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The objective of this research was to evaluate the potential economic and environmental effects of the formulation model used to balance dairy rations for metabolizable protein (MP) or 3 essential AA (EAA: His, Lys, and Met) in 3 regions of Canada with different farming systems. The Maritimes, Central Canada, and the Prairies reference dairy farms averaged 63, 71, 144 mature cows per herd and 135, 95, 255 ha of land, respectively. Using N-CyCLES, a whole-farm linear program model, dairy rations were balanced for (1) MP, based on National Research Council (NRC) requirements (MP_2001); (2) MP plus Lys and Met, based on NRC (AA_2001); (3) MP (MP_Rev); or (4) for His, Lys, and Met (AA_Rev), both based on a revised factorial approach revisiting both supply and requirements of MP and EAA. Energy was balanced to meet requirements based on NRC (2001). Assuming the requirements were met within each approach, it was considered that milk yield and composition were not affected by the type of formulation. Given the assumptions of the study, when compared with MP_2001 formulation, balancing dairy rations using the AA_Rev approach reduced calculated farm N balance by 3.8%, on average from 12.71 to 12.24 g/kg of fat- and protein-corrected milk; it also enhanced farm net income by 4.5%, from 19.00 to 19.70 $CAN/100 kg of fat- and protein-corrected milk, by reducing inclusion of protein concentrate in dairy rations. Calculated animal N efficiency was on average 4.3% higher with AA_Rev than with MP_2001 for mid-lactation cows. This gain in N efficiency would result in a reduction in N2O emission by manure, contributing to a partial decrease of total greenhouse gas emission by 1.7%, through a reduction of N excreted in manure. With the AA_2001 formulation, farm N balance was 1% higher than with MP_2001 formulation while reducing farm net income by 6.4%, due to the need to purchase rumen-protected AA, with no effect on total greenhouse gas emission. Both MP formulations lead to fairly similar outputs. The AA_Rev formulation also indicated that His might be a co-limiting AA with Met in dairy rations balanced with ingredients usually included in Canadian dairy rations. Given the assumptions of the study, balancing dairy rations for 3 EAA (His, Lys, and Met) rather than MP, has some potential positive effects on Canadian dairy farms by increasing net incomes through a reduction of crude protein supply, leading to a decreased environmental effect.

Intersectionality, a theory for understanding women's health issue. Intersectionality offers the possibility of holistic analyzes to understand and act on women's health issue. It facilitates the exploration of the different dimensions of social inequalities in health, which are both at the level of institutions and of the individual experiences of people who live at the intersection of multiple dimensions of domination and power.

Studies of reach control with the body stationary have shown that proprioceptive and visual feedback signals contributing to rapid corrections during reaching are processed by neural circuits that incorporate knowledge about the physical properties of the limb (an internal model). However, among the most common spatial and mechanical perturbations to the limb are those caused by our body's own motion, suggesting that processing of vestibular signals for online reach control may reflect a similar level of sophistication. We investigated this hypothesis using galvanic vestibular stimulation (GVS) to selectively activate the vestibular sensors, simulating body rotation, as human subjects reached to remembered targets in different directions (forward, leftward, rightward). If vestibular signals contribute to purely kinematic/spatial corrections for body motion, GVS should evoke reach trajectory deviations of similar size in all directions. In contrast, biomechanical modeling predicts that if vestibular processing for online reach control takes into account knowledge of the physical properties of the limb and the forces applied on it by body motion, then GVS should evoke trajectory deviations that are significantly larger during forward and leftward reaches as compared with rightward reaches. When GVS was applied during reaching, the observed deviations were on average consistent with this prediction. In contrast, when GVS was instead applied before reaching, evoked deviations were similar across directions, as predicted for a purely spatial correction mechanism. These results suggest that vestibular signals, like proprioceptive and visual feedback, are processed for online reach control via sophisticated neural mechanisms that incorporate knowledge of limb biomechanics.

Two His deletion studies were conducted to examine the mechanisms used by dairy cows to support milk true protein yield (MTPY) when His supply is altered. The potential mechanisms involved in how the efficiency of utilization of His varied included reduced catabolism, more efficient mammary usage, and use of His labile pools. For the first study, 5 multicatheterized cows were used in a 4 × 4 Latin square plus 1 cow with 14-d periods. Treatments were abomasal infusion of increasing doses of His (0, 7.6, 15.2, and 20.8 g/d) in addition to a mixture of AA (595 g/d; casein profile excluding His). Cows were fed the same protein-deficient diet throughout the study. The MTPY increased linearly with a quadratic tendency with increasing doses of His. Muscle concentrations of carnosine, a His-based dipeptide, tended to increase in a quadratic manner with increasing His supply, suggesting that the 0- and 7.6-g doses were insufficient to cover His requirement. Liver catabolism of His decreased as His supply decreased. Mammary fractional removal of His was considerably greater at low His supply, but the ratio of His mammary net uptake to milk output was not affected by the rate of His infusion, averaging 1.02. The mechanisms to face a reduced His supply included reduced His hepatic catabolism, more efficient His mammary use of lowered arterial supply, and, to a lesser extent, use of His labile pools. Two independent estimates of His efficiency were calculated, one based on the sum of exported proteins (measured MTPY plus estimated metabolic fecal protein and scurf; i.e., the anabolic component, EffMTPY) and the other based on liver removal (i.e., the catabolic component). These 2 estimates followed the same pattern of response to His supply, decreasing with increasing His supply. The EffMTPY at which MTPY peaked was 0.785. For the second study, 6 cows were used in a 6 × 6 Latin square with 7-d periods. Two greater doses of His (30.4 and 38.0 g/d) were added; otherwise, the nutritional design was similar to the first study. In this second study, the indicator AA oxidation technique was used instead of the multiorgan approach, with labeled Leu as the indicator of His utilization. The MTPY peaked and Leu oxidation reached the nadir at an average EffMTPY of 0.763. Combined across both studies, the data indicate that optimal usage of His would occur at a threshold EffMTPY of 0.77. The agreement between experimental approaches across both studies indicates that the biological optimal supply of His expressed in grams per day could be calculated as the sum of exported proteins divided by this EffMTPY plus estimated endogenous urinary excretion.

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

Objective: To estimate, among people with multiple sclerosis, the extent to which a personally tailored exercise programme (MSTEP©) resulted in greater improvements in exercise capacity and related outcomes over 12 months in comparison with general exercise guidelines. Design: Two-group randomized trial. Subjects: Ambulatory and sedentary. Interventions: MSTEP©, a personally adapted exercise regimen done on most days including two days of high intensity exercise; guidelines recommending 30 minutes of moderate intensity aerobic and strength training two times per week. Main measures: Primary outcome was peak oxygen consumption (VO2peak) at 12 months; secondary outcomes were composite measures of physical function, fatigue, and health-related quality of life. Results: In total, 137 people were randomized, 66 were lost over 12 months leaving 71 with outcome data, 34 in MSTEP© group, and 37 in the Guideline group. Exercise enjoyment and confidence and exercise-induced fatigue predicted retention. There were no differences between groups on the proportion making a 10% increase in VO2peak (27.1% MSTEP© vs 29.6% Guidelines; OR: 0.83; 95% CI: 0.23–3.08) by the 12 month assessment. The effect on fatigue was larger in the MSTEP© group than the Guideline groups (OR: 1.59; 95% CI: 0.93–2.74), the effect on physical function was more modest (OR: 1.35; 95% CI: 0.80–2.25), and null for health-related quality of life outcomes. Conclusions: The disappointing exercise retention suggests that people with multiple sclerosis may not consider exercise important to their brain health. Either type of exercise resulted in stable exercise capacity over 1 year in those sticking with the programme.

