Maritime Pine Rootstock Genotype Modulates Gene Expression Associated with Stress Tolerance in Grafted Stems.

Climate change-induced hazards, such as drought, threaten forest resilience, particularly in vulnerable regions such as the Mediterranean Basin. Maritime pine (Pinus pinaster Aiton), a model species in Western Europe, plays a crucial role in the Mediterranean forest due to its genetic diversity and ecological plasticity. This study characterizes transcriptional profiles of scion and rootstock stems of four P. pinaster graft combinations grown under well-watered conditions. Our grafting scheme combined drought-sensitive and drought-tolerant genotypes for scions (GAL1056: drought-sensitive scion; and Oria6: drought-tolerant scion) and rootstocks (R1S: drought-sensitive rootstock; and R18T: drought-tolerant rootstock). Transcriptomic analysis revealed expression patterns shaped by genotype provenance and graft combination. The accumulation of differentially expressed genes (DEGs) encoding proteins, involved in defense mechanisms and pathogen recognition, was higher in drought-sensitive scion stems and also increased when grafted onto drought-sensitive rootstocks. DEGs involved in drought tolerance mechanisms were identified in drought-tolerant genotypes as well as in drought-sensitive scions grafted onto drought-tolerant rootstocks, suggesting their establishment prior to drought. These mechanisms were associated with ABA metabolism and signaling. They were also involved in the activation of the ROS-scavenging pathways, which included the regulation of flavonoid and terpenoid metabolisms. Our results reveal DEGs potentially associated with the conifer response to drought and point out differences in drought tolerance strategies. These findings suggest genetic trade-offs between pine growth and defense, which could be relevant in selecting more drought-tolerant Pinus pinaster trees.

Clinical trial recruitment of people who speak languages other than english: a children's oncology group report.

BACKGROUND: Persons who speak languages other than English (LOE) are underrepresented in clinical trials; this may be due in part to inadequate multilevel resources. We conducted a survey of institutions affiliated with the Children's Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services. METHODS: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak LOE to COG trials. Descriptive statistics were used to summarize responses; responses were compared by institution size, type, and respondent role. RESULTS: The survey was sent to a total of 230 institutions, and the response rate was 60% (n = 139). In total, 60% (n = 83) had access to short form consents. Full consent form translation was required at 50% of institutions, and 12% of Institutional Review Boards restricted use of centrally translated consent forms. Forty-six percent of institutions reported insufficient funding to support translation costs; 15% had access to no-cost translation services. Forty-four percent (n = 61) were required to use in-person interpreters for consent discussions; the most cited barrier to obtaining consent was lack of available in-person interpreters (56%). Forty-six percent (n = 69) reported that recruiting persons who speak LOE to clinical trials was somewhat or very difficult. CONCLUSIONS: Institutions affiliated with COG face resource-specific challenges that impede recruitment of participants who speak LOE in clinical trials. These findings indicate an urgent need to identify strategies aimed at reducing recruitment barriers to ensure equitable access to clinical trials.

Endometriosis, Severe Maternal Morbidity, and the effect of Infertility: Population-Based Cohort Study.

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 (aRRs). Mediation analysis estimated 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 RR 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.

Unicanvas: Exploring a tool for strategic management.

Purpose: This research proposes an adapted version of Business Model Canvas (BMC) as a strategic instrument for Higher Education Institutions (HEIs). University-Model Canvas (Unicanvas) is intended to be a critical visual and dynamic tool for addressing the challenges faced by entrepreneurial universities in their quintuple helix model. Research methods/Approach: Considering the new challenges facing HEIs, transfer knowledge, corporate social responsibility, internationalization, digitalization, sustainability, and the critical role of universities in innovation and regional development, we adapt the strategic building blocks of the BMC in the context of universities. Findings and implications: Departing from BMC, we propose 10 strategic building blocks against the nine BMCs, including an achievement box. The new challenges HEIs face, the expansion of university outputs, and new societal demands highlight the opportunity to use this tool instead of traditional and static strategic planning models to discuss and concretise their differentiated way of competing. The use of this participative, dynamic, intuitive, and flexible strategic tool will facilitate the holistic strategic management of these institutions in their current new challenges.

