6 per 10 000 person-days among remotely vaccinated women and 3.2 per 10 000 person-days among those recently vaccinated, in contrast to a rate of 1.9 per 10 000 person-days among unvaccinated women, with corresponding aHR of 0.98 (95% confidence interval [CI] 0.91-1.07) and 1.00 (95% CI 0.93-1.08). CONCLUSIONS: SARS-CoV-2 vaccination was not associated with miscarriage while accounting for the competing risk of induced abortion. This study reiterates the importance of including pregnant women in new vaccine clinical trials and registries, and the rapid dissemination of vaccine safety data.


Assuntos
Aborto Espontâneo , Vacinas contra COVID-19 , COVID-19 , Feminino , Humanos , Gravidez , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Estudos de Coortes , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Ontário/epidemiologia , SARS-CoV-2 , Vacinação/efeitos adversos
8.
BJOG ; 131(5): 589-597, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38239019

RESUMO

OBJECTIVE: To study the association between maternal exposure to arsenic, cadmium, lead, manganese and mercury, time-to-pregnancy (TTP) and infertility. DESIGN: Pregnancy-based retrospective TTP cohort study. SETTING: Hospitals and clinics from ten cities across Canada. POPULATION: A total of 1784 pregnant women. METHODS: Concentrations of arsenic, cadmium, lead, manganese and mercury were measured in maternal whole blood during the first trimester of pregnancy as a proxy of preconception exposure. Discrete-time Cox proportional hazards models generated fecundability odds ratios (FOR) for the association between metals and TTP. Logistic regression generated odds ratios (OR) for the association between metals and infertility. Models were adjusted for maternal age, pre-pregnancy body mass index, education, income, recruitment site and plasma lipids. MAIN OUTCOME MEASURES: TTP was self-reported as the number of months of unprotected intercourse to become pregnant. Infertility was defined as TTP longer than 12 months. RESULTS: A total of 1784 women were eligible for the analysis. Mean ± SD maternal age and gestational age at interview were 32.2 ± 5.0 years, and 11.6 ± 1.6 weeks, respectively. Exposure to arsenic, cadmium, manganese or mercury was not associated with TTP or infertility. Increments of one standard deviation of lead concentrations resulted in a shorter TTP (adjusted FOR 1.09, 95% CI 1.02-1.16); however, the association was not linear when exposure was modelled in tertiles. CONCLUSION: Blood concentrations of metals at typical levels of exposure among Canadian pregnant women were not associated with TTP or infertility. Further studies are needed to assess the role of lead, if any, on TTP.


Assuntos
Arsênio , Infertilidade , Mercúrio , Feminino , Gravidez , Humanos , Exposição Materna , Estudos de Coortes , Manganês , Chumbo , Tempo para Engravidar , Cádmio/efeitos adversos , Estudos Retrospectivos , Canadá
9.
BMC Womens Health ; 24(1): 280, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720297

RESUMO

BACKGROUND: Infertility is a marginalized sexual and reproductive health issue in low-resource settings. Globally, millions are affected by infertility, but the lack of a universal definition makes it difficult to estimate the prevalence of infertility at the population level. Estimating the prevalence of infertility may inform targeted and accessible intervention, especially for a resource-limited country like Ethiopia. This study aims to estimate the prevalence of female infertility in Ethiopia using the Demographic and Health Survey (DHS) through two approaches: (i) the demographic approach and (ii) the current duration approach. METHODS: Data from 15,683 women were obtained through the 2016 Ethiopian DHS. The demographic approach estimates infertility among women who had been married/in a union for at least five years, had never used contraceptives, and had a fertility desire. The current duration approach includes women at risk of pregnancy at the time of the survey and determines their current length of time-at-risk of pregnancy at 12, 24, and 36 months. Logistic regression analysis estimated the prevalence of infertility and factors associated using the demographic approach. Parametric survival analysis estimated the prevalence of infertility using the current duration approach. All estimates used sampling weights to account for the DHS sampling design. STATA 14 and R were used to perform the statistical analysis. RESULTS: Using the demographic definition, the prevalence of infertility was 7.6% (95% CI 6.6-8.8). When stratified as primary and secondary infertility, the prevalence was 1.4% (95% CI 1.0-1.9) and 8.7% (95% CI 7.5-10.1), respectively. Using the current duration approach definition, the prevalence of overall infertility was 24.1% (95% CI 18.8-34.0) at 12-months, 13.4% (95% CI 10.1-18.6) at 24-months, and 8.8% (95% CI 6.5-12.3) at 36-months. CONCLUSION: The demographic definition of infertility resulted in a lower estimate of infertility. The current duration approach definition could be more appropriate for the early detection and management of infertility in Ethiopia. The findings also highlight the need for a comprehensive definition of and emphasis on infertility. Future population-based surveys should incorporate direct questions related to infertility to facilitate epidemiological surveillance.