Background: Chronic pain after moderate-to-severe traumatic brain injury (TBI) is associated with notable sensory alterations. Although the incidence of TBI is rapidly growing in older populations, elderly individuals have been largely excluded from sensory testing studies, thus limiting evidence regarding the influence of age on pain-related sensory alterations after TBI. This study aimed to investigate the effect of age on the sensory profiles of patients with and without chronic pain after moderate-to-severe TBI. Methods: Thermal and mechanical quantitative sensory testing were performed on the painful and contralateral body regions in TBI participants with pain (TBI-P) and on both forearms in TBI participants without pain (TBI-NP). Descriptive information about chronic pain and psychological comorbidities was assessed using validated questionnaires. Results: Participants included 37 young (18–59 years, 57% with chronic pain) and 22 elderly (≥60 years, 46% with chronic pain) survivors of moderate-to-severe TBI. TBI-P participants exhibited significant alterations in heat and pressure pain sensitivity compared to TBI-NP participants, with more pronounced decreases in heat detection in the elderly group and increased warmth sensitivity in the young group. Alterations were not always associated with chronic pain, as cold hypoesthesia was found in elderly TBI-NP participants. In both age groups, chronic pain was associated with higher levels of depressive mood. Conclusions: Results suggest that young and elderly TBI survivors have both common and unique sensory properties, highlighting the need to pursue sensory testing studies in older patient groups. Depression might also be an important target for pain management after TBI.

Objectives Growing evidence points to underlying sex differences in the risk factors and clinical presentation of dementia. It is unclear, however, whether sex differences also exist in the management and healthcare utilization of persons with dementia. We compared primary care performance and health service use indicators for newly identified men and women with dementia in Ontario, Canada, over a 12-year period. Design Population-based, repeated cohort study between 2002 and 2014. Setting Ontario, Canada. Participants A total of 318 350 community-dwelling adults, aged 65 years and older, newly identified with dementia, followed for up to 1 year. Measurements Eighteen indicators of primary care performance and health service use were assessed. Results Approximately 60% of the study population were women. Few differences in the indicators were observed between sexes, although men had fewer diagnoses first recorded by the family physician, more visits to noncognition specialists, less use of home care, more hospitalizations and readmissions, and longer discharge delays. Most indicators remained relatively stable over time for both men (median relative change = 13.7%; interquartile range [IQR] = 4.5%-29.7%) and women (median relative change = 15.7%; IQR = 5.9%-31.5%). Notable improvements over time for both sexes included access to an interprofessional primary care team, use of home care, and decreased use of long-term care. Areas of worsening included a higher occurrence of emergency department visits, lower continuity of care, and longer discharge delays. Conclusion These findings raise awareness on the similarities and differences in management and health system use for men and women newly diagnosed with dementia, particularly the imbalance in hospital and home care use. As health systems continue to adapt to meet the needs of the growing dementia population, policy makers and clinicians should be mindful to develop care plans and interventions that consider the influence of sex on the need for services. J Am Geriatr Soc 68:1056-1063, 2020.

New lineages of SARS-CoV-2 are of potential concern due to higher transmissibility, risk of severe outcomes, and/or escape from neutralizing antibodies. Lineage B.1.1.7 (the Alpha variant) became dominant in early 2021, but the association between transmissibility and risk factors, such as age of primary case and viral load remains poorly understood. Here, we used comprehensive administrative data from Denmark, comprising the full population (January 11 to February 7, 2021), to estimate household transmissibility. This study included 5,241 households with primary cases; 808 were infected with lineage B.1.1.7 and 4,433 with other lineages. Here, we report an attack rate of 38% in households with a primary case infected with B.1.1.7 and 27% in households with other lineages. Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5–1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age and viral load., Establishing the relative transmissibility of emerging variants of SARS-CoV-2 is key for pandemic management. Here, the authors use full-population administrative data from Denmark linked to PCR test results and estimate that the Alpha variant was ~60% higher than other strains circulating in early 2021.

Biotin (B

To explore the knowledge content and structure of nursing students' decision-making in a high-stake clinical situation of postpartum hemorrhage using the Recognition-Primed Decision Model.According to research on clinical judgment, a nurse's expectations for a patient situation are central to the clinical decision-making process. However, little research has addressed the expectation concept and its relationship with the nurse's knowledge. Grounded in the naturalistic decision-making paradigm, the Recognition-Primed Decision Model provides a potential framework to describe the content and structure of nurses' knowledge and expectations as they unfold in high-stake clinical situations, such as postpartum hemorrhage. As it is typically used in studies of expert decision-making, it is crucial to test the adequacy of the Model with a student population and refine the research methods for using this framework.Descriptive design where qualitative data were analyzed using qualitative and quantitative methods.A convenience sample of 53 students enrolled in a maternal and child health course in the Fall of 2021 was formed. As part of an online exercise to prepare for a simulation, they read a vignette presenting the story of a woman experiencing postpartum hemorrhage and recorded their answers to questions designed to probe their decision-making. Recordings were transcribed and subjected to content analysis based on the four components of recognition according to the Recognition-Primed Decision Model (i.e., cues, expectations, goals and actions).All participants recognized the postpartum hemorrhage. Their knowledge was organized into clusters representing the potential causes (i.e., tone, trauma, tissue and thrombin) and consequences (i.e., hemodynamic instability) of postpartum hemorrhage, as well as other potential issues (e.g., pain and comfort, baby and partner, infection). Although students could identify relevant cues and actions, they had difficulties articulating their longer-term goals and expectations for the mother and care outcomes.This study showed the potential of the Recognition-Primed Decision Model to organize the content and structure of the knowledge that supported nursing students' decision-making in a high-stake situation. The findings suggest that their knowledge disproportionately focuses on the cause-and-effect relations between cues and actions. They invite further consideration of longer-term goals and expectations in nursing education to prepare students to anticipate events and assess patient responses appropriately.

The endocytic adaptor protein Numb acts as a tumor suppressor through downregulation of oncogenic pathways in multiple cancer types. The identification of splicing alterations giving rise to changes in Numb protein isoform expression indicate that Numb also has tumor promoting activity, though the underlying mechanisms are unknown. Here we report that NUMB exon 9 inclusion, which results in production of a protein isoform with an additional 49 amino acids, is a feature of multiple cancer types including all subtypes of breast cancer and correlates with worse progression-free survival. Specific deletion of exon 9-included Numb isoforms (Exon9in) from breast cancer cells reduced cell growth and prevents spontaneous lung metastasis in a mouse model. Quantitative proteome profiling showed that loss of Exon9in causes downregulation of membrane receptors and adhesion molecules, as well as proteins involved in extracellular matrix organization and the epithelial-mesenchymal transition (EMT) state. In addition, exon 9 deletion caused remodeling of the endocytic network, decreased ITGβ5 surface localization, cell spreading on vitronectin and downstream signaling to ERK and SRC. Together these observations suggest that Exon9in isoform expression disrupts the endocytic trafficking functions of Numb, resulting in increased surface expression of ITGβ5 as well as other plasma membrane proteins to promote cell adhesion, EMT, and tumor metastasis.

