An Experimental Phototherapy Device for Studying the Effects of Blue Light on Patients with Raynaud's Phenomenon.

Raynaud's phenomenon (RP) is a condition that causes decreased blood flow to areas perfused by small blood vessels (e.g., fingers, toes). In severe cases, ulceration, gangrene, and loss of fingers may occur. Most treatments focus on inducing vasorelaxation in affected areas by the way of pharmaceuticals. Recently, animal studies have shown that vasorelaxation can be induced by non-coherent blue light (wavelength ~ 430-460 nm) through the actions of melanopsin, a photoreceptive opsin protein encoded by the OPN4 gene. To study this effect in humans, a reliable phototherapy device (PTD) is needed. We outline the construction of a PTD to be used in studying blue light effects on Raynaud's patients. Our design addresses user safety, calibration, electromagnetic compatibility/interference (EMC/EMI), and techniques for measuring physiological responses (temperature sensors, laser Doppler flow sensors, infrared thermal imaging of the hands). We tested our device to ensure (1) safe operating conditions, (2) predictable, user-controlled irradiance output levels, (3) an ability for measuring physiological responses, and (4) features necessary to enable a double-blinded crossover study for a clinical trial. We also include in the Methods an approved research protocol utilizing our device that may serve as a starting point for clinical study. We introduced a reliable PTD for studying the effects of blue light therapy for patients suffering from Raynaud's phenomenon and showed that our device is safe and reliable and includes the required measurement vectors for tracking treatment effects throughout the duration of a clinical study.

Measles: Contemporary considerations for the emergency physician.

Measles, or rubeola, is a highly contagious acute febrile viral illness. Despite the availability of an effective vaccine since 1963, measles outbreaks continue worldwide. This article seeks to provide emergency physicians with the contemporary knowledge required to rapidly diagnose potential measles cases and bolster public health measures to reduce ongoing transmission.

Recall of Awareness During Paralysis Among ED Patients Undergoing Tracheal Intubation.

BACKGROUND: Critically ill patients sometimes remember periods of neuromuscular blockade. RESEARCH QUESTION: What is the prevalence of recalled awareness during paralysis in patients who underwent emergency tracheal intubation and mechanical ventilation, and what clinical variables are associated with this outcome? STUDY DESIGN AND METHODS: This study analyzed data from a prospectively collected continuous quality improvement database of emergency tracheal intubation in an urban, county hospital. Patients who received a neuromuscular blocking agent to facilitate emergency tracheal intubation in the ED were included. The database contained details of intubation management, including medications received and patient mental status prior to intubation. Patient recall of awareness of paralysis was assessed by trained staff during an in-person interview following extubation using a modified Brice questionnaire. For this analysis, three expert reviewers used these data to adjudicate whether patients may have had awareness of paralysis, the primary outcome. A logistic regression model was constructed to determine whether clinical variables were associated with the primary outcome. RESULTS: A total of 886 patients were analyzed. There were 66 patients (7.4%; 95% CI, 5.8-9.4) determined to possibly (61 patients) or definitely (5 patients) have experienced and recalled awareness of paralysis. A logistic regression model revealed that a decreased level of consciousness prior to intubation was associated with lower odds of awareness (adjusted OR, 0.39; 95% CI, 0.22-0.69), whereas the class of neuromuscular blocking agent used, sedative used, preintubation shock index, and postintubation sedation were not significantly associated with recall of this outcome. INTERPRETATION: Among patients intubated emergently using a neuromuscular blocking agent, 7.4% of patients recalled awareness without being able to move, which was more likely when patients had a normal level of consciousness prior to intubation.

Yoga and nonsuicidal self-injury: Mediational effects of self-compassion and body appreciation.

