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BACKGROUND: Measurement of rat anogenital distance (AGD) dates to at least 1912. Increased interest in endocrine disrupting chemicals and the use of AGD as a biomarker for fetal androgen effects have increased the number of studies with this endpoint in recent decades. A literature review revealed different landmarks, methods of measurement, and methods to adjust for body weight differences. AGD is often reported to hundredths of millimeters and as such, deserves precision in all these aspects. This paper presents recommendations for the measurement and analysis of rodent AGD. METHODS: Literature and regulatory guidance documents that mentioned or measured rodent AGD were reviewed. Four adjustment methods were evaluated using available online data from three rat studies each with two generations of offspring. RESULTS: Tabulation of studies reveals that species/stocks and time of data collection, but more importantly anatomical landmarks and methods of measurement have produced a variety of results which are difficult to compare. Not all studies have adjusted for test article effects on body weight (and thus size). The four adjustment methods were fairly comparable. CONCLUSION: Recommendations are as follows. A microscopic method should be used to measure AGD of late rodent fetuses and early postnatal pups. The caudal edge of the genital tubercle and the cranial edge of the anus are clear and identifiable landmarks. The simplest adjustment is to divide individual AGDs by the cube root of animals' body weight. These recommendations will help ensure data consistency and accuracy, and facilitate meaningful comparisons across laboratories and chemical classes.
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Canal Anal , Animales , Ratas , Canal Anal/anatomía & histología , Canal Anal/embriología , Femenino , Masculino , Embarazo , Roedores/anatomía & histología , Peso Corporal , Feto/anatomía & histología , Genitales/anatomía & histología , Genitales/embriologíaRESUMEN
Tissue engineering encompasses a range of techniques that direct the growth of cells into a living tissue construct for regenerative medicine applications, disease models, drug discovery, and safety testing. These techniques have been implemented to alleviate the clinical burdens of impaired healing of skin, bone, and other tissues. Construct development requires the integration of tissue-specific cells and/or an extracellular matrix-mimicking biomaterial for structural support. Production of such constructs is generally expensive and environmentally costly, thus eco-sustainable approaches should be explored. Pulsed electric field (PEF) technology is a nonthermal physical processing method commonly used in food production and biomedical applications. In this review, the key principles of PEF and the application of PEF technology for skin engineering will be discussed, with an emphasis on how PEF can be applied to skin cells to modify their behaviour, and to biomaterials to assist in their isolation or sterilisation, or to modify their physical properties. The findings indicate that the success of PEF in tissue engineering will be reliant on systematic evaluation of key parameters, such as electric field strength, and their impact on different skin cell and biomaterial types. Linking tangible input parameters to biological responses critical to healing will assist with the development of PEF as a sustainable tool for skin repair and other tissue engineering applications.
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BACKGROUND: A new derived (i.e., calculated) endpoint of developmental toxicology has appeared in a very few studies since 1990. This endpoint is adjusted mean live fetal weight per litter or adjusted fetal weight. Given our lack of familiarity with the endpoint, we evaluated the basis, prevalence, methods, and usefulness in embryo-fetal developmental toxicity (EFDT) studies in rats. METHODS: Literature searches were performed with key terms using PubMed and Google Scholar. Major textbooks were consulted but lack of any mention of the endpoint. Unpublished EFDT data, which are readily available online, were utilized to test adjustment methods. RESULTS: Pertinent information on factors that influence fetal weight goes back a century. Four papers utilizing rats were found in which fetal weights were adjusted using either statistical or formula-based methods to adjust fetal weights. Only one study showed a clear benefit to the endpoint when there was a marked decrease in live litter size; this pointed to situations in which the new endpoint might be useful. The lone formula-based adjustment method was found to be lacking adequate testing and justifications. A new experimental alternative formula-based adjustment is shown to produce results very similar to statistical methods. CONCLUSIONS: From this assessment, we recommend that adjusted fetal weight should not be a routine endpoint at this time. However, there are likely cases where this derived endpoint could aid interpretation. We encourage other investigators to examine previous EFDT study data to establish guidance on the use of adjusted mean live fetal weights.