Universities are responsible for training students, generating knowledge from their research, and transferring it to the market. This triple function is developed in a changing context with significant challenges, such as demographic changes, rapid technological advances, or limited public financing. Changes for Higher Education Institutions (HEIs) imply contemplating key issues such as transfer and innovation, internationalization, digitalization, sustainability, or regional development in their strategic objectives. For this reason, many universities are asking themselves: How can they approach the strategic management of universities to face these challenges? Universities have traditionally approached the management of their institutions based on traditional and static strategic planning models. However, universities with more attractive strategic tools from the business and entrepreneurship fields could design strategies to meet the interests of multiple academic and market stakeholders. The original Business Model Canvas (BMC) is a widely accepted tool for business model innovation. It provides an easy, dynamic, intuitive, and flexible vision that can be continually improved to shape and renew any business strategy. The main goal of this research is to propose a modified version of BMC, named University-Model Canvas (Unicanvas). A Unicanvas is proposed for its effectiveness, practicality, and easy-to-use tool design and development of university strategic management. We aim to help university managers and administrators understand the possibilities of this tool for appropriate strategic management in these changing times.

The varying estimation of infertility in Ethiopia: the need for a comprehensive definition.

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.

Benefits of being part of a support group for caregivers of children with multiple disabilities: a qualitative study. / Beneficios de pertenecer a un grupo de apoyo de cuidadoras de niños con discapacidad múltiple: un estudio cualitativo.

OBJECTIVE: Motivation for the study. Filling a knowledge gap regarding support groups for caregivers of children with multiple disabilities. Main findings. Support groups are valuable spaces for social support and learning for caregivers of children with multiple disabilities. They facilitate resilience and coping strategies following the birth of a child with multiple disabilities. They promote the participation and empowerment of caregivers of children with multiple disabilities to address access barriers and advocate for the fundamental rights of children. Implications. It is important to promote and support support groups for caregivers of children with multiple disabilities. To explore the perceived benefits of participating in a support group of caregivers of children with multiple disabilities. MATERIALS AND METHODS.: A qualitative study with a focused ethnographic approach was conducted from October 2022 to February 2023, in which we applied convenience sampling. We included 20 caregivers of children with multiple disabilities. Information was collected through participant observation, focus groups, and semi-structured interviews. Thematic analysis was performed by applying Braun and Clark's proposals. RESULTS.: The emerging themes were: social support network: integrating, informing, and helping each other; learning space: learning to take care and to take care of oneself; promoting empowerment: identifying and facing access barriers. CONCLUSIONS.: We found that the support group functions as a social support network provides information, reduces uncertainty, and facilitates coping and resilience after the birth and upbringing of a child with multiple disabilities. It is a space where one learns to care for and take care of oneself and where empowerment for the defense of the rights of children with disabilities is promoted.

OBJETIVO.: Motivación para realizar el estudio. Llenar un vacío de conocimiento sobre los grupos de apoyo de cuidadoras de niños con discapacidad múltiple. Principales hallazgos. Los grupos de apoyo son espacios valiosos de apoyo social y aprendizaje para las cuidadoras de niños con discapacidad múltiple. Facilitan la resiliencia, el afrontamiento tras tener un niño con discapacidad múltiple. Favorecen la participación y empoderamiento de las cuidadoras de niños con discapacidad múltiple para enfrentar barreras de acceso y defender los derechos fundamentales de los niños. Implicancias. Es importante fomentar y respaldar los grupos de apoyo para cuidadoras de niños con discapacidad múltiple. Explorar la percepción de los beneficios de participar en un grupo de apoyo de cuidadoras de niños con discapacidad múltiple. MATERIALES Y MÉTODOS.: Estudio cualitativo, enfoque etnográfico focalizado, realizado de octubre del 2022 a febrero del 2023, muestreo por conveniencia, participaron 20 cuidadoras de niños con discapacidad múltiple. La información se recolectó mediante observación participante, grupos de discusión y entrevistas semiestructuradas. Se realizó análisis temático aplicando las propuestas por Braun y Clark. RESULTADOS.: Los temas emergentes fueron: red de apoyo social: integrarse, informarse y ayudarse mutuamente; espacio de aprendizaje: se aprende a cuidar y a cuidarse; promueve el empoderamiento: identificar y enfrentar barreras de acceso. CONCLUSIONES.: El grupo de apoyo funciona como una red de apoyo social, proporciona información, reduce la incertidumbre, facilita el afrontamiento y la resiliencia tras el nacimiento y crianza de un hijo con discapacidad múltiple. Espacio donde se aprende a cuidar y a cuidarse a sí mismo y donde se promueve el empoderamiento para la defensa de los derechos de los niños con discapacidad.