Assuntos
Infertilidade Feminina , Humanos , Etiópia/epidemiologia , Feminino , Adulto , Prevalência , Infertilidade Feminina/epidemiologia , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Inquéritos Epidemiológicos , Gravidez
10.
Curr Microbiol ; 81(11): 361, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287836

RESUMO

A great number of free radicals have a negative impact on the human body, and an increased interest in the identification of new natural molecules with antioxidant properties has emerged due to concerns about synthetic antioxidants. Here, the antioxidant effect of four exo-polysaccharides (EPS) extracts obtained from submerged cultivation of Nothophellinus andinopatagonicus and Pseudoinonotus crustosus (N and P, respectively) in two culture media (M1 and M2) at 2 concentrations (100 and 250 µg/ml) was studied; then, its relation with the chemical composition of the EPS was evaluated. To assess the antioxidant activities of the extracts, several in vitro assays were performed: DPPH and ABTS radical scavenging, ferric-reducing antioxidant power, chelating ability on ferrous ions, and inhibition of the lipid peroxidation. The concentrations tested here were much lower than those reported in previous works. Despite variations in chemical composition and monosaccharide profiles among the extracts, all demonstrated antioxidant activity, although the type of activity differed; only P-M1 exhibited a good antioxidant activity across all assays. This extract contained the highest proportion of phenolic compounds, and also displayed the highest radical scavenging activity. Although the utilization of polysaccharides as functional food ingredients remains limited, we propose P-M1 as a promising candidate for a nutraceutical product. Additionally, a formulation could be made with a combination of extracts to create an antioxidant-rich supplement. Additional research is needed to confirm our findings in a cellular environment and to elucidate the mechanisms that drive their antioxidant activities, ultimately facilitating their development and utilization as nutraceutical products.


Assuntos
Antioxidantes , Antioxidantes/farmacologia , Antioxidantes/química , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Argentina , Polissacarídeos/farmacologia , Polissacarídeos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Fenóis/farmacologia , Fenóis/química , Hypocreales/química , Hypocreales/metabolismo , Benzotiazóis/metabolismo
11.
J Obstet Gynaecol Can ; 46(2): 102238, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37827332

RESUMO

This population-based cohort study in Ontario, Canada evaluated the association between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus, and the mediating effect of obesity. The study included 1 268 901 pregnancies between 2006 and 2018; 387 748 with maternal PCOS and 881 153 without PCOS. Modified Poisson regression generated relative risks adjusted for maternal covariates. Causal mediation analyses accounted for the indirect effect of obesity. Relative to individuals without PCOS, those with PCOS had a slightly higher rate (6.0% vs. 4.9%) and adjusted relative risk (1.05; 95% CI 1.03-1.06) of gestational diabetes mellitus. Obesity mediated a significant proportion (90%) of this association. Preconception counselling and future research should include strategies to support weight optimization in patients with PCOS.