Feed evaluation models (FEM) are a core part in dairy cow feeding. As these models are developed using different biological and mathematical approaches mainly tested in a research context, their abilities to predict production in commercial farms need to be validated, even more so when they are used outside the context of their development. Four FEM-National Research Council, 2001 (NRC_2001); Cornell Net Carbohydrate and Protein System, 2015 (CNCPS); NorFor, 2011; and INRA, 2018 (INRA_2018)-were evaluated on their abilities to predict daily milk protein yield (MPY) of 541 cows from 23 dairy herds in the province of Québec, Canada. The effects of cow and diet characteristics were tested on the residuals of MPY. Sensitivity and uncertainty analyses were then performed to evaluate the influence of the uncertainty of the main characteristics of cows and feed ingredients measured on the farm and used in the 4 FEM on the predictions of metabolizable protein (MP) supply and MPY. The 4 models had acceptable predictions of MPY, with concordance correlation coefficients (CCC) ranging from 0.75 to 0.82 and total bias ranging from 12.8% to 19.3% of the observed mean. The Scandinavian model NorFor had the best predictions with a CCC of 0.82, whereas the 3 other models had similar CCC at 0.75 to 0.76. The INRA_2018 and NRC_2001 models presented strong central tendency biases. Removing herd effect put the 4 FEM at the same level of performance, with 11.9 to 12.4% error. Analyzing model behavior within a herd seems to partly negate the effect of using predicted dry matter intake (DMI) in the comparison of models. Diet energy density, days in milk, and MPY estimated breeding value were related to the residual in the 4 models, and Lys and Met (as percent of MP) only in NRC_2001 and NorFor. This suggests that inclusion of these factors in these models would improve MPY predictions. From the sensitivity analysis, for the 4 FEM, DMI and factors affecting its prediction had the greatest influence on the predictions of MP supply and MPY. Of the feed ingredients, forage composition had the greatest effect on these predictions, including a strong effect of legume proportion with NorFor. Diet acid detergent fiber concentration had a very strong effect on MP supply and MPY predictions only in INRA_2018, because of its effect on organic matter digestibility estimation. The range of predictions of MP supply and MPY when combining all these potential uncertainties varied depending on the models. The INRA_2018 model presented the lowest standard deviation (SD) and NorFor the highest SD for the predictions of both MP supply and MPY. Overall, despite the fact that FEM were developed in a research context, their use in a commercial context yields acceptable predictions, with NorFor yielding the best predictions overall, although within-herd responses varied similarly for the 4 tested models.

Allogeneic hematopoietic cell transplantation (AHCT) represents the only curative therapy for many hematological malignancies. The graft versus leukemia effect, driven by donor T cells, plays a major role in its curative potential. This effect is sometimes very evident when patients with acute myeloid leukemia and myelodysplasia relapse after AHCT and are treated with donor lymphocyte infusions (DLIs). We retrospectively reviewed the charts of 64 patients who received DLI between 2012 and 2017 in our center. The mean age of the patients was 59 years (range, 34-79). Fifty percent were male (n = 32). The mean follow-up time after AHCT was 50.17 months (range, 8-174). The indication for DLI were disease progression, mixed chimerism, minimal residual disease, and other etiologies in 43.8%, 40.7%, 14%, and 1.5% of patients, respectively. The most common diagnosis was acute leukemia, followed by multiple myeloma. Of all patients, 59.4% received a transplant from a related donor, 39% received a transplant from an unrelated donor, and 1.6% received a transplant from a haploidentical donor. Reduced-intensity conditioning AHCT was the most frequent regimen used (53%). DLI was given alone in 79.7% of patients. Prophylactic DLI was given at 30 days after transplantation in patients who received human leukocyte antigen (HLA)-matched related human stem cell transplantation (HSCT) or 45 to 60 days post-transplant in patients receiving haploidentical HSCT or HLA-matched unrelated HSCT. Patients were treated without graft versus host disease (GVHD) prophylaxis. The use of DLI after transplantation remains a feasible procedure with rates of response60%. Moreover, DLIs are well tolerated with a GVHD rate 10% in our series. We can hypothesize that in our experience the efficacy of this strategy does not rely on the induction of GVHD.

Strategies that can improve health and maximize growth in the preweaning period should improve the subsequent production and longevity of replacement animals. Few data are available that quantify feed and water consumption, as well as growth, in healthy versus non-healthy calves—the objective of this study. A database of Holstein calves (2 for ≥3 consecutive days over the first 21 d of each experiment were retrospectively classified as diarrheic (DIA; n = 96); the remainder were classified as healthy (HEA; n = 217). Other health issues were minimal. The likelihood of elevated fecal score occurrence and the cumulative number of days with an elevated score were greater for DIA calves than for HEA calves. The initial total protein concentration in blood did not differ between classifications. Cumulative milk replacer dry matter intake (DMI) and water consumed from milk replacer were significantly less for DIA calves than for HEA calves, because DIA calves were more likely to refuse milk replacer. Cumulative starter DMI was decreased for DIA versus HEA calves. As a result, cumulative total DMI was significantly less for DIA calves than for HEA calves. Cumulative free water intake did not differ between classifications. The DIA calves were more likely to receive electrolyte solution and have more days given electrolyte solution than HEA calves. As a result, total cumulative intake of electrolyte solution was greater in DIA calves than in HEA calves. Cumulative total water intake did not differ between classifications. Initial BW did not differ between classifications; however, a classification × time interaction for BW indicated that HEA calves were heavier than DIA calves and had greater ADG. Significant classification × time interactions for hip height and heart girth revealed that HEA calves had a larger frame size. Gain–feed ratios for both milk replacer intake and total DMI differed between classifications: DIA calves were less feed-efficient than HEA calves. In conclusion, diarrhea in young calves decreases DMI, BW gain, and feed efficiency relative to HEA calves within 21 d of arrival.

Introduction While recent reports underscore the significance of the gut microbiome (GM) in health and disease, its importance in burn outcomes remains unclear. Moreover, aggressive intravenous (IV) fluid resuscitation of patients may alter intestinal flora. Herein, we describe GM changes following a large burn in swine randomized to different volumes of IV Lactated Ringers' (LR). Methods Anesthetized Yorkshire swine sustained 40% Total body surface area full-thickness burns and were randomized to different volumes of IV LR: none (n = 3), 15 mL/kg/day (Low; n = 6), or 80 mL/kg/day (High; n = 6). At baseline and days 1 and 2, fecal swabs were collected for 16 s rDNA sequencing. Proximal jejunum was collected immediately after euthanasia (day 2) for western blot, histopathology, and cytokine analyses. Results Burns produced significant shifts in β-diversity and non-significant reductions in α-diversity that did not recover regardless of treatment group. Burn-induced increases in Proteobacteria and decreases in Firmicutes were attenuated by IV fluids in a dose-dependent manner, and also correlated with α-diversity. IV fluids caused a dose-dependent increase in Bacteroides and prevented a transient increase in the opportunistic pathogen Haemophilus parainfluenzae. While high volumes of IV fluids increased intestinal Hsp70 levels (p = 0.0464), they reduced SGLT1 (p = 0.0213) and caspase3 (p = 0.0139) levels. IV fluids elicited a non-specific cytokine response however Bacteroidetes levels correlated with intestinal IL18 levels (p = 0.0166, R = 0.4201). Conclusions We present the first report on the gut microbiome in a porcine burn model, and present data to suggest that IV fluids may influence GM and gut functional proteins following a burn. Overall, burn injury results GM diversity shifts, which may expose diagnostic and/or therapeutic targets to improve outcomes.

