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Abstract Practice questions are highly sought out for use as a study tool among medical students in undergraduate medical education. At the same time, it remains unknown how medical students use and incorporate practice questions and their rationales into their studies. To explore this heavily relied upon study strategy, semi-structured interviews were conducted with second-year medical students to assess how they approach using practice questions. Qualitative thematic analysis revealed several recurrent themes: (1) Medical students use practice questions for primary learning, (2) Medical students place more importance on the rationale of a practice question versus selecting the right answer, and (3) Medical students view practice questions as being designed to be used once or having a single-use. Together, these themes provide insight into how medical students use practice questions to study, which may guide medical educators in their creation of practice questions with appropriate rationales and provide foundational data for future mixed methods analyses seeking to generalize these findings.

Abstract NLRP3 inflammasome has been implicated in neutrophil polarization and extrusion of neutrophil extracellular traps (NETs) in vitro and facilitates secretion of Il1-beta (IL-1β). Permanent ligation of the left anterior descending artery was used to induce MI in WT and NLRP3−/− mice as well as in NLRP3−/− recipient mice transfused with either WT or NLRP3−/− neutrophils. NLRP3 deficiency reduced infarct size to roughly a third of WT heart injury and preserved left ventricular (LV) function at 12 h after MI as assessed by echocardiography and triphenyltetrazolium chloride staining of live tissue. Transfusion of WT but not NLRP3−/− neutrophils after MI increased infarct size in NLRP3−/− mice and significantly reduced LV function. The key features of myocardial tissue in WT neutrophil transfused recipients were increased H3Cit-positive deposits with NET-like morphology and increased tissue levels of IL-1β and plasma levels of von Willebrand Factor (VWF). Flow cytometry analysis also revealed that neutrophil NLRP3 increased the number of labeled and transfused neutrophils in the bone marrow of recipient mice following MI. Our data suggest a key role for neutrophil NLRP3 in the production of IL-1β and deposition of NETs in cardiac tissue exacerbating injury following MI. We provide evidence for a link between neutrophil NLRP3 and VWF release likely enhancing thromboinflammation in the heart. Neutrophil NLRP3 deficiency conferred similar cardioprotective effects to general NLRP3 deletion in MI rendering anti-neutrophil NLRP3 therapy a promising target for early cardioprotective treatment.

Abstract Safe and effective brain tumor surgery aims to remove tumor tissue, not non-tumoral brain. This is a challenge since tumor cells are often not visually distinguishable from peritumoral brain during surgery. To address this, we conducted a multicenter study testing whether the Sentry System could distinguish the three most common types of brain tumors from brain tissue in a label-free manner. The Sentry System is a new real time, in situ brain tumor detection device that merges Raman spectroscopy with machine learning tissue classifiers. Nine hundred and seventy-six in situ spectroscopy measurements and colocalized tissue specimens were acquired from 67 patients undergoing surgery for glioblastoma, brain metastases, or meningioma to assess tumor classification. The device achieved diagnostic accuracies of 91% for glioblastoma, 97% for brain metastases, and 96% for meningiomas. These data show that the Sentry System discriminated tumor containing tissue from non-tumoral brain in real time and prior to resection.

Abstract Maerl beds are listed as a priority marine feature in Scotland. They are noted for creating suitable benthic habitat for diverse communities of fauna and flora and in supporting a wide array of ecosystem services. Within the context of climate change, they are also recognised as a potential blue carbon habitat through sequestration of carbon in living biomass and underlying sediment. There are, however, significant data gaps on the potential of maerl carbon sequestration which impede inclusion in blue carbon policy frameworks. Key data gaps include sediment thickness, from which carbon content is extrapolated. There are additional logistical and financial barriers associated with quantification methods that aim to address these data gaps. This study investigates the use of sub-bottom profiling (SBP) to lessen financial and logistical constraints of maerl bed sediment thickness estimation and regional blue carbon quantification. SBP data were cross validated with cores, other SBP data on blue carbon sediments, and analysed with expert input. Combining SBP data with estimates of habitat health (as % cover) from drop-down video (DDV) data, and regional abiotic data, this study also elucidates links between abiotic and biotic factors in determining maerl habitat health and maerl sediment thickness through pathway analysis in structural equation modelling (SEM). SBP data were proved to be sufficiently robust for identification of maerl sediments when corroborated with core data. SBP and DDV data of maerl bed habitats in Orkney exhibited some positive correlations of sediment thickness with maerl % cover. The average maerl bed sediment thickness was 1.08 m across all ranges of habitat health. SEM analysis revealed maerl bed habitat health was strongly determined by abiotic factors. Maerl habitat health had a separate positive effect on maerl bed sediment thickness.