Non-suicidal self-injury (NSSI) is a prevalent maladaptive body-focused behavior among youth and young adults. Yoga is associated with improved mindfulness, body image, and self-compassion; all of which are associated with decreased NSSI. This study evaluated the relationship between yoga and NSSI frequency, and if the relationship would be mediated by mindfulness, self-compassion, and/or body appreciation. Participants were recruited from a random sample of university students via email and included those with some yoga experience (N = 384; Mage = 19.98, SD = 2.20). Participants completed an anonymous online survey assessing their levels of yoga participation, NSSI, mindfulness, self-compassion, and body appreciation. Bias corrected serial mediation regression models indicated the relationship between yoga participation and NSSI frequency was significantly mediated by self-compassion followed by body appreciation. Body appreciation was also a significant single mediator of yoga's relationship with NSSI. Mindfulness was not a significant mediator in any of the analyzes. Yoga practice is associated with reduced NSSI behaviors through its positive relationships with body appreciation and self-compassion. Body appreciation appears to be an important mechanism underlying the link between yoga participation and NSSI behavior suggesting that interventions promoting positive body image, such as yoga, could be innovative strategies for clinicians to consider.

Flexibility in Faculty Work-Life Policies at Medical Schools in the Big Ten Conference: A Ten-Year Follow-up Study.

Background: Flexible work-life policies for medical school faculty are necessary to support career progress, advancement, retention, and job satisfaction. Objective: Our objective was to perform a 10-year follow-up descriptive assessment of the availability of flexible work-life policies for faculty in medical schools in the Big Ten Conference. Design: In this descriptive study, a modified objective scoring system was used to evaluate the flexibility of faculty work-life policies at 13 medical schools in the Big Ten Conference. Policy information was obtained from institutional websites and verified with the human resources offices. Scores from the 2011 study and 2020 were compared. Results: Michigan State and Ohio State Universities offered the most flexible policies (score 17.75/22) with the Universities of Maryland and Minnesota following (score 16/22). The largest delta scores, indicating more flexible policies in the past decade, were at University of Minnesota (5.25) and University of Michigan (5). Policies for parental leave and part-time faculty varied widely. Most schools earned an additional point in the newly added category of "flexible scheduling and return-to-work policies." Nearly every institution reported dedicated lactation spaces and improved childcare options. Limitations : Limitations included missing policy data and interpretation bias in reviewing the policy websites, unavailable baseline data for schools that joined the Big Ten after the 2011 study, and unavailable baseline data for the additional category of return-to-work policies. Conclusions: While progress has been made, every institution should challenge themselves to review flexibility in work-life policies for faculty. It is important to advance a healthy competition with the goal to achieve more forward-thinking policies that improve retention, recruitment, and advancement of faculty. Big Ten institutions can continue to advance their policies by providing greater ease of access to options, further expansion of parental leave and childcare support, and offering more flexible policies for part-time faculty.

An unusual case of epistaxis in a four month old.

Epistaxis is a routine complaint in Emergency Medicine and presents most commonly in adults and children and its incidence increases with age. It is rare in infants and neonates. We discuss a case of epistaxis in a four-month-old male who presented to a critical access hospital. What initially appeared to be routine brisk epistaxis was later discovered to be a large, complex, epiglottic hemangioma. The patient was stabilized using topical tranexamic acid, nasal packing with ketamine sedation, and sent to a tertiary care center for definitive management. He required advanced airway management in the OR for definitive airway management for airway-obstructing hemangioma excision.

Proteomic and functional mapping of cardiac NaV1.5 channel phosphorylation sites.