Objectives: When the need for relatedness is frustrated, some older adults feel that life is not worth living and wish for death (WD). The aim of this study was to look at the perception of social ...

Item does not contain fulltext Across industrialized nations, children and teens are a highly prized target for the advertising industry because young people have a tremendous influence on family purchases; however, media scholars have long suggested that young people are a fundamentally vulnerable audience because they lack the necessary developmental competencies to adequately process and protect themselves from advertising communications. Yet, the precise developmental mechanisms have not been clearly articulated nor is there a clear understanding of how these competencies extend across childhood contexts (e.g., developmental phase, cultures). The current study seeks to lend clarity to this matter by looking at the potential influence that children's executive function and emotion regulation have on the relationship between television exposure (as a proxy of exposure to advertising messages and other consumption-oriented media content) and consumer behavior across a broad range of ages from two wealthy industrialized countries. Mothers of young elementary school children (5-8 years) and early adolescents (9-12 years) in the Netherlands (N = 333, 51.7% female child) and the United States of America (N = 810, 49.6% female child) took part in an online survey to report on their child's cognitive/affective development, media use, and consumer behavior (i.e., purchase requests, purchase related conflict). The results showed that across ages, executive function via attentional shifting moderated the link between purchase requests and purchase conflict, whereas positively valenced emotion regulation moderated the same relationship but only for older children. Lastly, the findings revealed that while there are differences in reported behavior among children in these two countries, the developmental processes tend to work in the same manner. The discussion focuses on what these findings mean for children's consumer development as they approach adolescence and how researchers and child advocates should take these developmental factors into account when considering children's potential vulnerability as consumers. 25 p.

Background Although depression has been extensively studied in relations to Intimate Partner Violence (IPV) and Childhood Maltreatment (CM), we still know little about its relationship with other types of violent crimes (e.g., physical assault, mugging) or how symptoms evolve over time. Methods Using a clinical sample of 132 crime victims, this study sought to map out group-based symptoms trajectories using Latent Growth Curve Analysis (LCGA) over the course of one year. Results Less than one month after having been assaulted, 30% of the sample reached the severe depression threshold. Symptoms tended to improve over time, with only 8% of participants reporting severe depression one year later. Analyses indicate the presence of three distinct profiles: one marked by severe and stable symptomatology over time (17%), the second characterized by a moderate level of symptoms that decreases exponentially over time (57%) and a third one describing a pattern of minimal depression throughout the year. People who suffered from persistent depression reported significantly lower levels of social support, scored higher on the ASDI and were also more likely to report some type of maltreatment in childhood but not IPV in adulthood, and appeared non-responsive to treatment. Limitations Results must be nuanced by the size (i.e., LCGA requirements and attrition) and nature of the sample (i.e., help-seeking victims only). Conclusions Although violence is a risk factor for depression, some individuals, especially those with a history of CM, appear to be more vulnerable to severe, persistent and treatment-resistant depression than others.

This study evaluated the concordance of Architect™ chemiluminescent microparticle immunoassays with Captia™ ELISA for cytomegalovirus (CMV) IgM and IgG, with Enzygnost™ and Captia™ ELISA for rubella IgM and IgG and with Trep-Sure™ ELISA for syphilis treponemal antibodies in a mixed pediatric and obstetrical population. Total agreement between assays and Kappa statistic value were 82.5% (95% CI: 75.6-87.7) and 0.65 (95% CI: 0.54-0.77) for CMV IgM, 82.8% (95% CI: 76.7-87.6) and 0.65 (95% CI: 0.55-0.75) for CMV IgG, 89.2% (95% CI: 82.9-93.4) and 0.56 (95% CI: 0.36-0.75) for rubella IgM, 88.6% (95% CI: 82.9-92.6) and 0.74 (95% CI: 0.63-0.84) for rubella IgG, and 97.9% (95% CI: 94.5-99.4) and 0.89 (95% CI: 0.79-1.00) for syphilis treponemal antibodies. This study demonstrates that the Architect™ chemiluminescent microparticle immunoassays correlate well with other FDA-approved ELISA assays in this specific population.

Background: Central pain associated with changes in sensory thresholds is one of the most enduring consequences of major trauma. Yet it remains sparsely studied among community-dwelling survivors of moderate-to-severe traumatic brain injury (TBI). Purpose: To describe and compare thermal and mechanical sensory thresholds in home-based patients with and without central pain after moderate-to-severe TBI with a cohort of healthy controls. Design: Cross-sectional. Method: Thresholds for cold/heat detection, thermal pain, touch, and distorted sensation were gathered using quantitative sensory testing (QST). QST was performed on the painful and contralateral pain-free body regions in TBI participants with pain (TBI-P) and on both forearms in TBI participants without pain (TBI-NP) and healthy controls (HC). Central pain was characterized using the Brief Pain Inventory–Short Form. Results: We tested 16 TBI-P patients, 17 TBI-NP patients, and 16 HC. Mean time since injury for TBI patients was 24 ± 15 months. TBI-P and TBI-NP patients showed significant loss in innocuous mechanical sensitivity compared to HC ( F = 18.929; Bonferroni-adjusted p ≤ .001). Right–left differences in cold pain sensations were significantly larger in TBI-P than in TBI-NP and HC participants ( F = 14.352; Bonferroni-adjusted p ≤ .001). Elevated heat sensitivity thresholds were also observed in TBI-P participants but remained within normal range. Conclusion: Damage to cutaneous mechanoreceptors is a necessary, but not sufficient, condition for the development of chronic central pain following TBI. Damage or incomplete recovery of cutaneous thermoreceptors may be a contributing factor to chronic pain after TBI.

Many problematic outcomes in agricultural and food systems have important dynamic dimensions and arise due to underlying system structure. Thus, understanding the linkages between system structure and dynamic behavior often is important for the design and implementation of interventions to achieve sustained improvements. System dynamics (SD) modeling represents system structure using stock-flow-feedback structures expressed as systems of differential equations solved by numerical integration methods. System dynamics methods also encompass a broader methodological approach that emphasizes model structural development and data inputs to replicate one of a limited number of problematic behavioral modes, anticipates dynamic complexity, and focuses on feedback processes arising from endogenous system elements. This paper highlights the process of SD modeling using 2 examples from animal agriculture at different scales. A dynamic version of the Cornell Net Carbohydrate and Protein System (CNCPS) that represents outcomes for an individual dairy cow is formulated as an SD model illustrates the benefits of the SD approach in modeling rumen fill and animal performance. At a very different scale, an SD model of the Brazilian dairy supply chain (farms, processing, and consumers) illustrates the country-level impacts of efforts to improve cow productivity and how impacts differ if productivity improvement occurs on small farms rather than large farms. The paper concludes with recommendations about how to increase awareness and training in SD methods to enhance their appropriate use in research and instruction.