Abstract Health Canada (HC) has, since 2013, issued safety alerts restricting the use of codeine-containing drugs among breastfeeding women and children/adolescents under 18 years of age. These products are linked to breathing problems among ultra-rapid CYP2D6 metabolizers and early use of opioid can lead to future opioid misuse. Using a multi-province population-based cohort study, we estimate the impact of federal safety alerts on annual rates of codeine use in the Canadian pediatric population. We analyzed data from 8,156,948 children/adolescents in five Canadian provinces between 1996 and 2021, using a common protocol. Children/adolescents were categorized as: ≤ 12 years (children) or > 12 years (adolescents). We defined codeine exposure by ≥ 1 prescription filled for codeine alone or combined with other medications. For both age categories, we obtained province-specific codeine prescription filling rates per calendar year by dividing the number of children/adolescents with ≥ 1 codeine prescription filled by the number of person-time. Annual rates of codeine use per 1000 persons vary by province from 3.0 (Quebec) to 10.1 (Manitoba) in children, and from 5.5 to 51.3 in adolescents. After the 2013 HC advisory, exposure decreased in all provinces (adjusted level change from − 0.6 to − 18.4%) in children and from − 2.1 to − 17.9% in adolescents after the 2016 advisory. Annual rates declined over time in all provinces, following HC safety alerts specific to each of the two age categories.

Q fever is a zoonosis caused by Coxiella burnetii, primarily affecting those in close contact with domestic ruminants, the main source of human infection. Coxiella burnetii has also been detected in various wildlife species globally. In Australia, serological and molecular studies have shown exposure to and infection by C. burnetii in macropods, bandicoots, and koalas. However, the extent to which these species contribute to human infection remains unclear. An unpublished public health investigation into a Q fever case in a person involved in koala care could not conclusively link the infection to koalas due to the patient’s broad animal exposure. This study aimed to explore the potential role of koalas in transmitting C. burnetii to humans by investigating the presence of C. burnetii DNA in urogenital tract (UGT) swabs from koalas. DNA was extracted from UGT swabs from koalas in three regions in New South Wales, Australia. An optimised multiplex qPCR assay detected C. burnetii DNA in 2 out of 225 samples (0.89%) at approximately 10 genome equivalents per reaction. Both positive samples amplified all three gene targets. MLVA genotyping identified two distinct C. burnetii genotypes previously isolated from Australian Q fever cases. These findings highlight the need for vaccination against Q fever for those in close contact with koalas.

BackgroundAbortion has been legal for multiple indications in Ghana since 1985, and efforts have been made to expand the availability of safe abortion care in the years since. However clandestine, and potentially unsafe, abortions remain common, suggesting numerous barriers to access persist; one possible barrier is poor knowledge of the abortion law among those working in health facilities. Our study aimed to identify levels of legal knowledge among health facility staff across Ghana.MethodsData for this paper are drawn from a nationally representative cross-sectional health facility survey conducted in 2018; our analytic sample includes 340 facilities that provide induced abortion and/or postabortion care (PAC). The survey collected data on provision of abortion and PAC, as well as knowledge of abortion legality and recommendations for reducing unsafe abortion. We used descriptive statistics to examine levels of knowledge and recommendations, and logistic regression to assess associations with individual and facility characteristics.FindingsComprehensive knowledge of the legal indications for abortion was low among health facility staff; just 6% identified all legal indications, and the majority (83%) underestimated the number of conditions under which abortion is legal. Knowledge was higher for more restrictive indications, such as a woman's life being at risk, which was identified by 72% of respondents, than more broadly interpretable indications, such as mental health, identified by 29%. Respondents in facilities providing both induced abortion and PAC had better knowledge of several legal indications than those in facilities providing PAC only.ConclusionsHealth facility staff have significant gaps in their knowledge of abortion legality. Knowledge of the law among this population is highly important for ensuring that abortion care is made available to the fullest extent of the law. Efforts are needed to improve knowledge of the law among providers and facility staff, particularly for indications with broad interpretability.