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Peso Fetal , Embarazo , Femenino , Ratas , Animales , Tamaño de la CamadaRESUMEN
STUDY QUESTION: To what extent do self-reported sleep duration and non-daytime work schedules in either partner affect the rate of spontaneous abortion (SAB)? SUMMARY ANSWER: Incidence of SAB had little association with female sleep duration and a modest positive association with male short sleep duration, female work at night, and discrepant work schedules among partners. WHAT IS KNOWN ALREADY: Several studies have reported an association between short sleep duration in either partner and reproductive health outcomes, including fecundability. Moreover, certain types of female occupational exposures during pregnancy have been associated with an increased risk of SAB. No studies have evaluated SAB risk in relation to male sleep and work schedules, or joint exposures within a couple. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 9357 female participants and 2602 of their male partners residing in North America (June 2013 to April 2023). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants enrolled when they were attempting pregnancy and completed self-administered baseline questionnaires about their average sleep duration and work schedules. Among those who conceived, we ascertained SAB and gestational age at loss via follow-up questionnaires. We used multivariable Cox proportional hazards models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% CIs relating SAB with sleep duration and non-daytime work schedules for female and male participants, and the couple. We used inverse probability weighting to account for potential selection bias due to the possibility of differential participation of male partners with respect to the exposures. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to female participants with recommended sleep (7-8.9 h), those reporting short sleep duration (<6 h) did not have a higher rate of SAB (HR 0.88, 95% CI 0.69, 1.13). Short self-reported sleep duration among male participants was modestly associated with a higher rate of SAB (adjusted and weighted HR 1.30, 95% CI 0.96, 1.75). Female night work at night (adjusted HR 1.19, 95% CI 1.02, 1.38) and male non-daytime work (adjusted and weighted HR 1.26, 95% CI 1.00, 1.59) were associated with modestly higher rates of SAB, whereas female rotating shift work was not (adjusted HR 0.91, 0.78, 1.05) compared with daytime workers. Couples in which work schedules were discrepant had an elevated rate of SAB if the male partner worked a non-daytime shift (adjusted and weighted HR 1.46, 95% CI 1.13, 1.88) compared with couples in which both members worked during the day. The corresponding HR if only the female partner worked a non-daytime shift was 1.21 (95% CI 0.92, 1.58). LIMITATIONS, REASONS FOR CAUTION: Data on sleep duration and work schedules were based on self-report, which is vulnerable to misclassification, particularly since participants were asked to report their average sleep duration during the past month. Work exposures were heterogeneous, as many different types of employment may require night and shift work and may have different associations with SAB. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are consistent with previous research indicating that some types of female employment schedules may be associated with SAB incidence. This is the first study to indicate a relationship between SAB and male employment schedules, indicating that discrepant work schedules within a couple might be relevant. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grants R01HD105863 (PIs: L.A.W. and M.L.E.), R01HD086742 (PIs: L.A.W. and E.E.H.), and R21HD072326 (PI: L.A.W.). PRESTO has received in-kind donations from Swiss Precision Diagnostics and Kindara.com for primary data collection. L.A.W. is a consultant for AbbVie, Inc. and the Gates Foundation. M.L.E. is an advisor for and holds stock in Ro, Hannah, Dadi, Underdog, Vseat, & Doveras. The other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.
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Aborto Espontáneo , Horario de Trabajo por Turnos , Embarazo , Niño , Humanos , Masculino , Femenino , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Incidencia , Estudios Prospectivos , Duración del SueñoRESUMEN
Observational research provides valuable opportunities to advance oral health science but is limited by vulnerabilities to systematic bias, including unmeasured confounding, errors in variable measurement, or bias in the creation of study populations and/or analytic samples. The potential influence of systematic biases on observed results is often only briefly mentioned among the discussion of limitations of a given study, despite existing methods that support detailed assessments of their potential effects. Quantitative bias analysis is a set of methodological techniques that, when applied to observational data, can provide important context to aid in the interpretation and integration of observational research findings into the broader body of oral health research. Specifically, these methods were developed to provide quantitative estimates of the potential magnitude and direction of the influence of systematic biases on observed results. We aim to encourage and facilitate the broad adoption of quantitative bias analyses into observational oral health research. To this end, we provide an overview of quantitative bias analysis techniques, including a step-by-step implementation guide. We also provide a detailed appendix that guides readers through an applied example using real data obtained from a prospective observational cohort study of preconception periodontitis in relation to time to pregnancy. Quantitative bias analysis methods are available to all investigators. When appropriately applied to observational studies, findings from such studies can have a greater impact in the broader research context.