Evaluate non-invasive vascular elastography (NIVE) in detecting vascular changes associated with obese children. Case-control study to evaluate NIVE in 120 children, 60 with elevated body mass index (BMI) (≥ 85th percentile for age and sex). Participants were randomly selected from a longitudinal cohort, evaluating consequences of obesity in healthy children with one obese parent. Radiofrequency ultrasound videos of the common carotid artery were obtained. The carotid wall was segmented and NIVE applied to measure cumulated axial strain (CAS), cumulated axial translation (CAT), cumulated lateral translation (CLT), maximal shear strain (Max |SSE|), and intima-media thickness (IMT). Multivariate analyses were used controlling for age, sex, Tanner stage, blood pressure, and low-density lipoprotein. Statistical significance was set to 0.05–0.008. Participants were 10–13 years old (mean 11.4 and 12.0, for normal and elevated BMI groups, p

Alfalfa has a lower fiber digestibility and a greater concentration of degradable protein than grasses. Dairy cows could benefit from an increased digestibility of alfalfa fibers, or from a better match between nitrogen and energy supplies in the rumen. Alfalfa cultivars with improved fiber digestibility represent an opportunity to increase milk production, but no independent studies have tested these cultivars under the agroclimatic conditions of Canada. Moreover, decreasing metabolizable protein (MP) supply could increase N use efficiency while decreasing environmental impact, but it is often associated with a decrease in milk protein yield, possibly caused by a reduced supply of essential AA. This study evaluated the performance of dairy cows fed diets based on a regular or a reduced-lignin alfalfa cultivar and measured the effect of energy levels at low MP supply when digestible His (dHis), Lys (dLys), and Met (dMet) requirements were met. Eight Holstein cows were used in a double 4 × 4 Latin square design, each square representing an alfalfa cultivar. Within each square, 4 diets were tested: the control diet was formulated for an adequate supply of MP and energy (AMP_AE), whereas the 3 other diets were formulated to be deficient in MP (DMP; formulated to meet 90% of the MP requirement) with deficient (94% of requirement: DMP_DE), adequate (99% of requirement: DMP_AE), or excess energy supply (104% of requirement; DMP_EE). Alfalfa cultivars had no significant effect on all measured parameters. As compared with cows receiving AMP_AE, the dry matter intake of cows fed DMP_AE and DMP_EE was not significantly different but decreased for cows fed DMP_DE. The AMP_AE diet provided 103% of MP and 108% of NEL requirements whereas DMP_DE, DMP_AE, and DMP_EE diets provided 84, 87, and 87% of MP and 94, 101, and 107% of NEL requirements, respectively. In contrast to design, feeding DMP_EE resulted in a similar energy supply compared with AMP_AE, although MP supply has been effectively reduced. This resulted in a maintained milk and milk component yields and improved the efficiency of utilization of N, MP, and essential AA. The DMP diets decreased total N excretion, whereas DMP_AE and DMP_EE diets also decreased milk urea-N concentration. Reducing MP supply without negative effects on dairy cow performance is possible when energy, dHis, dLys, and dMet requirements are met. This could reduce N excretion and decrease the environmental impact of milk production.

Young adults (18- to 24-year-olds) constitute the age group with the highest proportion of cannabis users. In the context of legalization, it is important to promote lower-risk cannabis use. The Protective Behavioral Strategies for Marijuana Scale (PBSM-17) identifies strategies used by consumers. However, this scale is not available in French and is not adapted to the Canadian context. This article presents the process that led to the translation, cultural adaptation and evaluation of the preliminary psychometric properties of PBSM-17.The methodological study was carried out in six steps. The first four steps led to the translation towards French and adaptation of the scale. A validation among 12 young people contributed to establish the criterion equivalency (step 5). The evaluation of psychometric properties (step 6) was carried out among 211 bilingual university students (61 % women; mean age 22 years old).The French version presents satisfactory preliminary psychometric properties: internal consistency is acceptable (α = 0.88); criterion equivalency was established between the French and the original English version (t (210) = 1.04, p = 0.30; 95% CI [-0.20, 0.63]). The scores obtained on both versions by the same participant were found to be strongly correlated (r = 0.95, p0.001).The results support the use of the French version of PBSM-17. The proposed protective strategies can be used as a measurement tool and represent behaviors that can be targeted in a lower-risk cannabis use context.Les jeunes de 18 à 24 ans constituent la plus grande proportion de consommateurs de cannabis. Dans un contexte de légalisation de cette substance, il importe de promouvoir une consommation à moindre risque. L’échelleL’étude méthodologique s’est déroulée en six étapes. Les quatre premières étapes ont mené à la traduction et l’adaptation de l’échelle. La validation auprès de 12 jeunes a permis d’établir l’équivalence conceptuelle. L’évaluation des propriétés psychométriques a été réalisée auprès de 211 étudiants universitaires bilingues (61 % femme; âge moyen 22 ans).La version traduite et adaptée présente des propriétés psychométriques préliminaires satisfaisantes : la cohérence interne est acceptable (α = 0,88); l’équivalence de critères (validité de construit) est établie entre la version française et la version anglaise (Les résultats soutiennent l’utilisation de la version française du PBSM-17. Les stratégies de protection proposées peuvent être utilisées comme outil de mesure et représentent des comportements à adopter dans un contexte d’usage du cannabis à moindre risque.

Key Points Question Are hospital-at-home interventions consisting of, at minimum, home visits from nurses or physicians associated with better patient outcomes for adult patients with a chronic disease who present to an emergency department? Findings This systematic review of 9 randomized clinical trial studies, including 959 adult patients with a chronic disease, found that although patients receiving hospital-at-home care had an average length of treatment of 5.4 days longer than that of in-hospital patients and a similar mortality risk, they had a lower risk for readmission by 26% and a lower risk for long-term care admission relative to the in-hospital group. Patients who received hospital-at-home care also had lower depression and anxiety scores than patients receiving in-hospital care, but there was no difference in functional status. Meaning This systematic review provides further evidence that hospital-at-home interventions with at least 1 home visit from a nurse or physician may be a promising substitute to in-hospital care, especially for patients with chronic diseases who present to the emergency department., This meta-analysis investigates the association of hospital-at-home interventions vs in-hospital stay with patient outcomes in adults with chronic disease who present to an emergency department., Importance Hospitalizations are costly and may lead to adverse events; hospital-at-home interventions could be a substitute for in-hospital stays, particularly for patients with chronic diseases who use health services more than other patients. Despite showing promising results, heterogeneity in past systematic reviews remains high. Objective To systematically review and assess the association between patient outcomes and hospital-at-home interventions as a substitute for in-hospital stay for community-dwelling patients with a chronic disease who present to the emergency department and are offered at least 1 home visit from a nurse and/or physician. Data Sources Databases were searched from date of inception to March 4, 2019. The databases were Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, CINAHL, Health Technology Assessment, the Cochrane Library, OVID Allied and Complementary Medicine Database, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. Study Selection Randomized clinical trials in which the experimental group received hospital-at-home interventions and the control group received the usual in-hospital care. Patients were 18 years or older with a chronic disease who presented to the emergency department and received home visits from a nurse or physician. Data Extraction and Synthesis Risk of bias was assessed, and a meta-analysis was conducted for outcomes that were reported by at least 2 studies using comparable measures. Risk ratios (RRs) were reported for binary outcomes and mean differences for continuous outcomes. Narrative synthesis was performed for other outcomes. Main Outcomes and Measures Outcomes of interest were patient outcomes, which included mortality, long-term care admission, readmission, length of treatment, out-of-pocket costs, depression and anxiety, quality of life, patient satisfaction, caregiver stress, cognitive status, nutrition, morbidity due to hospitalization, functional status, and neurological deficits. Results Nine studies were included, providing data on 959 participants (median age, 71.0 years [interquartile range, 70.0-79.9 years]; 613 men [63.9%]; 346 women [36.1%]). Mortality did not differ between the hospital-at-home and the in-hospital care groups (RR, 0.84; 95% CI, 0.61-1.15; I2 = 0%). Risk of readmission was lower (RR, 0.74; 95% CI, 0.57-0.95; I2 = 31%) and length of treatment was longer in the hospital-at-home group than in the in-hospital group (mean difference, 5.45 days; 95% CI, 1.91-8.97 days; I2 = 87%). In addition, the hospital-at-home group had a lower risk of long-term care admission than the in-hospital care group (RR, 0.16; 95% CI, 0.03-0.74; I2 = 0%). Patients who received hospital-at-home interventions had lower depression and anxiety than those who remained in-hospital, but there was no difference in functional status. Other patient outcomes showed mixed results. Conclusions and Relevance The results of this systematic review and meta-analysis suggest that hospital-at-home interventions represent a viable substitute to an in-hospital stay for patients with chronic diseases who present to the emergency department and who have at least 1 visit from a nurse or physician. Although the heterogeneity of the findings remained high for some outcomes, particularly for length of treatment, the heterogeneity of this study was comparable to that of past reviews and further explored.