Multifetal Pregnancy After Implementation of a Publicly Funded Fertility Program.

Importance: A publicly funded fertility program was introduced in Ontario, Canada, in 2015 to increase access to fertility treatment. For in vitro fertilization (IVF), the program mandated an elective single-embryo transfer (eSET) policy. However, ovulation induction and intrauterine insemination (OI/IUI)-2 other common forms of fertility treatment-were more difficult to regulate in this manner. Furthermore, prior epidemiologic studies only assessed fetuses at birth and did not account for potential fetal reductions that may have been performed earlier in pregnancy. Objective: To examine the association between fertility treatment and the risk of multifetal pregnancy in a publicly funded fertility program, accounting for both fetal reductions and all live births and stillbirths. Design, Setting, and Participants: This population-based, retrospective cohort study used linked administrative health databases at ICES to examine all births and fetal reductions in Ontario, Canada, from April 1, 2006, to March 31, 2021. Exposure: Mode of conception: (1) unassisted conception, (2) OI/IUI, or (3) IVF. Main Outcomes and Measures: The main outcome was multifetal pregnancy (ie, a twin or higher-order pregnancy). Modified Poisson regression generated adjusted relative risks (ARRs) and derived population attributable fractions (PAFs) for multifetal pregnancies attributable to fertility treatment. Absolute rate differences (ARDs) were used to compare the era before eSET was promoted (2006-2011) with the era after the introduction of the eSET mandate (2016-2021). Results: Of all 1 724 899 pregnancies, 1 670 825 (96.9%) were by unassisted conception (mean [SD] maternal age, 30.6 [5.2] years), 24 395 (1.4%) by OI/IUI (mean [SD] maternal age, 33.1 [4.4] years), and 29 679 (1.7%) by IVF (mean [SD] maternal age, 35.8 [4.7] years). In contrast to unassisted conception, individuals who received OI/IUI or IVF tended to be older, reside in a high-income quintile neighborhood, or have preexisting health conditions. Multifetal pregnancy rates were 1.4% (95% CI, 1.4%-1.4%) for unassisted conception, 10.5% (95% CI, 10.2%-10.9%) after OI/IUI, and 15.5% (95% CI, 15.1%-15.9%) after IVF. Compared with unassisted conception, the ARR of any multifetal pregnancy was 7.0 (95% CI, 6.7-7.3) after OI/IUI and 9.9 (95% CI, 9.6-10.3) after IVF, with corresponding PAFs of 7.1% (95% CI, 7.1%-7.2%) and 13.4% (95% CI, 13.3%-13.4%). Between the eras of 2006 to 2011 and 2016 to 2021, multifetal pregnancy rates decreased from 12.9% to 9.1% with OI/IUI (ARD, -3.8%; 95% CI, -4.2% to -3.4%) and from 29.4% to 7.1% with IVF (ARD, -22.3%; 95% CI, -23.2% to -21.6%). Conclusions and Relevance: In this cohort study of more than 1.7 million pregnancies in Ontario, Canada, a publicly funded IVF program mandating an eSET policy was associated with a reduction in multifetal pregnancy rates. Nevertheless, ongoing strategies are needed to decrease multifetal pregnancy, especially in those undergoing OI/IUI.

Cronicidad: significado construido por los cuidadores y las personas cuidadas / Cronicidade: Significado construído por cuidadores e pessoas cuidadas / Chronicity: Meaning constructed by caregivers and people cared