Phosphorylation of the voltage-gated Na+ (NaV) channel NaV1.5 regulates cardiac excitability, yet the phosphorylation sites regulating its function and the underlying mechanisms remain largely unknown. Using a systematic, quantitative phosphoproteomic approach, we analyzed NaV1.5 channel complexes purified from nonfailing and failing mouse left ventricles, and we identified 42 phosphorylation sites on NaV1.5. Most sites are clustered, and three of these clusters are highly phosphorylated. Analyses of phosphosilent and phosphomimetic NaV1.5 mutants revealed the roles of three phosphosites in regulating NaV1.5 channel expression and gating. The phosphorylated serines S664 and S667 regulate the voltage dependence of channel activation in a cumulative manner, whereas the nearby S671, the phosphorylation of which is increased in failing hearts, regulates cell surface NaV1.5 expression and peak Na+ current. No additional roles could be assigned to the other clusters of phosphosites. Taken together, our results demonstrate that ventricular NaV1.5 is highly phosphorylated and that the phosphorylation-dependent regulation of NaV1.5 channels is highly complex, site specific, and dynamic.

Investigation of factors associated with spontaneous preterm birth in pregnant women living with HIV.

OBJECTIVE: To investigate factors contributing to preterm birth (PTB), including cART use and clinical and social determinants of health, in women living with HIV (WLWH) from British Columbia, Canada. DESIGN: Retrospective observational cohort. METHODS: We investigated the effect of cART use and other clinical and demographic factors on spontaneous PTB (sPTB) rates (<37 weeks gestational age) among 631 singleton pregnancies between 1997 and 2018. Exposure to cART was modelled in comparison to no exposure, exposure in the first trimester, and between regimens. Differences in sPTB risk were estimated using time-dependent Cox's proportional hazards models. RESULTS: Overall, the sPTB rate was 16%. Cumulative cART use was associated with lower risk of PTB (Wald test P = 0.02; hazard ratio = 0.98, 95% CI = 0.96-0.99) and specific cART regimens were not associated with increased risk of sPTB. Exposure in the first trimester was not associated with sPTB and for each week of cART exposure, the risk of sPTB decreased by 2%. In a multivariable model, HIV viral load and substance use remained associated with risk of sPTB, but not cART exposure. CONCLUSION: The sPTB rate among pregnant WLWH was more than three times higher than in the general population. However, sPTB was not related specifically to use of cART; in fact, cART appeared to reduce the risk of sPTB. Uncontrolled HIV replication and substance use were associated with increased risk of sPTB among pregnant WLWH. This emphasizes the important role of prenatal care, access to cART, and smoking cessation and harm reduction to reduce the risk of sPTB in WLWH.

Toxicity of Bupropion Overdose Compared With Selective Serotonin Reuptake Inhibitors.

OBJECTIVES: Adolescent depression and attempted and completed suicide are increasing in the United States. Because suicide is often impulsive, the means of self-harm are frequently items of convenience like medication. Authors of a recent study compared tricyclic antidepressant overdose to bupropion overdose. Fluoxetine and escitalopram are the only agents with Food and Drug Administration approval for pediatric depression, but off-label bupropion prescriptions are common. We sought to compare the effects of selective serotonin reuptake inhibitors (SSRIs) and bupropion in overdose. METHODS: This was an analysis of the National Poison Data System from June 2013 through December 2017 for adolescent (ages 10-19) exposures to SSRIs or bupropion coded as "suspected suicide." Demographics, clinical effects, therapies, and medical outcome were analyzed. RESULTS: There were 30 026 cases during the study period. Sertraline and fluoxetine accounted for nearly 60%, whereas bupropion was reported in 11.7%. Bupropion exposure was significantly associated with death (0.23% vs 0%; P < .001) or serious outcome (58.1% vs 19%; P < .001) as well as the 10 most common clinical effects, including seizures (27.0% vs 8.5%; P < .001) and hallucinations (28.6% vs 4.3%; P < .001). Bupropion exposure was significantly associated with the need for cardiopulmonary resuscitation (0.51% vs 0.01%; P < .001), intubation (4.9% vs 0.3%; P < .001), vasopressors (1.1% vs 0.2%; P < .001), and benzodiazepines (34.2% vs 5.5%; P < .001). There was a significant increase in all exposures and in proportion of serious outcomes over time. CONCLUSIONS: Adolescents who attempt self-harm are at higher risk for serious morbidity and poor outcomes with bupropion than with SSRIs. These risks, and the patient's propensity for self-harm, should be evaluated when therapy with bupropion is considered.