Abstract Protein arginine deiminases (PAD) 4 is an enzyme that catalyzes citrullination of protein and its role in autoimmune diseases has been established through clinical genetics and gene knock out studies in mice. Further, studies with PAD4 – deficient mice have shown that PAD4 deficiency does not lead to increased infection or immune suppression, which makes PAD4 an attractive therapeutic target for auto-immune and inflammatory diseases. PAD4 has critical enzymatic role of promoting chromatin decondensation and neutrophil extracellular traps (NETs) formation that is associated with a number of immune-mediated pathological conditions. Here, we present a non-covalent PAD4 inhibitor JBI-589 with high PAD4 isoform selectivity and delineated its binding mode at 2.88 Å resolution by X-ray crystallography. We confirmed its effectiveness in inhibiting NET formation in vitro. Additionally, by using two mouse arthritis models for human rheumatoid arthritis (RA), the well-known disease associated with PAD4 clinically, we established its efficacy in vivo. These results suggest that JBI-589 would be beneficial for both PAD4 and NET-associated pathological conditions.

Abstract NLR family pyrin domain containing 3 (NLRP3) inflammasome mediates caspase-1-dependent processing of inflammatory cytokines such as IL-1β, an essential endothelial activator, and contributes to the pathology of inflammatory diseases. To evaluate the role of NLRP3 in neutrophils in endothelial activation, which is still elusive, we used the thioglycollate-induced peritonitis model characterized by an early neutrophil influx, on Nlrp3 −/− and Nlrp3 +/+ mice. Nlrp3 −/− mice recruited fewer neutrophils than Nlrp3 +/+ into the peritoneum and showed lower IL-1β in peritoneal lavage fluid. The higher production of IL-1β in Nlrp3 +/+ was neutrophil-dependent as neutrophil depletion prevented the IL-1β production. The Nlrp3 +/+ neutrophils collected from the peritoneal fluid formed significantly more filaments (specks) than Nlrp3 −/− neutrophils of ASC (apoptosis-associated speck-like protein containing a caspase activating and recruitment domain), a readout for inflammasome activation. Intravital microscopy revealed that leukocytes rolled significantly slower in Nlrp3 +/+ venules than in Nlrp3 −/− . Nlrp3 −/− endothelial cells isolated from mesenteric vessels demonstrated a lower percentage of P-selectin-positive cells with lower intensity of surface P-selectin expression than the Nlrp3 +/+ endothelial cells evaluated by flow cytometry. We conclude that neutrophils orchestrate acute thioglycollate-induced peritonitis by producing IL-1β in an NLRP3-dependent manner. This increases endothelial P-selectin expression and leukocyte transmigration.

Background Chief residents receive minimal formal training in preparation for their administrative responsibilities. There is a lack of professional development programs specifically designed for chief residents. Objective In 2015, Academic Life in Emergency Medicine designed and implemented an annual, year-long, training program and virtual community of practice for chief residents in emergency medicine (EM). This study describes the curriculum design process and reports measures of learner engagement during the first two cycles of the curriculum. Methods Kern's Six-Step Approach for curriculum development informed key decisions in the design and implementation of the Chief Resident Incubator. The resultant curriculum was created using constructivist social learning theory, with specific objectives that emphasized the needs for a virtual community of practice, longitudinal content delivery, mentorship for participants, and the facilitation of multicenter digital scholarship. The 12-month curriculum included 11 key administrative or professional development domains, delivered using a combination of digital communications platforms. Primary outcomes measures included markers of learner engagement with the online curriculum, recognized as modified Kirkpatrick Level One outcomes for digital learning. Results An average of 206 chief residents annually enrolled in the first two years of the curriculum, with an overall participation by 33% (75/227) of the allopathic EM residency programs in the United States (U.S.). There was a high level of learner engagement, with an average 13,414 messages posted per year. There were also 42 small group teaching sessions held online, which included 39 faculty and 149 chief residents. The monthly e-newsletter had a 50.7% open rate. Digital scholarship totaled 23 online publications in two years, with 67 chief resident co-authors and 21 faculty co-authors. Conclusions The Chief Resident Incubator is a virtual community of practice that provides longitudinal training and mentorship for EM chief residents. This incubator conceptual framework may be used to design similar professional development curricula across various health professions using an online digital platform.