Introducción: Las enfermedades crónicas no transmisiblesvan en aumento, ocasionando discapacidad y dependenciaen quien la padece, así como la necesidad de un cuidador.La cronicidad es un concepto que se ha analizado desde lamirada de la persona que la padece, dejando un vacío en lacomprensión del significado para el cuidador.Objetivo: Comprender el significado de la cronicidad paralas personas con Enfermedades crónicas no transmisiblesy sus cuidadores informales.Materiales y métodos: Investigación cualitativa fenomenológica-hermenéutica según la propuesta de Van Manen, muestreocasual orientado por criterio, participaron 10 personasenfermas y 9 cuidadores. Los criterios de rigor de credibilidad yconfirmabilidad, confiabilidad y la transferibilidad, garantizaronla calidad del estudio.Resultados: emergieron los siguientes temas: brindar y recibircuidado como un acto de amor; unión de la familia; enfrentarsea la dureza; recibir, brindar y buscar apoyo; estar pendiente;cambio de vida; proceso de aprendizaje; una compañía paratoda la vida; imponer restricciones, limitaciones y pérdidas.Conclusiones: el significado de la cronicidad para loscuidadores y las personas enfermas es complejo, dinámicoy multidimensional; por lo tanto, es necesario realizarintervenciones que ayuden a mitigar el impacto que estaproduce en la vida de este binomio.(AU)

Introduction: Noncommunicable chronic diseasesare rising, causing disability and dependence in theones who suffer from them, as well as the necessityof a caregiver. Chronicity is a concept which has beenanalyzed from the perspective of the ill, leaving a voidin the comprehension of the meaning for the caregiver.Aim: To understand the meaning of chronicity forpeople with non transmissible chronic diseases andtheir informal caregivers.Materials and methods: Qualitative phenomenological-hermeneutic investigation according to the Van Manenproposal, casual sampling orientated by criteria withthe participation of 10 sick people and 9 caregivers.The rigor criteria of credibility and confirmability,reliability, and transferability guaranteed the qualityof the study.Results: The next topics emerged: to offer and receivecare as a love act, family union, facing the hardness,receiving, giving, and looking support, being aware,change of life, learning process, a company for wholelife, imposing restrictions, limitations, and loss.Conclusions: The meaning of chronicity for caregivers andsick people is complex, dynamic, and multidimensionalwhich is why it is important to realize interventionsthat help mitigate the impact in the life of the binomial.(AU)

Introdução: As doenças crônicas não transmissíveisestão aumentando, causando incapacidade e dependênciaem quem as sofre, bem como a necessidade de umcuidador. A cronicidade é um conceito que vem sendoanalisado na perspetiva da pessoa que a sofre, deixandouma lacuna na compreensão de seu significado parao cuidador.Objetivo: compreender o significado da cronicidadepara pessoas com doenças crônicas não transmissíveise seus cuidadores informais.Materiais e métodos: Pesquisa qualitativa fenomenológico-hermenêutica segundo a proposta de Van Manen,amostragem casual orientada por critérios, participaram10 doentes e 9 cuidadores. Os rigorosos critérios decredibilidade e confirmabilidade, confiabilidade etransferibilidade garantiram a qualidade do estudo.Resultados: emergiram os seguintes temas: dar ereceber cuidado como ato de amor; união familiar;enfrentar aspereza; receber, fornecer e buscar apoio;estar pendente; mudança de vida; processo deaprendizagem; uma empresa para a vida; imponharestrições, limitações e perdas.Conclusões: o significado da cronicidade paracuidadores e pessoas doentes é complexo, dinâmicoe multidimensional; portanto, é necessário realizarintervenções que ajudem a mitigar o impacto queisso produz na vida desse binômio.(AU)

Addressing the Rehabilitation Needs of Women Experiencing Infertility in Ethiopia: Time for Action.

The psychological, social, and financial disabilities caused by infertility are significant for women, particularly those living in low- and middle-income countries such as Ethiopia. Although rehabilitation can be an important form of support for such women, infertility is frequently overlooked as a disability or potential target of rehabilitation interventions. This study aimed to determine what rehabilitation-related services and supports are available for women experiencing infertility in Ethiopia. We used an Interpretive Description design. We purposefully selected fourteen rehabilitation, medical, and policy service providers from diverse institutions across three geographical locations. We used semi-structured questions during our in-person and telephone interviews. The data were analyzed using reflexive thematic analysis with the assistance of NVivo. We identified five main themes, including (a) policies related to infertility, (b) the concept that disabilities are physically visible fails to recognize infertility, (c) the need for rehabilitation services for women with infertility, (d) the importance of wellness services for women experiencing infertility, and (e) the role of religion in rehabilitation services. In conclusion, it is essential to strengthen the policies around infertility, incorporate rehabilitation services in fertility care, and view infertility as a disabling condition for women who experience it in Ethiopia.