Tumor-intrinsic response to IFNγ shapes the tumor microenvironment and anti-PD-1 response in NSCLC.

Targeting PD-1/PD-L1 is only effective in ∼20% of lung cancer patients, but determinants of this response are poorly defined. We previously observed differential responses of two murine K-Ras-mutant lung cancer cell lines to anti-PD-1 therapy: CMT167 tumors were eliminated, whereas Lewis Lung Carcinoma (LLC) tumors were resistant. The goal of this study was to define mechanism(s) mediating this difference. RNA sequencing analysis of cancer cells recovered from lung tumors revealed that CMT167 cells induced an IFNγ signature that was blunted in LLC cells. Silencing Ifngr1 in CMT167 resulted in tumors resistant to IFNγ and anti-PD-1 therapy. Conversely, LLC cells had high basal expression of SOCS1, an inhibitor of IFNγ. Silencing Socs1 increased response to IFNγ in vitro and sensitized tumors to anti-PD-1. This was associated with a reshaped tumor microenvironment, characterized by enhanced T cell infiltration and enrichment of PD-L1hi myeloid cells. These studies demonstrate that targeted enhancement of tumor-intrinsic IFNγ signaling can induce a cascade of changes associated with increased therapeutic vulnerability.

Understanding Men's Perceptions of Human Papillomavirus and Cervical Cancer Screening in Kampala, Uganda.

PURPOSE: This preliminary study explores Ugandan men's knowledge and attitudes about human papillomavirus (HPV), cervical cancer, and screening. METHODS: A local physician led an education session about cervical cancer for 62 men in Kisenyi, Kampala in Uganda. Trained nurse midwives administered surveys to assess knowledge and attitudes before and after the education session. RESULTS: From the pre-education survey, only 24.6% of men had heard of HPV previously, and 59% of men had heard of cervical cancer. Posteducation, 54.5% of men believed only women could be infected with HPV and 32.7% of men believed antibiotics could cure HPV. Despite their limited knowledge, 98.2% of men stated they would support their partners to receive screening for cervical cancer, and 100% of men surveyed stated they would encourage their daughter to get the HPV vaccine if available. CONCLUSIONS: Knowledge of HPV and cervical cancer among Ugandan men is low. Even after targeted education, confusion remained about disease transmission and treatment. Ongoing education programs geared toward men and interventions to encourage spousal communication about reproductive health and shared decision making may improve awareness of cervical cancer prevention strategies.

Human Immunodeficiency Virus Viral Load Rebound Near Delivery in Previously Suppressed, Combination Antiretroviral Therapy-Treated Pregnant Women.

OBJECTIVE: To assess the stability of human immunodeficiency virus (HIV) viral load suppression within 1 month before birth in pregnant women receiving antenatal combination antiretroviral therapy (CART). METHODS: This is a retrospective cohort study of a Canadian provincial perinatal HIV database from 1997 to 2015. Inclusion criteria were live birth and CART received for at least 4 weeks. Viral load rebound, defined as viral load greater than 50 copies/mL (or greater than 400 copies/mL for 1997-1998) and measured within 1 month before delivery, was identified in women who had at least one previous undetectable viral load during pregnancy. Logistic regressions were conducted to identify the risk factors for viral load rebound. RESULTS: Among the 470 women in the database, 318 met inclusion criteria. Viral load rebound was experienced by 19 women (6.0%, 95% CI 3.7-9.3%) with a mean log10 viral load near delivery of 2.71 copies/mL (=513 copies/mL). Six (32%) had a viral load above 1,000 copies/mL. The rebound was detected within 1 day before delivery in 50% of the women. Aboriginal ethnicity, cocaine use, and hepatitis C virus polymerase chain reaction positivity were significantly associated with viral load rebound. There were no HIV vertical transmissions. CONCLUSION: Even women attending for HIV care and achieving viral suppression in pregnancy can experience viral load rebound predelivery.