Though previous work has examined infant attention across a variety of tasks, less is known about the individual saccades and fixations that make up each bout of attention, and how individual differences in saccade and fixation patterns (i.e., scanning efficiency) change with development, scene content and perceptual load. To address this, infants between the ages of 5 and 11 months were assessed longitudinally (Experiment 1) and cross-sectionally (Experiment 2). Scanning efficiency (fixation duration, saccade rate, saccade amplitude, and saccade velocity) was assessed while infants viewed six quasi-naturalistic scenes that varied in content (social or non-social) and scene complexity (3, 6 or 9 people/objects). Results from Experiment 1 revealed moderate to strong stability of individual differences in saccade rate, mean fixation duration, and saccade amplitude, and both experiments revealed 5-month-old infants to make larger, faster, and more frequent saccades than older infants. Scanning efficiency was assessed as the relation between fixation duration and saccade amplitude, and results revealed 11-month-olds to have high scanning efficiency across all scenes. However, scanning efficiency also varied with scene content, such that all infants showing higher scanning efficiency when viewing social scenes, and more complex scenes. These results suggest both developmental and stimulus-dependent changes in scanning efficiency, and further highlight the use of saccade and fixation metrics as a sensitive indicator of cognitive processing.

BackgroundGiven that pregnant women taking medications are excluded from clinical trials, real-world evidence is essential. We aimed to build a Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO) and compare frequency of prematurity, low-birth-weight (LBW), major malformations, multiplicity, and gestational medication use across four provinces.MethodsCAMCCO is a collaborative research infrastructure that uses real-world data from large provincial health care databases in Canada; developed with standardized methods to similarly construct population-based pregnancy/child cohorts with longitudinal follow-up by linking administrative/hospital/birth databases. CAMCCO also includes a common repository to i) share algorithms and case definitions based on diagnostic and procedural codes for research/training purpose, and ii) download aggregate data relevant to primary care providers, researchers, and decision makers. For this study, data from Quebec (1998-2015), Manitoba (1995-2019), Saskatchewan (1996-2020), and Alberta (2005-2018) are compared (Chi-square tests, p-values), and trends are calculated using Cochran-Armitage trend tests.ResultsAlmost two-thirds (61%) of women took medications during pregnancy, mostly antibiotics (26%), asthma drugs (8%), and antidepressants (4%). Differences in the prevalence of prematurity (5.9-6.8%), LBW (4.0-5.2%), and multiplicity (1.0-2.5%) were statistically significant between provinces (pInterpretationMedications are often used among Canadian pregnancies but adverse pregnancy outcomes vary across provinces. Digitized health data may help researchers and care providers understand the risk-benefit ratios related to gestational medication use, as well as province-specific trends.

BackgroundThe COVID-19 global pandemic pushed many rehabilitation practitioners to pivot their in-person practice to adopt telerehabilitation as their main method of delivery. In addition to documenting information on interventions used with clients, it is best practice for therapists to use reliable and validated outcome measures to inform their interventions. ObjectiveThrough this scoping review, we aim to identify (1) which outcomes are being used remotely to assess balance, mobility, and gait in patients with neurological conditions, and (2) what psychometric data (validity, reliability, etc.) for remotely administered outcomes are available. MethodsThree main concepts will be included in our search: (1) neurological conditions; (2) administration by telerehabilitation; and (3) outcome measures for balance, mobility, and gait. Studies reporting remote assessment of neurological conditions published since 1990 will be included. The database search will be completed in MEDLINE (Ovid), CINAHL, PubMed, PsycINFO, EMBASE, and Cochrane. Gray literature including dissertations, conference papers, and protocol papers will also be sourced. Two reviewers will independently screen each title and abstract using pre-established inclusion and exclusion criteria. Manuscripts that appear to meet the criteria will be subject to further review, and full-text extraction using a pre-piloted extraction sheet if all criteria are met. The data will be categorized by assessment types describing impairments (such as balance, strength, and mobility) or activity limitations or participation restriction (such as functional mobility, ambulatory functions, and activities of daily living). ResultsThis scoping review will document outcome measures currently used in the remote assessment of neurological conditions. To date, 235 titles and abstracts were screened. We are in the process of finalizing the full text screening for the inclusion of articles. We expect the full screening to be completed in November 2021 and data analysis in January 2022. Our results are expected to be published in early 2022. ConclusionsThe optimal use of telerehabilitation as a mode to deliver rehabilitation intervention should be coupled with the completion of validated outcome measures. Therefore, it is crucial to further our knowledge on remote outcome measures and therapeutic assessments. International Registered Report Identifier (IRRID)PRR1-10.2196/27186