Observation of naturally canalized phonon polaritons in LiV2O5 thin layers.

Polariton canalization is characterized by intrinsic collimation of energy flow along a single crystalline axis. This optical phenomenon has been experimentally demonstrated at the nanoscale by stacking and twisting van der Waals (vdW) layers of α-MoO3, by combining α-MoO3 and graphene, or by fabricating an h-BN metasurface. However, these material platforms have significant drawbacks, such as complex fabrication and high optical losses in the case of metasurfaces. Ideally, it would be possible to canalize polaritons "naturally" in a single pristine layer. Here, we theoretically predict and experimentally demonstrate naturally canalized phonon polaritons (PhPs) in a single thin layer of the vdW crystal LiV2O5. In addition to canalization, PhPs in LiV2O5 exhibit strong field confinement ( λ p ~ λ 0 27 ), slow group velocity (0.0015c), and ultra-low losses (lifetimes of 2 ps). Our findings are promising for the implementation of low-loss optical nanodevices where strongly directional light propagation is needed, such as waveguides or optical routers.

Assessing preconception exposure to environmental chemicals and fecundity: Strategies, challenges, and research priorities.

In 2022, approximately one out of six people globally experienced infertility at some point in their life. Environmental chemicals, particularly those with endocrine disrupting activity, may contribute to impaired fecundity and infertility. We review existing prospective cohort studies of environmental chemicals and fecundity, identify methodological challenges and biases, and outline future research priorities. Studies of preconception environmental chemical exposures and fecundity have occurred in US, Singapore, China and Denmark with recruitment as early as 1982-1986, as recent as 2015-2017 and sample sizes ranging from 99 to 936. Higher exposure to certain chemicals (e.g. heavy metals, perfluoroalkyl substances) was associated with longer time to pregnancy; yet the literature is scarce or nonexistent for many chemicals. Furthermore, prospective studies face challenges and potential biases related to recruiting participants prior to conception, measuring environmental chemicals during critical windows of exposure, and ascertaining when pregnancy occurred. Research priorities include expanding the scope of biomonitoring data collected during the preconception period, continuing to develop and validate analytic methods for self-sampled biospecimens in traditional and novel matrices, collecting data in male partners and investigating etiologic associations according to indicators of marginalization.

Menopause hormone therapy and physical performance: The Canadian Longitudinal Study on Aging.

OBJECTIVE: To examine the association between menopause hormone therapy (MHT) and physical performance among women from the Canadian Longitudinal Study on Aging. STUDY DESIGN: Cross-sectional study of 12,506 postmenopausal Canadian women. MAIN OUTCOME MEASURES: Grip strength (kg), gait speed (m/s), timed up and go (s), chair rise (s), and balance (s) were assessed following standard procedures. The association between MHT and physical performance was evaluated using linear regression models adjusted for age, education, study site, smoking, alcohol consumption, body mass index, diabetes, hypertension, and hysterectomy. Sensitivity analyses were conducted according to age at study visit (<65 vs. ≥65 years), body mass index (<25 kg/m2 vs. ≥25 kg/m2), physical activity level (less vs. more active), duration and type of MHT, and time of starting MHT after menopause. RESULTS: Compared with those who never used MHT, prior or current use was associated with better performance on the timed up and go test (ß: -0.19; 95%CI: -0.28; -0.11) and faster gait speed (ß = 0.01, 95%CI = 0.00; 0.02). No association was found for grip strength, balance, and chair rise. Results did not change by body mass index, physical activity, or duration of MHT use. When stratified by age at study visit, the effect remained significant only in among those aged 65 years or more. Starting MHT <5 years after menopause was associated with better physical performance. CONCLUSIONS: MHT was associated with better physical performance in gait speed and timed up and go tests. The cross-sectional design of the study limits causal interpretation. Prospective studies are needed to confirm our results.

Endometriosis and mental health: a population-based cohort study.

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.

Transcription levels of hes and their involvement in the biofilm formation of Shiga toxin-producing Escherichia coli O91.