OBJECTIVE. PHACES syndrome includes posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities, and sternal defect with or without supraumbilical raphe. Usually, brain imaging is performed when facial hemangiomas are larger than 5 cm. Data on associated anomalies regardless of hemangioma size are sparse. The objective of this study was to determine, first, the prevalence of PHACES-like associated anomalies in a large sample of infants with all sizes of segmental facial or periorbital focal infantile hemangioma and, second, whether the cutaneous localization of the hemangioma correlates with the type of anomalies present. MATERIALS AND METHODS. The records of all patients of a vascular anomalies practice who had a diagnosis of segmental facial or periorbital focal infantile hemangioma and who had clinical photographs and brain MRI available were reviewed. The clinical photographs were reviewed to determine the localization by segment and lateralization. MRI was reviewed by two experienced pediatric radiologists. If present, cardiovascular anomalies, sternal defects, and eye anomalies were recorded. The criteria for definite and possible PHACES were used. RESULTS. The study included 122 children (90 girls, 32 boys; mean age, 16.6 months). Forty-five (36.9%) children had a facial infantile hemangioma larger than 5 cm. Twenty-two patients (18.0%) had PHACES or possible PHACES syndrome. Cerebrovascular structural anomalies were seen in 14 of 22 and brain anomalies in 6 of 22 patients with PHACES syndrome but in none and one of the patients in the group without PHACES (p < .001). Cardiovascular anomalies were seen in six patients and ocular anomalies in eight patients. All but one of them had PHACES syndrome. CONCLUSION. Clinical concern about associated extracutaneous anomalies is warranted for all children with facial segmental or periorbital focal infantile hemangiomas, including those with small hemangiomas. Further studies are needed to correlate cerebrovascular anomalies with the clinical evolution of hemangiomas and their effects on cerebral perfusion.

Background Transmission of pathogens by vector mosquitoes is intrinsically linked with mosquito’s reproductive strategy because anautogenous mosquitoes require vertebrate blood to develop a batch of eggs. Each cycle of egg maturation is tightly linked with the intake of a fresh blood meal for most species. Mosquitoes that acquire pathogens during the first blood feeding can transmit the pathogens to susceptible hosts during subsequent blood feeding and also vertically to the next generation via infected eggs. Large-scale gene-expression changes occur following each blood meal in various tissues, including ovaries. Here we analyzed mosquito ovary transcriptome following a blood meal at three different time points to investigate blood-meal induced changes in gene expression in mosquito ovaries. Results We collected ovaries from Aedes aegypti that received a sugar meal or a blood meal on days 3, 10 and 20 post blood meal for transcriptome analysis. Over 4000 genes responded differentially following ingestion of a blood meal on day 3, and 660 and 780 genes on days 10 and 20, respectively. Proteins encoded by differentially expressed genes (DEGs) on day 3 include odorant binding proteins (OBPs), defense-specific proteins, and cytochrome P450 detoxification enzymes. In addition, we identified 580 long non-coding RNAs that are differentially expressed at three time points. Gene ontology analysis indicated that genes involved in peptidase activity, oxidoreductase activity, extracellular space, and hydrolase activity, among others were enriched on day 3. Although most of the DEGs returned to the nonsignificant level compared to the sugar-fed mosquito ovaries following oviposition on days 10 and 20, there remained differences in the gene expression pattern in sugar-fed and blood-fed mosquitoes. Conclusions Enrichment of OBPs following blood meal ingestion suggests that these genes may have other functions besides being part of the olfactory system. The enrichment of immune-specific genes and cytochrome P450 genes indicates that ovaries become well prepared to protect their germ line from any pathogens that may accompany the blood meal or from environmental contamination during oviposition, and to deal with the detrimental effects of toxic metabolites.

The use of radioactive isotopes to measure de novo lipogenesis in pigs has been well established. Different from radioactive isotopes, stable isotopes present little or no risk to human and animal subjects. Therefore, the objective of this study was to adapt the method of bolus injection of radioactive glucose (14C) to use 13C-labeled glucose to estimate de novo lipogenesis in finishing pigs. Five vein-catheterized gilts received 3.0 kg/d of a commercial diet for 2 wk. On the last day, the pigs received a bolus injection of [U-13C]glucose (12 mg/kg body weight). A serial of blood samples was taken for 4 h to determine the glucose rate of disappearance (Rd) from plasma glucose isotopic enrichment (IE). The 13C IE of lipids was determined from adipose tissue biopsies collected at 1, 2, and 3 h after the bolus injection and from adipose tissue collected after pig euthanasia 4 h after the bolus. Lipogenesis was estimated from the incorporation of 13C from glucose into adipose tissue lipids. Glucose Rd, estimated using a double-exponential function, averaged 5.4 ± 1.4 mmol/min. The IE of lipids increased linearly during the 4 h following the bolus injection (P < 0.05). The rate of incorporation of glucose into lipids, estimating lipogenesis, averaged 9.0 µg glucose/(min × g of lipids) 4 h after the bolus injection. In conclusion, the in vivo method using a bolus injection of [U-13C]glucose allows a successful estimation of de novo lipogenesis in finishing pigs.

Background We compared early outcomes, at a single academic institution, of implementing full coronary revascularization in coronary artery bypass grafting using multiarterial Y‐composite grafts with multiple sequential anastomoses. Methods and Results Clinical records of 425 consecutive patients who underwent coronary artery bypass grafting using Y‐grafting with left internal mammary artery and radial artery (Y‐RA group) or right internal mammary artery (Y‐RIMA group) from 2015 to 2019, were reviewed. These were compared with the institutional experience of isolated coronary artery bypass grafting cases (in situ on pump/off pump) for the same period of time. When comparing the 4 groups, the Y‐RIMA/RA groups revealed a higher number of distal anastomosis than the in situ on‐ or off‐pump groups. When the number of distal arterial anastomosis was analyzed, there was a superiority of using the Y‐configuration compared with the in situ approach. Moreover, there were no significant differences among groups for mortality and/or major adverse cardiac and cerebrovascular events in hospital or at 30‐day follow‐up. A subanalysis comparing the Y‐RIMA group with the Y‐RA group showed that complementary grafts to the Y‐construct were required to accomplish full revascularization more frequently in the Y‐RIMA group. Full‐arterial revascularization was achieved in 92.2% of the Y‐RA group and 72.0% of the Y‐RIMA group ( P P Conclusions The 2 types of arterial Y‐composite grafting were able to be introduced in the routine practice of our institution showing comparable results to the established institutional practice. This procedure allowed for more arterial distal anastomosis to be performed safely without compromising outcomes.