Assuntos
Diabetes Gestacional , Síndrome do Ovário Policístico , Gravidez , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Estudos de Coortes , Obesidade/complicações , Obesidade/epidemiologia , Ontário/epidemiologia
12.
J Obstet Gynaecol Can ; 46(10): 102638, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39154661

RESUMO

OBJECTIVES: To evaluate the association between adolescent and young adult (AYA) breast cancer (BC) and the adverse pregnancy outcomes of preterm birth, small for gestational age birth, cesarean delivery, and preeclampsia, and the effect of fertility treatment on this association. METHODS: Population-based cohort study with universal coverage health data for Ontario, Canada. BC was identified from the Ontario Cancer Registry. All births >220 weeks gestation between April 2006 to March 2018 were included. Modified Poisson regression generated risk ratios between AYA BC and adverse pregnancy outcomes, adjusted for maternal characteristics. Models were stratified by fertility treatment. RESULTS: Among 1 189 980 deliveries, 474 mothers had AYA BC history (exposed), while 1 189 506 had no cancer history (unexposed). AYA BC was associated with cesarean delivery (adjusted risk ratio [aRR] 1.26; 95% CI 1.14-1.39). There was no association between AYA BC and other adverse outcomes. Modelling cesarean delivery subtypes, AYA BC was associated with increased risk of planned (aRR 1.27; 95% CI 1.08-1.49) and unplanned cesarean delivery (aRR 1.41; 95% CI 1.20-1.66). An increased risk of cesarean delivery in exposed persisted among singleton pregnancies (aRR 1.27; 95% CI 1.15-1.41), but not in models stratified by mode of conception (fertility treatment: aRR 1.07; 95% CI 0.84-1.36; unassisted conception: aRR 1.30; 95% CI 1.16-1.46). CONCLUSIONS: A history of AYA BC did not confer an elevated risk of adverse pregnancy outcomes, except for planned and unplanned cesarean delivery. The risk of adverse pregnancy outcomes does not appear to be an indication for delayed pregnancy after AYA BC diagnosis.

13.
J Obstet Gynaecol Can ; 46(8): 102582, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38866202

RESUMO

This population-based cohort evaluated the association between endometriosis and severe maternal morbidity (SMM), and the mediating effect of infertility and fertility treatment. Included were all singleton deliveries in Ontario between 2006 and 2014. Modified Poisson regression generated adjusted relative risks. Mediation analysis estimated the direct effect of endometriosis and indirect effect through infertility and mode of conception. 787 449 deliveries were included (19 099, 2.4% with endometriosis). SMM occurred in 29.0 per 1000 deliveries among women with endometriosis, in contrast to 18.2 per 1000 deliveries among those without endometriosis-corresponding to an adjusted relative risk of SMM of 1.43 (95% CI 1.31-1.56). Mediation analysis demonstrated that the effect of endometriosis on SMM was independent of infertility or fertility treatment. We conclude that SMM in women with endometriosis appears to be due to the disease itself and not to infertility or related treatments.


Assuntos
Endometriose , Infertilidade Feminina , Humanos , Feminino , Endometriose/complicações , Endometriose/epidemiologia , Adulto , Ontário/epidemiologia , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/etiologia , Gravidez , Estudos de Coortes , Complicações na Gravidez/epidemiologia
14.
Ann Hum Biol ; 51(1): 2390829, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39206847

RESUMO

CONTEXT: Robust associations have been identified between fertility during adolescence and the disablement process, including pathologies, impairments, functional limitations and disability. Limited theoretical or empirical research considers how and why such relationships exist generally or with the individual associated components of disablement. OBJECTIVE: To consolidate and critically evaluate literature to describe testable, theory-based hypotheses to guide future research on the mechanisms by which fertility during adolescence contributes to disablement. METHODS: Targeted literature review of research from diverse global settings contextualised in two well-accepted theoretical frameworks in life-course epidemiology: the cumulative risk model and the critical period approach. RESULTS: Five hypothesised causal pathways linking adolescent fertility to disablement in later life are described: 1) Causal relationship initiated by fertility during adolescence; 2) Common cause(s) for both, such as adverse childhood experiences; 3) Contributing cause(s) to adolescent fertility; 4) Interaction between adolescent fertility and other risk factors; and 5) Critical period effects unique to adolescence. Most research on the topic is on pathologies versus functional limitations and disability. CONCLUSION: We highlight promising research avenues to inform future research and interventions on adolescent fertility and the disablement process. This work provides theoretical clarity, identifies research gaps, and offers hypotheses-testing opportunities for future research.