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Proyectos de Investigación , Femenino , Humanos , Embarazo , Sesgo , Estudios ProspectivosAsunto(s)
COVID-19 , Ivermectina , Femenino , Humanos , Ivermectina/toxicidad , Embarazo , SARS-CoV-2RESUMEN
STUDY QUESTION: Is a history of periodontitis among women associated with reduced fecundability? SUMMARY ANSWER: A history of periodontitis, as assessed by three different self-reported measures, may be associated with reduced fecundability. WHAT IS KNOWN ALREADY: Periodontitis is a chronic inflammatory condition affecting the hard and soft tissues surrounding the teeth. Few studies have evaluated the association between periodontitis and time to pregnancy, and findings are mixed. It is hypothesized that periodontitis may adversely affect time to pregnancy. STUDY DESIGN, SIZE, DURATION: We conducted a prospective cohort study of 2764 female pregnancy planners residing in North America (March 2015-June 2020). PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible participants had been attempting pregnancy for six or fewer menstrual cycles at enrollment and were not using fertility treatment. Women answered questions about their oral health. Pregnancy was ascertained via bi-monthly follow-up questionnaires. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs) for three different measures indicative of a history of periodontitis: ever diagnosed with periodontitis (N = 265), ever received treatment for periodontitis (N = 299), and ever had an adult tooth become loose on its own (N = 83). We adjusted for potential confounders and precision variables. Women at risk of misclassification of periodontitis diagnosis due to pregnancy-related gingivitis were reclassified in a sensitivity analysis. MAIN RESULTS AND THE ROLE OF CHANCE: All three indices of periodontitis may be associated with reduced fecundability. FRs were 0.89 (95% CI 0.75-1.06) comparing women with and without a previous periodontitis diagnosis, 0.79 (95% CI 0.67-0.94) comparing women with and without previous periodontitis treatment, and 0.71 (95% CI 0.44-1.16) comparing women with and without a tooth that became loose. After reclassification of pregnancy-related gingivitis in the sensitivity analysis, the FR for periodontitis diagnosis was 0.83 (95% CI 0.68-1.00). Weaker FRs were observed among parous women as compared with nulliparous women for periodontitis diagnosis and tooth becoming loose, but not for periodontitis treatment. LIMITATIONS, REASONS FOR CAUTION: Though we used validated self-report measures of periodontitis, clinical confirmation is the gold standard. These questions may be functioning as markers of different levels of periodontitis severity, but we were unable to measure disease severity in this population. Finally, we cannot eliminate the possibility of unmeasured confounding. WIDER IMPLICATIONS OF THE FINDINGS: This is the first preconception prospective cohort study to evaluate the association between self-reported periodontitis and fecundability. Our results indicate that periodontitis may be associated with lower fecundability. STUDY FUNDING/COMPETING INTEREST(S): This work was partially funded by R01HD086742/Eunice Kennedy Shriver National Institute of Child Health and Human Development and R21HD072326/Eunice Kennedy Shriver National Institute of Child Health and Human Development. PRESTO has received in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, FertilityFriend.com, and Kindara.com for primary data collection. L.A.W. is a fibroid consultant for AbbVie, Inc. J.C.B., S.W., J.Y., K.J.R., E.E.H., and B.H. have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.