Background Infections with the tapeworm Taenia solium (taeniosis and cysticercosis) are Neglected Tropical Diseases (NTD) highly endemic in Madagascar. These infections are however underdiagnosed, underreported and their burden at the community level remains unknown especially in rural remote settings. This study aims at assessing the prevalence of T. solium infections and associated risk factors in twelve remote villages surrounding Ranomafana National Park (RNP), Ifanadiana District, Madagascar. Methodology A community based cross-sectional survey was conducted in June 2016. Stool and serum samples were collected from participants. Tapeworm carriers were identified by stool examination. Taenia species and T. solium genotypes were characterised by PCR and sequencing of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Detection of specific anti-cysticercal antibodies (IgG) or circulating cysticercal antigens was performed by ELISA or EITB/Western blot assays. Principal findings Of the 459 participants with paired stool and blood samples included ten participants from seven distinct villages harbored Taenia spp. eggs in their stools samples DNA sequencing of the cox1 gene revealed a majority of T. solium Asian genotype (9/10) carriage. The overall seroprevalences of anti-cysticercal IgGs detected by ELISA and EITB were quite similar (27.5% and 29.8% respectively). A prevalence rate of 12.4% of circulating cysticercal antigens was observed reflecting cysticercosis with viable cysts. Open defecation (Odds Ratio, OR = 1.5, 95% CI: 1.0–2.3) and promiscuity with households of more than 4 people (OR = 1.9, 95% CI: 1.1–3.1) seem to be the main risk factors associated with anticysticercal antibodies detection. Being over 15 years of age would be a risk factor associated with an active cysticercosis (OR = 1.6, 95% CI: 1.0–2.7). Females (OR = 0.5, 95% CI: 0.3–0.9) and use of river as house water source (OR = 0.3, 95% CI: 0.1–1.5) were less likely to have cysticercosis with viable cysts. Conclusions/Significance This study indicates a high exposure of the investigated population to T. solium infections with a high prevalence of cysticercosis with viable cysts. These data can be useful to strengthen public health interventions in these remote settings.

Why does prenatal exposure to wars, natural disasters, urbanicity, or winter increase the risk for schizophrenia? Research from the last two decades has provided rich insight about the underlying chains of causation at play during environmental upheaval, from conception to early infancy. In this review, we appraise the evidence linking schizophrenia spectrum disorder to prenatal maternal stress, obstetric complications, early infections, and maternal nutrition and other lifestyle factors. We discuss putative mechanisms, including the maternal stress system, perinatal hypoxia, and maternal–offspring immune activation. We propose that gene–environment interactions, timing during development, and sex differentiate the neuropsychiatric outcomes. Future research should pursue the translation of animal studies to humans and the longitudinal associations between early exposures, intermediate phenotypes, and psychiatric disorders. Finally, to paint a comprehensive model of risk and to harness targets for prevention, we argue that risk factors should be situated within the individual's personal ecosystem.

Background and Purpose: The aim of this study was to evaluate and independently validate SAA (serum amyloid A)—a recently discovered blood biomarker—to predict poststroke infections. Methods: The derivation cohort (A) was composed of 283 acute ischemic stroke patients and the independent validation cohort (B), of 367 patients. The primary outcome measure was any stroke-associated infection, defined by the criteria of the US Centers for Disease Control and Prevention, occurring during hospitalization. To determine the association of SAA levels on admission with the development of infections, logistic regression models were calculated. The discriminatory ability of SAA was assessed, by calculating the area under the receiver operating characteristic curve. Results: After adjusting for all predictors that were significantly associated with any infection in the univariate analysis, SAA remained an independent predictor in study A (adjusted odds ratio, 1.44 [95% CI, 1.16–1.79]; P =0.001) and in study B (adjusted odds ratio, 1.52 [1.05–2.22]; P =0.028). Adding SAA to the best regression model without the biomarker, the discriminatory accuracy improved from 0.76 (0.69–0.83) to 0.79 (0.72–0.86; P P Conclusions: Among patients with ischemic stroke, blood SAA measured on admission is a novel independent predictor of infection after stroke. SAA improved the discrimination between patients who developed an infection compared with those who did not in both derivation and validation cohorts. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00390962.

We describe two sporadic and two familial cases with loss-of-function variants in PRPS1, which is located on the X chromosome and encodes phosphoribosyl pyrophosphate synthetase 1 (PRS-1). We illustrate the clinical variability associated with decreased PRS-1 activity, ranging from mild isolated hearing loss to severe encephalopathy. One of the variants we identified has already been reported with a phenotype similar to our patient's, whereas the other three were unknown. The clinical and biochemical information we provide will hopefully contribute to gain insight into the correlation between genotype and phenotype of this rare condition, both in females and in males. Moreover, our observation of a new family in which hemizygous males display hearing loss without any neurological or ophthalmological symptoms prompts us to suggest analysing PRPS1 in cases of isolated hearing loss. Eventually, PRPS1 variants should be considered as a differential diagnosis of mitochondrial disorders.

Prolactin production is controlled by a complex and temporally dynamic network of factors. Despite this tightly coordinated system, pathological hyperprolactinemia is a common endocrine disorder that is often not understood, thereby highlighting the need to expand our molecular understanding of lactotroph cell regulation. MicroRNA-7 (miR-7) is the most highly expressed miRNA family in the pituitary gland and the loss of the miR-7 family member, miR-7a2, is sufficient to reduce prolactin gene expression in mice. Here, we used conditional loss-of-function and gain-of-function mouse models to characterize the function of miR-7a2 in lactotroph cells. We found that pituitary miR-7a2 expression undergoes developmental and sex hormone–dependent regulation. Unexpectedly, the loss of mir-7a2 induces a premature increase in prolactin expression and lactotroph abundance during embryonic development, followed by a gradual loss of prolactin into adulthood. On the other hand, lactotroph development is delayed in mice overexpressing miR-7a2. This regulation of lactotroph function by miR-7a2 involves complementary mechanisms in multiple cell populations. In mouse pituitary and rat prolactinoma cells, miR-7a2 represses its target Raf1, which promotes prolactin gene expression. These findings shed light on the complex regulation of prolactin production and may have implications for the physiological and pathological mechanisms underlying hyperprolactinemia.

Background The influence of sex and gender on the risk of dementia, its clinical presentation and progression is increasingly being recognized. However, current dementia strategies have not explicitly considered sex and gender differences in the management of dementia to ensure equitable care. The objective of this study was to examine the moderating effect of sex on the quality of care following the implementation of the Quebec Alzheimer Plan (QAP). Methods We conducted a secondary analysis of the evaluation of the QAP consisting of a retrospective chart review of 945 independent, randomly-selected patient charts of males and females 75+ years old with dementia and a visit to one of 13 participating Family Medicine Groups before (October 2011–July 2013) and after (October 2014 – July 2015). The quality of dementia care score, based on Canadian and international recommendations and consensus guidelines, consisted of documented assessments in 10 domains. We used a mixed linear regression model to measure the interaction between sex and the implementation of the QAP on the quality of dementia care score, adjusting for age and number of medications. Results We found that improvements in the quality of dementia care following the QAP were larger for men than women (mean difference = 4.97; 95%CI: 0.08, 9.85). We found that men had a larger improvement in four indicators (driving assessments, dementia medication management, Alzheimer Society referrals, and functional status evaluation), while women had a smaller improvement in three (home care needs, behavioural and psychological symptoms of dementia, and weight). Men were prescribed fewer anticholinergics post-QAP, while women were prescribed more. Cognitive testing improved in men but decreased for women following the QAP; the opposite was observed for caregiver needs. Conclusion While the overall quality of care improved after the implementation of the QAP, this study reveals differences in dementia management between men and women. While we identified areas of inequalities in the care received, it is unclear whether this represents inequities in access to care and health outcomes. Future research should focus on better understanding sex and gender-specific needs in dementia to bridge this gap and better inform dementia strategies.