BackgroundMedications already available to treat other conditions are presently being studied in clinical trials as potential treatments for COVID-19. Given that pregnant women are excluded from these trials, we aimed to investigate their safety when used during pregnancy within a unique population source.MethodsUsing the population-based Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn (1998-2015). Taking potential confounders into account including indications for use, the risk of prematurity, low birth weight (LBW), small for gestational age (SGA), and major congenital malformation (MCM) associated with COVID-19 repurposed drug use during pregnancy were quantified using generalized estimation equations.ResultsOf the 231,075 eligible pregnancies, 107 were exposed to dexamethasone (0.05%), 31 to interferons (0.01%), 1,398 to heparins (0.60%), 24 to angiotensin-receptor blockers (ARB) (0.01%), 182 to chloroquine (0.08%), 103 to hydroxychloroquine (0.05%), 6,206 to azithromycin (2.70%), 230 to oseltamivir (0.10%), and 114 to HIV medications (0.05%). Adjusting for potential confounders, we observed an increased risk of prematurity related to dexamethasone (aOR 1.92, 95%CI 1.11-3.33; 15 exposed cases), anti-thrombotics (aOR 1.58, 95%CI 1.31-1.91; 177 exposed cases), and HIV medications (aOR 2.04, 95%CI 1.01-4.11; 20 exposed cases) use. An increased risk for LBW associated with anti-thrombotics (aOR 1.72, 95%CI 1.41-2.11; 152 exposed cases), and HIV medications (aOR 2.48, 95%CI 1.25-4.90; 21 exposed cases) use were also found. Gestational exposure to anti-thrombotics (aOR 1.20, 95%CI 1.00-1.44; 176 exposed cases), and HIV medications (aOR 2.61, 95%CI 1.51-4.51; 30 exposed cases) were associated with SGA. First-trimester dexamethasone (aOR 1.66, 95%CI 1.02-2.69; 20 exposed cases) and azithromycin (aOR 1.10, 95%CI 1.02-1.19; 747 exposed cases) exposures were associated with MCM.ConclusionsMany available medications considered as treatments for COVID-19 are associated with adverse pregnancy outcomes. Caution is warranted when considering these medications during the gestational period.

Background: Point-of-care ultrasound (POCUS) has an emerging presence in medical student education; however, there is limited evidence that this translates into appropriate clinical care. We aimed to evaluate the ability of medical students to integrate newly obtained POCUS knowledge into simulated clinical cases. Methods: We conducted an observational study of medical students participating in a mandatory rotation during their clinical years. Students in small groups underwent formalized lung POCUS lectures and hands-on training. Students participated in simulated “dyspnea” cases focused on either congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD). They were observed for critical actions including elements related to medical decision-making and ultrasound use and interpretation. Ultrasound-specific written knowledge was gauged with a short assessment after the first lecture and at week 4. Results: A total of 62 students participated and were observed during simulations. All groups correctly identified and treated CHF in the simulated case. Most groups (7 out of 9) attempted to use ultrasound in the CHF case; five groups correctly recognized B-lines; and four groups correctly interpreted B-lines as pulmonary edema. No groups used ultrasound in the COPD case. Conclusion: Most students attempted to use ultrasound during simulated CHF cases after a brief didactic intervention; however, many students struggled with clinical application. Interestingly, no students recognized the need to apply ultrasound for diagnosis and management of COPD. Future studies are needed to better understand how to optimize teaching for medical students to improve translation into POCUS skills and improved clinical practice.

Objective Our study aims to understand the psychological impact of the COVID-19 pandemic among healthcare workers (HCWs) at acute hospital settings in the South-East of Ireland, as a crucial step in guiding policies and interventions to maintain their psychological well-being.Design Observational cohort study.Participants and setting 472 HCWs participated from two distinct acute hospital settings, A and B, in the South-East of Ireland.Primary and secondary outcome measures Measures of psychological distress—depression, anxiety, acute and post-traumatic stress disorder (PTSD)—as dictated by the Depression, Anxiety and Stress Scale (DASS-21) and Impact of Event Scale-Revised (IES-R). An independent sample t-test and a Mann-Whitney U test was used to determine significance of difference in continuous variables between groups. Categorical variables were assessed for significance with a χ2 test for independence.Results The DASS-21 provided independent measures of depression (mean 4.57, IQR 2–7), anxiety (mean 3.87, IQR 1–6) and stress (mean 7.41, IQR 4–10). Positive scores were reflected in 201 workers (42.6%) for depression and 213 (45.1%) for both anxiety and stress. The IES-R measured subjective distress on three subscales: intrusion (mean 1.085, IQR 0.375–1.72), avoidance (mean 1.008, IQR 0.375–1.5) and hyperarousal (mean 1.084, IQR 0.5–1.667). Overall, 195 cases (41.3%) were concerning for PTSD. Site B scored significantly higher across all parameters of depression (5.24 vs 4.08, p