High Diversity and Variability in the Vaginal Microbiome in Women following Preterm Premature Rupture of Membranes (PPROM): A Prospective Cohort Study.

OBJECTIVE: To characterize the vaginal microbiota of women following preterm premature rupture of membranes (PPROM), and determine if microbiome composition predicts latency duration and perinatal outcomes. DESIGN: A prospective cohort study. SETTING: Canada. POPULATION: Women with PPROM between 24+0 and 33+6 weeks gestational age (GA). METHODS: Microbiome profiles, based on pyrosequencing of the cpn60 universal target, were generated from vaginal samples at time of presentation with PPROM, weekly thereafter, and at delivery. MAIN OUTCOME MEASURES: Vaginal microbiome composition, latency duration, gestational age at delivery, perinatal outcomes. RESULTS: Microbiome profiles were generated from 70 samples from 36 women. Mean GA at PPROM was 28.8 wk (mean latency 2.7 wk). Microbiome profiles were highly diverse but sequences representing Megasphaera type 1 and Prevotella spp. were detected in all vaginal samples. Only 13/70 samples were dominated by Lactobacillus spp. Microbiome profiles at the time of membrane rupture did not cluster by gestational age at PPROM, latency duration, presence of chorioamnionitis or by infant outcomes. Mycoplasma and/or Ureaplasma were detected by PCR in 81% (29/36) of women, and these women had significantly lower GA at delivery and correspondingly lower birth weight infants than Mycoplasma and/or Ureaplasma negative women. CONCLUSION: Women with PPROM had mixed, abnormal vaginal microbiota but the microbiome profile at PPROM did not correlate with latency duration. Prevotella spp. and Megasphaera type I were ubiquitous. The presence of Mollicutes in the vaginal microbiome was associated with lower GA at delivery. The microbiome was remarkably unstable during the latency period.

A Study of the Vaginal Microbiome in Healthy Canadian Women Utilizing cpn60-Based Molecular Profiling Reveals Distinct Gardnerella Subgroup Community State Types.

The vaginal microbiota is important in women's reproductive and overall health. However, the relationships between the structure, function and dynamics of this complex microbial community and health outcomes remain elusive. The objective of this study was to determine the phylogenetic range and abundance of prokaryotes in the vaginal microbiota of healthy, non-pregnant, ethnically diverse, reproductive-aged Canadian women. Socio-demographic, behavioural and clinical data were collected and vaginal swabs were analyzed from 310 women. Detailed profiles of their vaginal microbiomes were generated by pyrosequencing of the chaperonin-60 universal target. Six community state types (CST) were delineated by hierarchical clustering, including three Lactobacillus-dominated CST (L. crispatus, L. iners, L. jensenii), two Gardnerella-dominated (subgroups A and C) and an "intermediate" CST which included a small number of women with microbiomes dominated by seven other species or with no dominant species but minority populations of Streptococcus, Staphylococcus, Peptoniphilus, E. coli and various Proteobacteria in co-dominant communities. The striking correspondence between Nugent score and deep sequencing CST continues to reinforce the basic premise provided by the simpler Gram stain method, while additional analyses reveal detailed cpn60-based phylogeny and estimated abundance in microbial communities from vaginal samples. Ethnicity was the only demographic or clinical characteristic predicting CST, with differences in Asian and White women (p = 0.05). In conclusion, this study confirms previous work describing four cpn60-based subgroups of Gardnerella, revealing previously undescribed CST. The data describe the range of bacterial communities seen in Canadian women presenting with no specific vaginal health concerns, and provides an important baseline for future investigations of clinically important cohorts.

Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women.

INTRODUCTION: Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period. METHODS: This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30-40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR. RESULTS: Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001). CONCLUSIONS: In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is another step toward optimizing the safety and efficacy of cART regimens during pregnancy.