Dating violence (DV) among youth is widespread and is now established as a significant public health problem. Yet, few studies have assessed DV experiences among youth with same-gender or multi-gender dating partners, and most failed to consider bidirectional DV. We analyzed self-reported dyadic concordance types (DCTs) among 295 youths (52% girls) who dated same-gender and multi-gender partners in the last 12 months using an adapted version of the Conflict in Adolescent Dating Relationships Inventory. Youths were classified in one of three DCTs: self-only (unidirectional perpetration of DV by the participant), partner-only (unidirectional victimization perpetrated by their partner) or both (bidirectional DV, where partners are both perpetrators and victims of DV). Overall prevalence rates of DV among sexual minority youths (SMYs) range from 11.5% for threats, to 51.2% for psychological violence, with physical and sexual violence reported by about one-fourth of participants. The both DCT was the most common pattern for psychological (59.6%) and physical (50.6%) DV across gender, while most threatening behaviors were reported as perpetrated by the partner only (47.1%). Girls were more likely to report sexual DV as partner-only perpetrated (63.6%), whereas boys reported higher rates of both (44.2%) and self-only (34.9%) perpetrated sexual violence. Because healthy intimate relationships can play a supportive and positive role in transitioning toward adulthood, it is crucial that DV prevention becomes more inclusive of sexual and gender diversity.

Supravalvular pulmonary stenosis (SVPS) is considered a rare form of pulmonary stenosis (PS) and represents both a diagnostic and therapeutic challenge. There currently exist no reliable echocardiographic criteria to accurately predict the supravalvular form. The aims of the study were to describe the response to treatment of the different PS presentations and to outline the diagnostic capacity of echocardiogram to differentiate the SVPS from valvular PS (VPS). This retrospective study included 106 patients who underwent percutaneous angioplasty between 2006 and 2017. Interventional outcomes of patients with SVPS were compared to those of patients with VPS. Diagnosis of VPS vs. SVPS by echocardiogram was compared to diagnosis obtained by angiogram. Echocardiogram yielded a sensitivity of 56%, a specificity of 82.5%, a positive predictive value of 50%, and a negative predictive value of 85.7%. Patients with SVPS had a significantly smaller pulmonary artery to pulmonary valve (PA:PV) ratio. At 6–12 months of follow-up, the VPS group had a mean right ventricular to pulmonary artery (RV-PA) gradient of 21.68 ± 19.85 mmHg compared to 45.27 ± 24.58 mmHg in the SVPS group. Patients with SVPS had a higher rate of reintervention than patients with VPS (32% vs. 6.2%, p

This study aimed to examine the link between friendship instability during emerging adulthood and depressive symptoms. The moderating role of gender and the pursuit (or not) of postsecondary educat...

Purpose The objective of this exploratory study was to evaluate the effects of a brief intervention intended to optimize the sleep environment in older people living in the community and to examine the way these effects change over time. Methods The sample was made up of 44 participants (19 men and 25 women) aged 65–85 years, with a mean age of 71.4. The intervention consisted in a group training session that covered the reasons for and ways to (“why” and “how”) optimize a sleep environment. It comprises six themes: air quality and odors, luminosity, noises and sounds, comfort of the mattress, comfort of the pillow, and temperature. Participants completed a set of questionnaires before the intervention, and one month and four months later. Results Four months after the intervention, the replies to the questionnaires showed that the participants experienced reduced severity of insomnia, sleep latency and anxiety. The subjective quality of the participants’ sleep along with their sleep efficacy also increased significantly during the same period. Conclusion A brief intervention intended to optimize the sleep environment appears promising as an addition or alternative to the two other sleep improvement options generally offered to older people: medication and cognitive behavioral therapy.

The psychoactive component in cannabis, delta‐9‐tetrahydrocannabinol, can restrict fetal growth and development. Delta‐9‐tetrahydrocannabinol has been shown to negatively impact cellular proliferation and target organelles like the mitochondria resulting in reduced cellular respiration. In the placenta, mitochondrial dysfunction leading to oxidative stress prevents proper placental development and function. A key element of placental development is the proliferation and fusion of cytotrophoblasts to form the syncytium that comprises the materno‐fetal interface. The impact of delta‐9‐tetrahydrocannabinol on this process is not well understood. To elucidate the nature of the mitochondrial dysfunction and its consequences on trophoblast fusion, we treated undifferentiated and differentiated BeWo human trophoblast cells, with 20 µM delta‐9‐tetrahydrocannabinol for 48 hr. At this concentration, delta‐9‐tetrahydrocannabinol on BeWo cells reduced the expression of markers involved in syncytialization and mitochondrial dynamics, but had no effect on cell viability. Delta‐9‐tetrahydrocannabinol significantly attenuated the process of syncytialization and induced oxidative stress responses in BeWo cells. Importantly, delta‐9‐tetrahydrocannabinol also caused a reduction in the secretion of human chorionic gonadotropin and the production of human placental lactogen and insulin growth factor 2, three hormones known to be important in facilitating fetal growth. Furthermore, we also demonstrate that delta‐9‐tetrahydrocannabinol attenuated mitochondrial respiration, depleted adenosine triphosphate, and reduced mitochondrial membrane potential. These changes were also associated with an increase in cellular reactive oxygen species, and the expression of stress responsive chaperones, HSP60 and HSP70. These findings have important implications for understanding the role of delta‐9‐tetrahydrocannabinol‐induced mitochondrial injury and the role this might play in compromising human pregnancies., THC disrupted mitochondrial function, increased markers of mitochondrial fission and cellular stress in BeWo cells. This was coincident with reduced BeWo cell fusion and secretion of important fetal growth signals, hPL and IGF2. These changes were mediated, in part, via the CB1 receptor in syncytialized BeWo cells.

Here, we used a mouse model with defective autophagy to further decipher the role of Beclin1 in the infection and disease of Zika virus (ZIKV)-R103451. Hemizygous (Becn1+/&minus, ) and wild-type (Becn1+/+) pregnant mice were transiently immunocompromised using the anti-interferon alpha/beta receptor subunit 1 monoclonal antibody MAR1-5A3. Despite a low mortality rate among the infected dams, 25% of Becn1+/&minus, offspring were smaller in size and had smaller, underdeveloped brains. This phenotype became apparent after 2-to 3-weeks post-birth. Furthermore, the smaller-sized pups showed a decrease in the mRNA expression levels of insulin-like growth factor (IGF)-1 and the expression levels of several microcephaly associated genes, when compared to their typical-sized siblings. Neuronal loss was also noticeable in brain tissues that were removed postmortem. Further analysis with murine mixed glia, derived from ZIKV-infected Becn1+/&minus, and Becn1+/+ pups, showed greater infectivity in glia derived from the Becn1+/&minus, genotype, along with a significant increase in pro-inflammatory molecules. In the present study, we identified a link by which defective autophagy is causally related to increased inflammatory molecules, reduced growth factor, decreased expression of microcephaly-associated genes, and increased neuronal loss. Specifically, we showed that a reduced expression of Beclin1 aggravated the consequences of ZIKV infection on brain development and qualifies Becn1 as a susceptibility gene of ZIKV congenital syndrome.