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Fertilidad , Periodontitis , Adulto , Niño , Femenino , Humanos , Ciclo Menstrual , Periodontitis/complicaciones , Periodontitis/diagnóstico , Periodontitis/epidemiología , Embarazo , Estudios Prospectivos , Autoinforme , Tiempo para Quedar EmbarazadaRESUMEN
STUDY QUESTION: How accurately do women report a diagnosis of endometriosis on self-administered questionnaires? SUMMARY ANSWER: Based on the analysis of four international cohorts, women self-report endometriosis fairly accurately with a > 70% confirmation for clinical and surgical records. WHAT IS KNOWN ALREADY: The study of complex diseases requires large, diverse population-based samples, and endometriosis is no exception. Due to the difficulty of obtaining medical records for a condition that may have been diagnosed years earlier and for which there is no standardized documentation, reliance on self-report is necessary. Only a few studies have assessed the validity of self-reported endometriosis compared with medical records, with the observed confirmation ranging from 32% to 89%. STUDY DESIGN, SIZE, DURATION: We compared questionnaire-reported endometriosis with medical record notation among participants from the Black Women's Health Study (BWHS; 1995-2013), Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N; 1990-2006), Growing Up Today Study (GUTS; 2005-2016), and Nurses' Health Study II (NHSII; 1989-1993 first wave, 1995-2007 second wave). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants who had reported endometriosis on self-administered questionnaires gave permission to procure and review their clinical, surgical, and pathology medical records, yielding records for 827 women: 225 (BWHS), 168 (E3N), 85 (GUTS), 132 (NHSII first wave), and 217 (NHSII second wave). We abstracted diagnosis confirmation as well as American Fertility Society (AFS) or revised American Society of Reproductive Medicine (rASRM) stage and visualized macro-presentation (e.g. superficial peritoneal, deep endometriosis, endometrioma). For each cohort, we calculated clinical reference to endometriosis, and surgical- and pathologic-confirmation proportions. MAIN RESULTS AND THE ROLE OF CHANCE: Confirmation was high-84% overall when combining clinical, surgical, and pathology records (ranging from 72% for BWHS to 95% for GUTS), suggesting that women accurately report if they are told by a physician that they have endometriosis. Among women with self-reported laparoscopic confirmation of their endometriosis diagnosis, confirmation of medical records was extremely high (97% overall, ranging from 95% for NHSII second wave to 100% for NHSII first wave). Importantly, only 42% of medical records included pathology reports, among which histologic confirmation ranged from 76% (GUTS) to 100% (NHSII first wave). Documentation of visualized endometriosis presentation was often absent, and details recorded were inconsistent. AFS or rASRM stage was documented in 44% of NHSII first wave, 13% of NHSII second wave, and 24% of GUTS surgical records. The presence/absence of deep endometriosis was rarely noted in the medical records. LIMITATIONS, REASONS FOR CAUTION: Medical record abstraction was conducted separately by cohort-specific investigators, potentially introducing misclassification due to variation in abstraction protocols and interpretation. Additionally, information on the presence/absence of AFS/rASRM stage, deep endometriosis, and histologic findings were not available for all four cohort studies. WIDER IMPLICATIONS OF THE FINDINGS: Variation in access to care and differences in disease phenotypes and risk factor distributions among patients with endometriosis necessitates the use of large, diverse population samples to subdivide patients for risk factor, treatment response and discovery of long-term outcomes. Women self-report endometriosis with reasonable accuracy (>70%) and with exceptional accuracy when women are restricted to those who report that their endometriosis had been confirmed by laparoscopic surgery (>94%). Thus, relying on self-reported endometriosis in order to use larger sample sizes of patients with endometriosis appears to be valid, particularly when self-report of laparoscopic confirmation is used as the case definition. However, the paucity of data on histologic findings, AFS/rASRM stage, and endometriosis phenotypic characteristics suggests that a universal requirement for harmonized clinical and surgical data documentation is needed if we hope to obtain the relevant details for subgrouping patients with endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by Eunice Kennedy Shriver National Institute of Child Health and Development grants HD48544, HD52473, HD57210, and HD94842, National Cancer Institute grants CA50385, R01CA058420, UM1CA164974, and U01CA176726, and National Heart, Lung, and Blood Institute grant U01HL154386. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. AS, SM, and KT were additionally supported by the J. Willard and Alice S. Marriott Foundation. MK was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078) and is grateful to the Philippe Foundation and the Bettencourt-Schueller Foundation for their financial support. Funders had no role in the study design, conduct of the study or data analysis, writing of the report, or decision to submit the article for publication. LA Wise has served as a fibroid consultant for AbbVie, Inc for the last three years and has received in-kind donations (e.g. home pregnancy tests) from Swiss Precision Diagnostics, Sandstone Diagnostics, Kindara.com, and FertilityFriend.com for the PRESTO cohort. SA Missmer serves as an advisory board member for AbbVie and a single working group service for Roche; neither are related to this study. No other authors have a conflict of interest to report. Funders had no role in the study design, conduct of the study or data analysis, writing of the report, or decision to submit the article for publication. TRIAL REGISTRATION NUMBER: N/A.