Obstetrical and neonatal outcomes among women infected with hepatitis C and their infants.

OBJECTIVES: (1) To describe obstetrical and neonatal outcomes among a cohort of hepatitis C virus (HCV) infected women, comparing HCV RNA positive to HCV RNA negative women; (2) to characterize virologic and hepatic parameters associated with HCV infection during pregnancy; and (3) to describe the rate of HCV vertical transmission. METHODS: We prospectively enrolled 145 HCV-positive pregnant women across British Columbia between 2000 and 2003. Participating women were monitored during pregnancy and their infants were followed to assess them for HCV infection. Maternal HCV RNA was assessed close to delivery. RESULTS: Seventy percent of women reported injection drug use as their primary risk factor for HCV acquisition. Observed rates of intrauterine fetal death, preterm delivery, small for gestational age, and low birth weight infants were 3.4%, 17.9%, 11.3%, and 12.5%, respectively, without a significant association with maternal HCV RNA status. The rate of cholestasis was 5.6% in the HCV RNA-positive group (6/108) and 2.8% in the HCV RNA-negative group (1/37) (P = 0.496). Serum alanine aminotransferase levels decreased significantly through pregnancy, and were significantly higher in HCV RNA-positive women than in HCV RNA-negative women after controlling for cholestasis, co-infections, and alcohol consumption. Among the HCV RNA-positive women, the median FIB-4 score was 0.67 (IQR 0.56 to 0.76) in the first trimester, 0.74 (IQR 0.52 to 1.18) in the second trimester, and 0.89 (IQR 0.52 to 1.09) in the third trimester (P = 0.02). The median HCV viral load at delivery was 424 561 IU/mL. The vertical transmission rate was 4.7% in HCV RNA-positive women, with no cases in HCV RNA-negative women. CONCLUSION: Because of the high rates of poor obstetrical outcomes found in this prospective cohort, population-level screening for HCV in pregnancy should be considered.

Objectifs : 1) Décrire les issues obstétricales et néonatales au sein d'une cohorte de femmes infectées par le virus de l'hépatite C (VHC), en comparant des femmes séropositives pour l'ARN du VHC à des femmes séronégatives pour l'ARN du VHC; 2) caractériser les paramètres virologiques et hépatiques associés à l'infection par le VHC pendant la grossesse; et 3) décrire le taux de transmission verticale du VHC. Méthodes : Nous avons sollicité, de manière prospective, la participation de 145 femmes enceintes séropositives pour le VHC provenant des quatre coins de la Colombie-Britannique, entre 2000 et 2003. Les participantes ont fait l'objet d'un suivi pendant la grossesse, tandis que leurs nouveau-nés ont été suivis afin de déterminer la présence ou non d'une infection par le VHC. La présence d'ARN du VHC chez la mère a été évaluée peu avant l'accouchement. Résultats : Soixante-dix pour cent des femmes ont indiqué que la consommation de drogues par injection constituait leur principal facteur de risque d'acquisition du VHC. Les taux constatés de mort fœtale intra-utérine, d'accouchement préterme, d'hypotrophie fœtale et de faible poids à la naissance étaient, respectivement, de 3,4 %, de 17,9 %, de 11,3 % et de 12,5 %, sans association significative avec le statut maternel quant à l'ARN du VHC. Le taux de cholestase était de 5,6 % chez les femmes séropositives pour l'ARN du VHC (6/108) et de 2,8 % chez les femmes séronégatives pour l'ARN du VHC (1/37) (P = 0,496). Les taux sériques d'alanine aminotransférase ont diminué considérablement tout au long de la grossesse et étaient nettement plus élevés chez les femmes séropositives pour l'ARN du VHC que chez les femmes séronégatives pour l'ARN du VHC, à la suite de la neutralisation des effets de la cholestase, des co-infections et de la consommation d'alcool. Chez les femmes séropositives pour l'ARN du VHC, le score FIB-4 médian était de 0,67 (IIQ 0,56 - 0,76) pendant le premier trimestre, de 0,74 (IIQ 0,52 - 1,18) pendant le deuxième trimestre et de 0,89 (IIQ 0,52 - 1,09) pendant le troisième trimestre (P = 0,02). La charge virale médiane en ce qui concerne le VHC au moment de l'accouchement était de 424 561 UI/ml. Le taux de transmission verticale était de 4,7 % chez les femmes séropositives pour l'ARN du VHC; aucun cas n'a été recensé chez les femmes séronégatives pour l'ARN du VHC. Conclusion : Compte tenu des taux élevés de piètres issues obstétricales qui sont constatés au sein de cette cohorte prospective, la mise en œuvre d'un dépistage populationnel du VHC pendant la grossesse devrait être envisagée.