The surge of coronavirus disease 2019 (COVID-19) research studies involving human participants in response to the pandemic has meant that research ethics committees across the world have been challenged to adapt their processes to meet demand while retaining high standards of review. Ethics review during this pandemic remains essential to ensure the safety, dignity and well-being of research participants, however research ethics committees are now faced with new, and often complex, ethics considerations and logistical challenges. This Open Letter looks specifically at the Irish experience of establishing a national approach to research ethics review amidst a global pandemic. This represents Ireland’s first National Research Ethics Committee, which provided the research community with an expedited and ‘single national opinion’ for ethics review for COVID-related research. The insights gleaned and lessons learned from the Irish experience may inform emergency responses to future pandemics or public health emergencies.

A ruptured sinus of Valsalva aneurysm as a cause of aorto–atrial fistula is very rare. We present the case of a 53-year-old female who presented with symptoms of acute heart failure and suspicion of an aorto–atrial fistula found on a transthoracic echocardiogram, which was confirmed on transesophageal echocardiography. A coronary angiogram showed normal coronary arteries but confirmed the right aorto–atrial fistula on aortogram. She underwent successful surgical repair of the fistula. Her postoperative echocardiogram showed a normal right atrium and right ventricle with no shunt. A ruptured sinus of Valsalva aneurysm is a devastating event and presents as acute heart failure. Prompt diagnosis and surgical repair is necessary to prevent mortality.

BACKGROUND:In Côte d'Ivoire, induced abortion is legally restricted unless a pregnancy threatens a woman's life. Yet the limited available evidence suggests abortion is common and that unsafe abortion is contributing to the country's high maternal mortality. Our study aimed to estimate the one-year incidence of induced abortion in Côte d'Ivoire using both direct and indirect methodologies, determine the safety of reported abortions, and identify the women most likely to experience a recent induced abortion or an unsafe abortion. METHODS:In 2018, we conducted a nationally representative, population-based survey of women age 15 to 49 in Côte d'Ivoire. Women reported their own abortion experiences and those of their closest female confidante. We estimated the one-year incidence of induced abortion, and the safety of the abortions women experienced. Using bivariate and multivariate regression, we separately assessed sociodemographic characteristics associated with having had a recent abortion or an unsafe abortion. RESULTS:Overall, 2,738 women participated in the survey, approximately two-thirds of whom reported on the abortion experiences of their closest female friend. Based on respondent data, the one-year incidence of induced abortion was 27.9 (95% CI 18.6-37.1) per 1,000 women of reproductive age, while the confidante incidence was higher at 40.7 (95% CI 33.3-48.1) per 1,000. Among respondents, 62.4% of abortions were most unsafe, while 78.5% of confidante abortions were most unsafe. Adolescents, less educated women, and the poorest women had the most unsafe abortions. CONCLUSION:This study provides the first national estimates of induced abortion incidence and safety in Côte d'Ivoire, using a population-based approach to explore social determinants of abortion and unsafe abortion. Consistent with other research, our results suggest that legal restrictions on abortion in Côte d'Ivoire are not preventing women from having abortions, but rather pushing women to use unsafe, potentially dangerous abortion methods. Efforts to reduce the harms of unsafe abortion are urgently needed.

Aryl hydrocarbon receptor (AHR) agonists such as dioxin have been associated with obesity and the development of diabetes. Whole-body Ahr knockout mice on high-fat diet (HFD) have been shown to resist obesity and hepatic steatosis. Tissue-specific knockout of Ahr in mature adipocytes via adiponectin-Cre exacerbates obesity while knockout in liver increases steatosis without having significant effects on obesity. Our previous studies demonstrated that treatment of subcutaneous preadipocytes with exogenous or endogenous AHR agonists disrupts maturation into functional adipocytes in vitro. Here, we used platelet-derived growth factor receptor alpha (Pdgfrα)-Cre mice, a Cre model previously established to knock out genes in preadipocyte lineages and other cell types, but not liver cells, to further define AHR's role in obesity. We demonstrate that Pdgfrα-Cre Ahr-floxed (Ahrfl/fl) knockout mice are protected from HFD-induced obesity compared to non-knockout Ahrfl/fl mice (control mice). The Pdgfrα-Cre Ahrfl/fl knockout mice were also protected from increased adiposity, enlargement of adipocyte size, and liver steatosis while on the HFD compared to control mice. On a regular control diet, knockout and non-knockout mice showed no differences in weight gain, indicating the protective phenotype arises only when animals are challenged by a HFD. At the cellular level, cultured cells from brown adipose tissue (BAT) of Pdgfrα-Cre Ahrfl/fl mice were more responsive than cells from controls to transcriptional activation of the thermogenic uncoupling protein 1 (Ucp1) gene by norepinephrine, suggesting an ability to burn more energy under certain conditions. Collectively, our results show that knockout of Ahr mediated by Pdgfrα-Cre is protective against diet-induced obesity and suggest a mechanism by which enhanced UCP1 activity within BAT might confer these effects.