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Endometriosis , Niño , Estudios de Cohortes , Endometriosis/diagnóstico , Endometriosis/epidemiología , Femenino , Fertilidad , Humanos , Embarazo , Factores de Riesgo , AutoinformeRESUMEN
STUDY QUESTION: To what extent is exposure to cellular telephones associated with male fertility? SUMMARY ANSWER: Overall, we found little association between carrying a cell phone in the front pants pocket and male fertility, although among leaner men (BMI <25 kg/m2), carrying a cell phone in the front pants pocket was associated with lower fecundability. WHAT IS KNOWN ALREADY: Some studies have indicated that cell phone use is associated with poor semen quality, but the results are conflicting. STUDY DESIGN, SIZE, DURATION: Two prospective preconception cohort studies were conducted with men in Denmark (n = 751) and in North America (n = 2349), enrolled and followed via the internet from 2012 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: On the baseline questionnaire, males reported their hours/day of carrying a cell phone in different body locations. We ascertained time to pregnancy via bi-monthly follow-up questionnaires completed by the female partner for up to 12 months or until reported conception. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs) for the association between male cell phone habits and fecundability, focusing on front pants pocket exposure, within each cohort separately and pooling across the cohorts using a fixed-effect meta-analysis. In a subset of participants, we examined selected semen parameters (semen volume, sperm concentration and sperm motility) using a home-based semen testing kit. MAIN RESULTS AND THE ROLE OF CHANCE: There was little overall association between carrying a cell phone in a front pants pocket and fecundability: the FR for any front pants pocket exposure versus none was 0.94 (95% CI: 0.0.83-1.05). We observed an inverse association between any front pants pocket exposure and fecundability among men whose BMI was <25 kg/m2 (FR = 0.72, 95% CI: 0.59-0.88) but little association among men whose BMI was ≥25 kg/m2 (FR = 1.05, 95% CI: 0.90-1.22). There were few consistent associations between cell phone exposure and semen volume, sperm concentration, or sperm motility. LIMITATIONS, REASONS FOR CAUTION: Exposure to radiofrequency radiation from cell phones is subject to considerable non-differential misclassification, which would tend to attenuate the estimates for dichotomous comparisons and extreme exposure categories (e.g. exposure 8 vs. 0 h/day). Residual confounding by occupation or other unknown or poorly measured factors may also have affected the results. WIDER IMPLICATIONS OF THE FINDINGS: Overall, there was little association between carrying one's phone in the front pants pocket and fecundability. There was a moderate inverse association between front pants pocket cell phone exposure and fecundability among men with BMI <25 kg/m2, but not among men with BMI ≥25 kg/m2. Although several previous studies have indicated associations between cell phone exposure and lower sperm motility, we found few consistent associations with any semen quality parameters. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the National Institutes of Health, grant number R03HD090315. In the last 3 years, PRESTO has received in-kind donations from Sandstone Diagnostics (for semen kits), Swiss Precision Diagnostics (home pregnancy tests), Kindara.com (fertility app), and FertilityFriend.com (fertility app). Dr. L.A.W. is a fibroid consultant for AbbVie, Inc. Dr. H.T.S. reports that the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to and administered by Aarhus University. None of these studies are related to the current study. Dr. M.L.E. is an advisor to Sandstone Diagnostics, Ro, Dadi, Hannah, and Underdog. Dr. G.J.S. holds ownership in Sandstone Diagnostics Inc., developers of the Trak Male Fertility Testing System. In addition, Dr. G.J.S. has a patent pending related to Trak Male Fertility Testing System issued. TRIAL REGISTRATION NUMBER: N/A.