Characterization of the vaginal microbiota of healthy Canadian women through the menstrual cycle.

BACKGROUND: The vaginal microbial community plays a vital role in maintaining women's health. Understanding the precise bacterial composition is challenging because of the diverse and difficult-to-culture nature of many bacterial constituents, necessitating culture-independent methodology. During a natural menstrual cycle, physiological changes could have an impact on bacterial growth, colonization, and community structure. The objective of this study was to assess the stability of the vaginal microbiome of healthy Canadian women throughout a menstrual cycle by using cpn60-based microbiota analysis. Vaginal swabs from 27 naturally cycling reproductive-age women were collected weekly through a single menstrual cycle. Polymerase chain reaction (PCR) was performed to amplify the universal target region of the cpn60 gene and generate amplicons representative of the microbial community. Amplicons were pyrosequenced, assembled into operational taxonomic units, and analyzed. Samples were also assayed for total 16S rRNA gene content and Gardnerella vaginalis by quantitative PCR and screened for the presence of Mollicutes by using family and genus-specific PCR. RESULTS: Overall, the vaginal microbiome of most women remained relatively stable throughout the menstrual cycle, with little variation in diversity and only modest fluctuations in species richness. Microbiomes between women were more different than were those collected consecutively from individual women. Clustering of microbial profiles revealed the expected groupings dominated by Lactobacillus crispatus, Lactobacillus iners, and Lactobacillus jensenii. Interestingly, two additional clusters were dominated by either Bifidobacterium breve or a heterogeneous mixture of nonlactobacilli. Direct G. vaginalis quantification correlated strongly with its pyrosequencing-read abundance, and Mollicutes, including Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum, were detected in most samples. CONCLUSIONS: Our cpn60-based investigation of the vaginal microbiome demonstrated that in healthy women most vaginal microbiomes remained stable through their menstrual cycle. Of interest in these findings was the presence of Bifidobacteriales beyond just Gardnerella species. Bifidobacteriales are frequently underrepresented in 16S rRNA gene-based studies, and their detection by cpn60-based investigation suggests that their significance in the vaginal community may be underappreciated.

Hepatitis C infection among pregnant women in British Columbia: reported prevalence and critical appraisal of current prenatal screening methods.