Shiga toxin-producing Escherichia coli (STEC) are recognized as being responsible for many cases of foodborne diseases worldwide. Cattle are the main reservoir of STEC, shedding the microorganisms in their feces. The serogroup STEC O91 has been associated with hemorrhagic colitis and hemolytic uremic syndrome. Locus of Adhesion and Autoaggregation (LAA) and its hes gene are related to the pathogenicity of STEC and the ability to form biofilms. Considering the frequent isolation of STEC O91, the biofilm-forming ability, and the possible role of hes in the pathogenicity of STEC, we propose to evaluate the ability of STEC to form biofilms and to evaluate the expression of hes before and after of biofilm formation. All strains were classified as strong biofilm-forming. The hes expression showed variability between strains before and after biofilm formation, and this may be due to other genes carried by each strain. This study is the first to report the relationship between biofilm formation, and hes expression and proposes that the analysis and diagnosis of LAA, especially hes as STEC O91 virulence factors, could elucidate these unknown mechanisms. Considering that there is no specific treatment for HUS, only supportive care, it is necessary to know the survival and virulence mechanisms of STEC O91.

Periconceptional Serum Creatinine and Risk of Childhood Autism Spectrum Disorder: A Research Letter.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition that manifests in early childhood, in which the maternal metabolic syndrome may be a risk factor. The kidney is a barometer of maternal metabolic syndrome duration and severity. Objective: The main objective of this study is to determine whether periconceptional kidney function is associated with ASD in early childhood. Design Setting and Participants: This retrospective population-based cohort study was completed in Ontario, Canada. Included were singleton children born in an Ontario hospital between April 2007 and March 2021, who were alive at age 48 months and whose mother had a recorded prepregnancy body mass index (BMI) and a measured serum creatinine (SCr) between 120 days preconception and 28 days postconception. Measurement: The main study outcome was a diagnosis of ASD between ages 24 and 48 months. Methods: Relative risks (RRs) of ASD in association with periconceptional SCr were generated using modified Poisson regression and adjusted for several confounders. Results: The cohort comprised 86 054 women, who had 89 677 liveborn children surviving to at least 48 months of age. There was no significant association between periconceptional SCr and ASD (RR: 0.86; 95 % confidence interval: [0.67, 1.10]). Limitations: Selection bias may have arisen had SCr been ordered on clinical grounds. Conclusions: Further study is warranted to determine whether prepregnancy glomerular hyperfiltration is a marker of ASD and other behavioral conditions in childhood. To do so, a more accurate measure of hyperfiltration is needed than SCr.