Objectives The aim of this study was to determine the association between antidepressant (AD) classes, types and duration of use during pregnancy and the risk of gestational diabetes mellitus (GDM).Design and setting A nested case–control study was conducted within the Quebec Pregnancy Cohort (QPC), a Canadian provincial database which includes data on all pregnancies and children in Quebec from January 1998 to December 2015.Primary outcome measures Gestational diabetes mellitus.Participants Cases of GDM were identified after week 20 of pregnancy and randomly matched 1:10 to controls on gestational age at index date (ie, calendar date of GDM) and year of pregnancy. AD exposure was assessed by filled prescriptions between the beginning of pregnancy (first day of last menstrual period) and index date. Conditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR).Results Among 20 905 cases and 209 050 matched controls, 9741 (4.2%) women were exposed to ADs. When adjusting for potential confounders, AD use was associated with an increased risk of GDM (aOR 1.19, 95% CI 1.08 to 1.30); venlafaxine (aOR 1.27, 95% CI 1.09 to 1.49) and amitriptyline (aOR 1.52, 95% CI 1.25 to 1.84) were also associated with an increased risk of GDM. Moreover, the risk of GDM was increased with longer duration of AD use, specifically for serotonin norepinephrine reuptake inhibitors, tricyclic ADs and combined use of two AD classes. No statistically significant association was observed for selective serotonin reuptake inhibitors.Conclusion The findings suggest that ADs—and specifically venlafaxine and amitriptyline—were associated with an increased risk of GDM.

This paper reports the development and baseline data of a vignettes-based measure of gender equality. METHODS:Vignettes were developed through 3-day long focus groups. After piloting in 13 sites and repiloting a revised version in 6 countries, responses were categorized by the construct tapped and a scoring system developed. Finalized vignettes were then tested in DR Congo, Ecuador and China. RESULTS:Young adolescents can successfully respond to vignettes; and can differentiate self from hypothetical protagonists of same and opposite sex. Response differences by sex of respondent and protagonist were statistically significant across a range of scenarios and settings. CONCLUSION:This is the first vignettes-based measure for young adolescents assessing young adolescent perceptions of relationships differentiated by sex of the protagonist.

Acquisition of fresh water (FW) is problematic for FW-dependent animals living in marine environments that are distant from sources of FW associated with land. Knowledge of how marine vertebrates respond to oceanic rainfall, and indeed the drinking responses of vertebrates generally following drought, is extremely scant. The Yellow-bellied Sea Snake (Hydrophis platurus) is the only pelagic species of squamate reptile and ranges across the Indo-Pacific oceans, having one of the largest geographic distributions of any vertebrate species. It requires FW and dehydrates at sea during periods of drought. Here we report drinking behaviors of sea snakes precisely at the transition from dry to wet season when rainfall first impacted the ocean following 6 months of seasonal drought. We show that the percentage of sea snakes that voluntarily drank FW in the laboratory when captured over eight successive days decreased from 80% to 13% before and after rainfall commenced, respectively. The percentage of snakes that drank immediately following capture exhibited a significant linear decline as the earliest rains of the wet season continued. Drinking by snakes indicates thirst related to dehydration, and thus thirsty snakes must have dehydrated during the previous six months of drought. Hence, the progressive decline in percentage of thirsty snakes indicates they were drinking from FW lenses associated with the first rainfall events of the wet season. These data reinforce the importance of accessing oceanic FW from precipitation, with implications for survival and distribution of pelagic populations that might be subjected to intensifying drought related to climate change.