BACKGROUND: Despite the fact that hepatitis C virus (HCV) is a relatively common infection in Canada, particularly in British Columbia (BC), there is a paucity of information on actual HCV prevalence in pregnant women. At present, pregnant women are only screened if they fit risk criteria, which may result in under-identification of HCV in this population. The purpose of this study was to determine the overall prevalence rate, age and geographic distribution of reported HCV infection among pregnant women in BC, and compare results to a previously conducted anonymous seroprevalence survey. METHODS: Reported HCV prevalence was determined through a confidential database linkage of all prenatal screening results at the Canadian Blood Services (CBS) with all HCV test results at the Provincial Laboratory, from May 2000 to Oct 2002. Data were stratified by age group and geographic location, and subsequently compared to an anonymous prenatal seroprevalence survey conducted in 1994. RESULTS: The overall HCV prevalence rate was 50.3/10,000 (95% CI 46.3-54.6), or 0.5% of the cohort. Prevalence was highest in the northern BC region (66.2/10,000, 95% CI 51.4-85.3) and lowest in the populous suburban region southwest of Vancouver (38.0/10,000, 95% CI 32.3-44.8). Of note, the rate of reported HCV among pregnant women was significantly lower than the anonymous seroprevalence rate: 50.3/10,000 vs. 91.3/10,000 (p < 0.0001). CONCLUSION: Rates of reported HCV among pregnant women were approximately 50% lower than the rates determined by the anonymous seroprevalence survey. Further research is needed to determine the relative merits of the current selective screening policy versus universal prenatal HCV screening in pregnancy.

Ontogeny and individual variation in the adrenocortical response of zebra finch (Taeniopygia guttata) nestlings.

Numerous studies indicate interspecies variation in the ontogeny of the adrenocortical response in birds; however, little is known about the extent of interindividual variation in avian young. Toward this end, we examined the ontogeny and interindividual variation in the adrenocortical response in zebra finch (Taeniopygia guttata) nestlings. We measured baseline and stress-induced total (bound and free) corticosterone, corticosteroid binding globulin capacity, and resulting estimated free corticosterone levels in nestlings of four different ages (days 5, 10, 16, and 21). In addition, we investigated the potential correlates of interindividual variation (brood size and mass). Nestlings at days 5 and 10 post-hatching showed no significant increase in total or free corticosterone levels in response to a standardized handling stress, whereas an adult-like stress response was seen by day 16 post-hatching. There was large interindividual (fivefold) variation in both baseline and stress-induced corticosterone among individual nestlings at any age. We estimate that half of this individual variation in the adrenocortical response could be explained by between-clutch variation (e.g., genetics), while the other half could be explained by other factors such as rearing environment (based on estimated intraclass correlation coefficients). Total baseline corticosterone, but not stress-induced corticosterone, was negatively correlated with fledging mass in this species.

Inadequacy of plasma acyclovir levels at delivery in patients with genital herpes receiving oral acyclovir suppressive therapy in late pregnancy.

OBJECTIVE: Acyclovir therapy in late pregnancy among women with recurrent genital herpes is effective in decreasing genital lesion frequency and subclinical viral shedding rates at delivery, thereby decreasing the need for Caesarean section. Despite good adherence and increased dosing schedules, breakthrough lesions and viral shedding are still observed in some women at or near delivery. Anecdotal evidence suggests that low levels of herpes simplex virus replication at delivery may result in transmission to the neonate. Therefore, defining optimal acyclovir dosing during labour and delivery is warranted. Our objectives were to determine actual maternal and fetal acyclovir levels at delivery, and explore associations between acyclovir levels, duration of labour, and time since last acyclovir dose. METHODS: Twenty-seven patients were prescribed oral acyclovir 400 mg three times daily from 36 weeks' gestation. Cord blood (venous and arterial) and maternal venous blood samples were collected at delivery, and acyclovir levels measured using capillary electrophoresis. Correlations between duration of labour, and time since last acyclovir dose with acyclovir blood levels were calculated. RESULTS: Acyclovir levels were below the published mean steady-state trough value (180 ng/mL) in 52% of venous cord samples, 55% of arterial cord samples, and 36% of maternal samples. There was a significant inverse correlation between the time since last dose and venous cord levels (rs19 = -0.57, P < 0.015), arterial cord levels (rs16 = -0.63, P < 0.01), and maternal acyclovir levels (r10 = -0.69, P < 0.03). CONCLUSION: Oral dosing of acyclovir in women in late pregnancy may result in insufficient levels at delivery to prevent viral shedding. Alternative approaches that incorporate acyclovir dosing through labour, either through oral or intravenous administration, should be evaluated to assess effects on viral shedding.