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Teléfono Celular , Tiempo para Quedar Embarazada , Estudios de Cohortes , Femenino , Fertilidad , Humanos , Masculino , Embarazo , Estudios Prospectivos , Análisis de Semen , Motilidad EspermáticaRESUMEN
STUDY QUESTION: Does male alcohol consumption affect fecundability? SUMMARY ANSWER: In data pooled across Danish and North American preconception cohort studies, we found little evidence of an association between male alcohol consumption and reduced fecundability. WHAT IS KNOWN ALREADY: Experimental and clinical studies have shown that alcohol affects male reproductive physiology, mainly by altering male reproductive hormones and spermatogenesis. However, few epidemiologic studies have examined the association between alcohol consumption and male fertility. STUDY DESIGN, SIZE, DURATION: Data were collected from two ongoing prospective preconception cohort studies: the Danish 'SnartForaeldre' (SF) study (662 couples) and the North American 'Pregnancy Study Online' (PRESTO) (2017 couples). Participants included in the current analysis were enrolled from August 2011 through June 2019 (SF) and from June 2013 through June 2019 (PRESTO). PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible men were aged ≥18 years in SF and ≥21 years in PRESTO, in a stable relationship with a female partner and not using contraception or receiving fertility treatment. In both cohorts, alcohol consumption/serving size was self-reported as number of beers (330 mL/12 oz.), glasses of white or red wine (120 mL/4 oz. each), dessert wine (50 mL/2 oz.) and spirits (20 mL/1.5 oz.). Overall alcohol consumption was categorized as none, 1-5, 6-13 and ≥14 standard servings per week. Total menstrual cycles at risk were calculated using data from female partners' follow-up questionnaires, which were completed every 8 weeks until self-reported pregnancy or 12 menstrual cycles, whichever came first. Analyses were restricted to couples that had been trying to conceive for ≤6 cycles at study entry. Proportional probability regression models were used to compute fecundability ratios (FRs) and 95% confidence interval (CIs). We adjusted for male and female age, female partner's alcohol consumption, intercourse frequency, previous history of fathering a child, race/ethnicity, education, BMI, smoking and consumption of sugar-sweetened beverages and caffeine. MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative proportion of couples who conceived during 12 cycles of follow-up were 1727 (64.5%). The median (interquartile range) of total male alcohol consumption was 4.5 (2.0-7.8) and 4.1 (1.0-8.6) standard servings per week in the SF and PRESTO cohorts, respectively. In pooled analyses, adjusted FRs for male alcohol consumption of 1-5, 6-13 and ≥14 standard servings per week compared with no alcohol consumption were 1.02 (95% CI: 0.90-1.17), 1.10 (95% CI: 0.96-1.27) and 0.98 (95% CI: 0.81-1.18), respectively. For SF, adjusted FRs of 1-5, 6-13 and ≥14 standard servings per week compared with no alcohol consumption were 0.97 (95% CI: 0.73-1.28), 0.81 (95% CI: 0.60-1.10) and 0.82 (95% CI: 0.51-1.30), respectively. For PRESTO, adjusted FRs of 1-5, 6-13 and ≥14 standard servings per week compared with no alcohol consumption were 1.02 (95% CI: 0.88-1.18), 1.20 (95% CI: 1.03-1.40) and 1.03 (95% CI: 0.84-1.26), respectively. LIMITATIONS, REASONS FOR CAUTION: Male alcohol consumption was ascertained at baseline only, and we did not distinguish between regular and binge drinking. In addition, we had insufficient numbers to study the effects of specific types of alcoholic beverages. As always, residual confounding by unmeasured factors, such as dietary factors and mental health, cannot be ruled