PurposeWe described the medication use during pregnancy in the French population using the French Pregnancy Cohort (FPC).MethodsThe FPC was built with the sampling of all pregnant women included in the French Echantillon généraliste des bénéficiaires (EGB), which is a 1/97th representative sample of the population covered by the French health insurance. The EGB includes anonymized information on the socio-demographic and medical characteristics of beneficiaries, and the health care services they have received such as diagnoses and procedure codes as well as data on filled reimbursed medication; EGB also includes data on hospital stays in all public and private French health facilities. Each filled prescription record contains information on drug brand and generic names, date of prescription and date of dispensing, quantity dispensed, mode of administration, duration of prescription, dosage, and prescribing physician specialty. FPC includes data on all pregnancies of women in the EGB (2010-2013). Date of entry in the FPC is the first day of pregnancy regardless of pregnancy outcome (spontaneous abortions or planned abortions (with or without medical reasons), deliveries), and data on women are collected retrospectively for a period of one year before pregnancy, and prospectively during pregnancy, and up to one year after delivery. The prevalence of prescribed medications before, during and after pregnancy was compared; comparison was also done between trimesters. Pregnancy outcomes are described and include spontaneous and planned abortions, livebirths, and stillbirths.ResultsFPC includes data on 36,065 pregnancies. Among them, 27,253 (75.6%) resulted in a delivery including 201 stillbirths (0.7%). The total number of spontaneous abortions was 6,718 (18.6%), and planned abortions 2,094 (5.8%). The prevalence of filled medication use was 91.1%, 89.9%, and 95.6% before, during and after pregnancy, respectively. Although there was a statistically significant decrease in the proportion of use once the pregnancy was diagnosed (first trimester exposure, 76.4% vs. exposure in the year prior to pregnancy, 91.1% (p < .01)), post-pregnancy medication use was above the pre-pregnancy level (95.6%). Maternal depression was the most prevalent comorbidity during pregnancy (20%), and post-partum depression was higher in those who delivered a stillborn infant (38.8%) as well as in those with a spontaneous (19.5%) or planned abortion (22.4%) compared to those with a liveborn (12.0%).ConclusionFPC is an excellent tool for the study of the risk and benefit of drug use during the perinatal period. FPC has the advantage of including a representative sample of French pregnant women, and study medications only available in France in addition to others available worldwide.

The overall survival for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) remains low, with little progress made over decades. Cisplatin, most frequently used for HNSCC treatment, activates mitochondria-dependent apoptosis through the BCL-2 family proteins. We have previously demonstrated that the pro-apoptotic BH3-only protein, NOXA plays a critical role in this process. NOXA binds and inactivates anti-apoptotic MCL-1, while the BCL-2 inhibitor ABT-263 is capable of inactivating anti-apoptotic BCL-2 and BCL-XL. We hypothesized that combination of NOXA and ABT-263 treatment increases cell death by simultaneously inhibiting anti-apoptotic BCL-2 family proteins in HNSCC cells. Here, we demonstrated that combination of ectopic NOXA expression and ABT-263 enhanced apoptosis in p53-inactive, p53 wild-type, and human papillomavirus (HPV)-positive HNSCC cell lines. Furthermore, a retinoid derivative and an endoplasmic reticulum stress inducer, fenretinide, induced NOXA, and combination of fenretinide and ABT-263 strongly induced apoptosis in HNSCC cells regardless of the HPV or p53 statuses. We also found that MCL-1 and BCL-XL are the primary targets of apoptosis induced by the combinations. These results will develop novel and alternative therapeutic strategies to directly modify the cell death machinery in HNSCC.

Rickettsioses are arthropod-borne zoonotic diseases, several of which occur in Australia. This study aimed to assess the exposure levels and risk factors for Rickettsia spp. among Australian wildlife rehabilitators (AWRs) using serology, PCR and a questionnaire. Antibody titres against Spotted Fever Group (SFG), Typhus Group (TG) and Scrub Typhus Group (STG) antigens were determined using an immunofluorescence assay. PCR targeting the gltA gene was performed on DNA extracts from whole blood and serum. Logistic regression was used to identify risk factors associated with seropositivity. Of the 27 (22.1%; 27/122) seropositive participants all were seropositive for SFG, with 5/27 (4.1%) also positive for TG. Of the 27 positive sera, 14.8% (4/27) were further classified as exposure to R. australis, 3.7% (1/27) to R. honei, 3.7% (1/27) to R. felis and 77.8% (21/27) were classified as ‘indeterminate’—most of which (85.7%; 18/21) were indeterminate R. australis/R. honei exposures. Rickettsia DNA was not detected in whole blood or serum. Rehabilitators were more likely to be seropositive if more than one household member rehabilitated wildlife, were older than 50 years or had occupational animal contact. These findings suggest that AWRs are at increased risk of contracting Rickettsia-related illnesses, however the source of the increased seropositivity remains unclear.