Assuntos
Pessoas com Deficiência , Fertilidade , Humanos , Adolescente , Pessoas com Deficiência/estatística & dados numéricos , Feminino , Fatores de Risco , Lacunas de Evidências
15.
Int J Mol Sci ; 25(18)2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39337414

RESUMO

The maritime pine (Pinus pinaster Ait.) is a highly valuable Mediterranean conifer. However, recurrent drought events threaten its propagation and conservation. P. pinaster populations exhibit remarkable differences in drought tolerance. To explore these differences, we analyzed stem transcriptional profiles of grafts combining genotypes with contrasting drought responses under well-watered and water-stress regimes. Our analysis underscored that P. pinaster drought tolerance is mainly associated with constitutively expressed genes, which vary based on genotype provenance. However, we identified key genes encoding proteins involved in water stress response, abscisic acid signaling, and growth control including a PHD chromatin regulator, a histone deubiquitinase, the ABI5-binding protein 3, and transcription factors from Myb-related, DOF NAC and LHY families. Additionally, we identified that drought-tolerant rootstock could enhance the drought tolerance of sensitive scions by regulating the accumulation of transcripts involved in carbon mobilization, osmolyte biosynthesis, flavonoid and terpenoid metabolism, and reactive oxygen species scavenging. These included genes encoding galactinol synthase, CBL-interacting serine/threonine protein kinase 5, BEL1-like homeodomain protein, dihydroflavonol 4-reductase, and 1-deoxy-D-xylulose-5-phosphate. Our results revealed several hub genes that could help us to understand the molecular and physiological response to drought of conifers. Based on all the above, grafting with selected drought-tolerant rootstocks is a promising method for propagating elite recalcitrant conifer species, such as P. pinaster.


Assuntos
Secas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Pinus , Pinus/genética , Pinus/fisiologia , Pinus/metabolismo , Perfilação da Expressão Gênica/métodos , Transcriptoma , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Caules de Planta/genética , Caules de Planta/metabolismo , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resistência à Seca
16.
Rev Argent Microbiol ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39277447

RESUMO

Rectal swabs (122) from pediatric patients were analyzed by polymerase chain reaction (PCR) for the detection of EPEC and STEC. STEC isolates were tested for the presence of stx1, stx2, eae, saa and ehxA. All eae-positive samples were tested for the presence of bfpA, and antigen O was determined using the agglutination test. Int1 and Int2 were detected to identify the presence of integrons class 1 and 2, respectively. Escherichia coli was detected in 68% of the samples, of which 18.8% were STEC (2.45%) and EPEC (16.3%). Serogroups STEC O145 and EPEC O130, O113 and O157 were observed, while three strains were non-typable. None of the EPEC strains carrying tbfpA and class 1 and 2 integrons was detected in any of the samples. The results obtained are important considering the virulence profiles found in the isolated EPEC and STEC strains and the serogroups associated with disease in humans.