out. Comorbidities thought to play a role in the reproductive setting (i.e. cancer, metabolic syndrome) were not considered in this study; however, the prevalence of cancer and diabetes was low in this age group. Findings for the highest categories of alcohol consumption (6-13 and ≥14 servings/week) were not consistent across the two cohorts. WIDER IMPLICATIONS OF THE FINDINGS: Despite little evidence of an association between male alcohol consumption and reduced fecundability in the pooled analysis, data from the Danish cohort might indicate a weak association between reduced fecundability and consumption of six or more servings per week. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Institutes of Health (R01-HD060680, R01-HD086742, R21-HD050264, R21-HD072326, R03-HD090315), the Novo Nordisk Foundation, Oticon Fonden, Politimester J.P.N. Colind og hustru Asmine Colinds mindelegat and Erna og Peter Houtveds studielegat. PRESTO receives in-kind donations from FertilityFriend.com, Kindara.com, Swiss Precision Diagnostics and Sandstone Diagnostics for the collection of data pertaining to fertility. Dr Wise serves as a consultant on uterine leiomyomata for AbbVie.com. All other authors declare no conflict of interest.
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Fertilidad , Fertilización , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Embarazo , Estudios ProspectivosRESUMEN
Despite personal safety apps claiming to increase safety, few studies have examined the usefulness of such apps in reducing public stranger violence. A content analysis of personal safety apps available in the iTunes store and Google Play identified location-based services, personal alarms, crowd-sourced hot spot data, and geofencing as the most common features. The majority of apps offered interventions either at the time of the event or post-event, suggesting that they may reduce a user's fear of crime but have limited usefulness in reducing vulnerability to victimization. Implications for users, app designers, and key stakeholders are discussed.
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Formación de Concepto , Aplicaciones Móviles/normas , Seguridad del Paciente/normas , Australia , Humanos , Aplicaciones Móviles/estadística & datos numéricos , Seguridad del Paciente/estadística & datos numéricosRESUMEN
The equine parasite Theilera equi continues to curtail global equine commerce due primarily to its ability to persist indefinitely in the immunocompetent horse. Details regarding the parasite life cycle, pathogenesis and mechanism of persistence remain unclear. The recently discovered T. haneyi is also capable of persistence in the horse, creating a potential reservoir for additional infections. These two divergent parasites share a unique gene family that expresses surface merozoite antigens, or equi merozoite antigens (EMAs). The EMA family was maintained in number and size in both parasites despite a species divergence of over 30 million years ago. This family is unique amongst Theilerias in number, structure and biochemical properties. In silico analysis revealed no evidence of selection for diversity within this family, indicating a role in host adaptation and persistence rather than antigenic variation and immune escape. Biochemical analysis revealed the presence of a conserved domain, homologous to the hemolysin toxin found in cobra venom. This finding combined with data from protein interaction prediction models may indicate interaction with the structural components of the host erythrocyte and a role in merozoite entry or escape. Additional predicted protein interactions focus on disruption of the enzymatic functions of the host cell, potentially resulting in enhanced parasite survival.