Contexte: Des problèmes d'innocuité sont détectés dans environ un tiers des médicaments d'ordonnance au cours des années qui suivent leur approbation par l'organisme de réglementation. Les personnes âgées, en particulier celles qui sont atteintes d'insuffisance rénale chronique, sont particulièrement exposées aux effets indésirables des médicaments d'ordonnance. Ce protocole décrit une nouvelle approche qui, à partir des données administratives du système de santé, pourrait permettre d'identifier plus efficacement les signaux crédibles sur la sécurité des médicaments. Objectif: Utiliser l'informatique à haut débit et l'automatisation pour mener plus de 700 études de cohorte sur l'innocuité des médicaments chez les adultes âgés résidant en Ontario (Canada). Chaque étude comparera 74 résultats aigus (30 jours) chez des patients qui commencent un nouveau médicament sur ordonnance (nouveaux utilisateurs) à ceux d'un groupe de non-utilisateurs avec des caractéristiques de santé initiales similaires. Les risques seront évalués par strates de la fonction rénale initiale. Cadre et type d'étude: Études populationnelles de cohortes de nouveaux utilisateurs de médicaments menées à l'aide des bases de données administratives couplées du système de santé ontarien (Canada). Période étudiée: du 1er janvier 2008 au 1er mars 2020. Population source: les Ontariens de 66 ans ou plus ayant rempli au moins une ordonnance pour patient non hospitalisé par l'entremise du Program de médicaments de l'Ontario (PMO) pendant la période de l'étude (tous les résidents de la province bénéficient d'un système de soins de santé universel; les personnes âgées de 65 ans et plus bénéficient d'une couverture universelle des médicaments d'ordonnance par l'intermédiaire du PMO). Sujets: Nous avons identifié 3,2 millions d'adultes âgés dans la population source au cours de la période d'étude et constitué plus de 700 cohortes de médicaments, chacune contenant des groupes mutuellement exclusifs de nouveaux utilisateurs et de non-utilisateurs. Les non-utilisateurs se sont vu attribuer au hasard des dates d'entrée dans la cohorte qui suivaient les dates de début d'ordonnance des nouveaux utilisateurs. Les critères d'admissibilité étaient d'avoir une mesure initiale du débit de filtration glomérulaire estimé [DFGe] dans les 12 mois précédant la date d'entrée dans la cohorte (dans le groupe des nouveaux utilisateurs, le délai médian était de 71 jours avant l'entrée dans la cohorte), ne pas suivre de dialyze chronique, ne pas avoir eu de greffe rénale et n'avoir jamais eu de prescription d'un médicament de la même sous-classe que le médicament à l'étude. Les nouveaux utilisateurs et les non-utilisateurs seront jumelés selon environ 400 caractéristiques de santé initiales à l'aide de la probabilité inverse de traitement pondérée selon les scores de propension dans les trois strates de mesure du DFGe initial: ≥60 ml/min/1,73 m2; 45 à <60 ml/min/1,73 m2 et <45 ml/min/1,73 m2. Résultats: Nous comparerons les groupes de nouveaux utilisateurs et de non-utilisateurs selon 74 critères de jugement cliniquement pertinents (17 critères composites et 57 critères individuels) pendant les 30 jours suivant l'entrée dans la cohorte. Une approche prédéfinie a permis de déterminer ces 74 résultats. Plan d'analyze statistique: Dans chaque cohorte, nous calculerons les différences de risque (par régression de Poisson) et les rapports de risque (par régression binomiale) pondérés pour chaque strate de DFGe. Les interactions additives et multiplicatives par catégorie de DFGe seront examinées. Les associations médicaments-résultats répondant à des critères prédéfinis (signaux identifiés) seront examinées plus avant dans des analyses supplémentaires (survie, exposition à des témoins négatifs, analyses de la valeur E, etc.) et des visualizations. Résultats: Dans les cohortes initiales de médicaments, les médianes sont de 6 120 nouveaux utilisateurs (intervalle interquartile de 1 469 à 38 839) et de 1 088 301 non-utilisateurs (intervalle interquartile de 751 697 à 1 267 009). Les médicaments comptant le plus grand nombre de nouveaux utilisateurs sont le trihydrate d'amoxicilline (n = 1 000 032), la céfalexine (n = 571 566), l'acétaminophène sur ordonnance (n = 571 563) et la ciprofloxacine (n = 504 374). De 19 à 29 % des nouveaux utilisateurs dans ces cohortes présentaient un DFGe < 60 ml/min/1,73 m2. Limites: Malgré l'utilization de techniques robustes pour équilibrer les indicateurs de base et pour contrôler le risque de confusion par indication, il pourrait subsister des facteurs de confusion résiduels. Seuls les résultats aigus (30 jours) seront examinés. Nos sources de données ne comprennent pas les médicaments sans ordonnance (en vente libre) ni les médicaments prescrits dans les hôpitaux, et n'incluent pas l'utilization de médicaments sur ordonnance en ambulatoire chez les enfants ou les adultes de moins de 65 ans. Conclusion: Cette approche accélérée pour la réalisation d'études d'innocuité des médicaments après leur mise en marché a le potentiel de détecter efficacement les effets indésirables de ces médicaments dans une population vulnérable. Les résultats de ce protocole serviront à améliorer l'innocuité des médicaments.

Maternal exposure to metals and time-to-pregnancy: The MIREC cohort study.

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.

Miscarriage after SARS-CoV-2 vaccination: A population-based cohort study.

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.

Polycystic Ovary Syndrome, Gestational Diabetes Mellitus, and the Mediating Role of Obesity: A Population-Based Cohort Study.

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.

Protein S antibody as an adjunct therapy for hemophilia B.

ABSTRACT: Hemophilia B (HB) is caused by an inherited deficiency of plasma coagulation factor IX (FIX). Approximately 60% of pediatric patients with HB possess a severe form of FIX deficiency (<1% FIX activity). Treatment typically requires replacement therapy through the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant protein S (PS) inhibits activated FIX (FIXa). PS ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercially obtained plasma and plasma from pediatric patients with HB. We included 11 pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of the FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Furthermore, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.