17.
Pediatr Blood Cancer ; 70 Suppl 6: e30592, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37501542

RESUMO

The Children's Oncology Group (COG) Diversity and Health Disparities Committee's (DHDC's) mission is to guarantee the highest standard of care for children and adolescents and young adults (AYA) with cancer regardless of ethnic, racial, gender, or socioeconomic background. We strive to identify and address issues of disparity within the existing scientific structure of COG and to support research across COG to improve survival by ensuring equitable access to COG-sponsored clinical trials. We are committed to advance COG-led research identifying mechanistic drivers of disparities and, concurrently, evaluating interventions to alleviate disparities in the COG trial setting. As trials identify the most promising therapies, diverse representation is critical to ensure that findings are relevant to everyone. Factors impacting clinical trial participation among vulnerable populations are complex, consisting of barriers at societal, systems, and individual levels. Recent efforts by investigators within DHDC demonstrated that trial-embedded collection of family-reported sociodemographic data and social determinants of health (SDoH) is feasible and acceptable in the context of COG. Diversity in the pediatric oncology workforce is essential and one potential approach to improving representation on clinical trials. To support and retain diverse oncology providers and researchers, a Minority Young Investigator Award (MYIA) was created to facilitate opportunities for graduating trainees and YIs with an interest in childhood cancer disparities research within COG. Although there are challenges to achieve the DHDC's priorities, only through collaboration and support for this work we will be able to elucidate mechanisms underlying inferior survival outcomes for historically marginalized children and AYA, and more importantly, implement interventional investigation to improve outcomes.


Assuntos
Neoplasias , Adolescente , Adulto Jovem , Humanos , Criança , Neoplasias/terapia , Oncologia , Inquéritos e Questionários , Grupos Minoritários , Grupos Raciais
18.
Paediatr Perinat Epidemiol ; 37(8): 719-732, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37921434

RESUMO

BACKGROUND: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. OBJECTIVES: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. POPULATION: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. PRELIMINARY RESULTS: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). CONCLUSIONS: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.


Assuntos
Desenvolvimento Infantil , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Humanos , Gravidez , Lactente , Feminino , Pré-Escolar , Canadá/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Materna/efeitos adversos , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
19.
Scand J Gastroenterol ; 58(4): 435-440, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36254785

RESUMO

BACKGROUND: Endoscopic mucosal resection (EMR) is an effective method for removing non-pedunculated polyps ≥ 20 mm. We aimed to examine changes in EMR techniques over a 9-year period and evaluate frequency of histologic-confirmed recurrence. METHODS: We identified patients who underwent EMR of non-pedunculated polyps ≥ 20 mm at a safety net and the Veteran's Affairs (VA) hospital in Houston, Texas between 2012 and 2020. Odds ratios (ORs) and 95% confidence intervals (CI) for associations with recurrence risk were estimated using multivariable logistic regression. RESULTS: 461 unique patients were included. The histologic-confirmed recurrence was 29.0% at 15.6 months median follow up (IQR 12.3 - 17.4). Polyps removed between 2018 and 2020 had a 0.43 decreased odds of recurrence vs. polyps removed between 2012 and 2014. The use of viscous lifting agents increased over time (from 0 to 54%), and the use of saline was associated with increased risk of recurrence (OR 2.28 [CI 1.33 - 3.31]). CONCLUSIONS: Histologic-confirmed recurrence after EMR for non-pedunculated polyps ≥ 20 mm decreased over the seven year-period. Saline was associated with a higher risk of recurrence and the use of more viscous agents increased over time.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Pólipos do Colo/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Colorretais/cirurgia
20.
J Pediatr Hematol Oncol ; 45(1): e1-e3, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35973025

RESUMO

Complete or partial loss of chromosome 7 is a common and well-known cytogenetic abnormality associated with preleukemic myelodysplasia and myeloid leukemia but not with autoimmune myelofibrosis. Detection of this molecular change represents poor prognosis. When malignant transformation occurs, the condition tends to be chemotherapy-resistant requiring haematopoietic stem cell transplantation (HSCT) to obtain a cure. Disappearance after immunosuppressive therapy has been documented in children with hematological disorders but not in association with cyclophosphamide and systemic lupus erythematous.We present the interesting case of a 12-year-old male with monosomy 7, systemic lupus erythematous, and lupus nephritis with the resolution of the monosomy 7 and autoimmune myelofibrosis after treatment with cyclophosphamide, along with a review of the literature.


Assuntos
Nefrite Lúpica , Mielofibrose Primária , Masculino , Criança , Humanos , Nefrite Lúpica/complicações , Nefrite Lúpica/genética , Mielofibrose Primária/complicações , Mielofibrose Primária/genética , Mielofibrose Primária/terapia , Cromossomos Humanos Par 7/genética , Ciclofosfamida , Imunossupressores
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