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Antígenos de Protozoos/inmunología , Evolución Biológica , Enfermedades de los Caballos/inmunología , Enfermedades de los Caballos/parasitología , Theileria/inmunología , Theileriosis/inmunología , Theileriosis/parasitología , Secuencia de Aminoácidos , Animales , Antígenos de Protozoos/química , Antígenos de Protozoos/genética , Biodiversidad , Codón , Secuencia Conservada , Genoma de Protozoos , Caballos , Interacciones Huésped-Parásitos/inmunología , Merozoítos/inmunología , Theileria/genéticaAsunto(s)
Alcaloides de la Vinca , Animales , Suplementos Dietéticos , Desarrollo Fetal , Conejos , RatasRESUMEN
GARDASIL®9, a 9-valent vaccine against human papillomavirus (9vHPV), was developed to prevent diseases mediated by HPV types 6/11/16/18/31/33/45/52/58. During the development of the vaccine, three nonclinical safety studies were conducted to evaluate repeat-dose toxicity and prenatal and postnatal developmental toxicity in Sprague-Dawley rats. In all studies, the vaccine was administered via intramuscular injections of 0.5â¯mL (the human dose) divided equally into each quadriceps muscle. In the repeat-dose toxicity study, potential local and systemic toxic effects of the 9vHPV vaccine were evaluated after 4 doses given 21â¯days apart and after a 21-day recovery period. In the prenatal study, virgin females were dosed at 5 and 2â¯weeks prior to mating and on Gestation Day [GD] 6 (3 total doses). Potential postnatal developmental toxicity of the vaccine formulation was evaluated after 4 total doses (premating to lactation). There were no treatment-related unscheduled deaths in any studies. In the 3-month repeat-dose toxicity study, no adverse effects in male or female rats were observed. Anticipated systemic effects representing immunological responses and local inflammatory reactions at the injection sites were noted in the vaccine-treated groups, with a trend toward recovery by the end of the 21-day recovery period. In the prenatal developmental toxicity study, there was no evidence of toxicity in females given the vaccine. There were no effects on fertility or reproductive performance of the parental females and no evidence of developmental toxicity. In the postnatal study, there was no evidence of toxicity in vaccine-treated females and no evidence of developmental toxicity based on standard postnatal parameters, including behavioral testing and reproductive performance. The vaccine induced antibody responses in all studies and vaccine-specific antibodies were detected in offspring in the developmental toxicity studies. These results support the favorable safety profile of GARDASIL®9.
Asunto(s)
Exposición Materna , Vacunas contra Papillomavirus/toxicidad , Reproducción , Animales , Anticuerpos Antivirales/sangre , Femenino , Fertilidad , Lactancia , Papillomaviridae , Embarazo , Ratas , Ratas Sprague-Dawley , Pruebas de ToxicidadRESUMEN
OBJECTIVE: To assess the extent to which lubricant use during intercourse is associated with time to pregnancy (TTP). DESIGN: Prospective cohort study. SETTING: Denmark and North America. POPULATION: A total of 6467 women aged 18-49 years who were not using contraception or fertility treatment. METHODS: We pooled data from two continuing prospective cohort studies of pregnancy planners in Denmark (2011-2017) and North America (2013-2017). Female participants completed bimonthly questionnaires for 12 months or until they reported pregnancy. After restricting the study to women without a history of infertility who had been trying to conceive for six or fewer cycles at enrollment, 6467 women were retained for analysis. Self-reported lubricant use was categorised as water-based/not pH balanced, water-based/pH balanced 'fertility friendly', silicone-based, oil-based, or a combination of these. We used proportional probability models to calculate fecundability ratios (FRs) and 95% confidence intervals (95% CIs) for the association between lubricant use and fecundability, after adjusting for cohort and sociodemographic and lifestyle factors. MAIN OUTCOME MEASURE: Fecundability. RESULTS: At baseline, 17.5% of participants reported the use of lubricants, most commonly water-based/not pH balanced (11.4%). Compared with non-use of lubricants, FRs were 1.02 (95% CI 0.93-1.11) for water-based/not pH-balanced lubricant use, 1.01 (95% CI 0.86-1.18) for water-based/pH balanced 'fertility friendly' lubricant use, 1.23 (95% CI 0.94-1.61) for oil-based lubricant use, and 1.27 (95% CI 0.93-1.73) for silicone-based lubricant use. Associations between oil-based lubricant use and fecundability were inconsistent across subgroups of study cohort, age, parity, and intercourse frequency. CONCLUSIONS: Lubricant use was not associated with reduced fecundability in the preconception cohorts of pregnancy planners studied. TWEETABLE ABSTRACT: Lubricant use during intercourse was not associated with time to pregnancy in a study of pregnancy planners.