Stroke Prevention with Hydroxyurea Enabled through Research and Education: A Phase 2 Primary Stroke Prevention Trial in Sub-Saharan Africa.

INTRODUCTION: Stroke is a severe complication of sickle cell anemia (SCA), with devastating sequelae. Transcranial Doppler (TCD) ultrasonography predicts stroke risk, but implementing TCD screening with suitable treatment for primary stroke prevention in low-resource environments remains challenging. SPHERE (NCT03948867) is a prospective phase 2 open-label hydroxyurea trial for SCA in Tanzania. METHODS: After formal training and certification, local personnel screened children 2-16 years old; those with conditional (170-199 cm/s) or abnormal (≥200 cm/s) time-averaged mean velocities (TAMVs) received hydroxyurea at 20 mg/kg/day with dose escalation to maximum tolerated dose (MTD). The primary study endpoint is change in TAMV after 12 months of hydroxyurea; secondary endpoints include SCA-related clinical events, splenic volume and function, renal function, infections, hydroxyurea pharmacokinetics, and genetic modifiers. RESULTS: Between April 2019 and April 2020, 202 children (average 6.8 ± 3.5 years, 53% female) enrolled and underwent TCD screening; 196 were deemed eligible by DNA testing. Most had numerous previous hospitalizations and transfusions, with low baseline hemoglobin (7.7 ± 1.1 g/dL) and %HbF (9.3 ± 5.4%). Palpable splenomegaly was present at enrollment in 49 (25%); average sonographic splenic volume was 103 mL (range 8-1,045 mL). TCD screening identified 22% conditional and 2% abnormal velocities, with hydroxyurea treatment initiated in 96% (45/47) eligible children. CONCLUSION: SPHERE has built local capacity with high-quality research infrastructure and TCD screening for SCA in Tanzania. Fully enrolled participants have a high prevalence of elevated baseline TCD velocities and splenomegaly. SPHERE will prospectively determine the benefits of hydroxyurea at MTD for primary stroke prevention, anticipating expanded access to hydroxyurea treatment across Tanzania.

Effectiveness of system navigation programs linking primary care with community-based health and social services: a systematic review.

BACKGROUND: Fragmented delivery of health and social services can impact access to high-quality, person-centred care. The goal of system navigation is to reduce barriers to healthcare access and improve the quality of care. However, the effectiveness of system navigation remains largely unknown. This systematic review aims to identify the effectiveness of system navigation programs linking primary care with community-based health and social services to improve patient, caregiver, and health system outcomes. METHODS: Building on a previous scoping review, PsychInfo, EMBASE, CINAHL, MEDLINE, and Cochrane Clinical Trials Registry were searched for intervention studies published between January 2013 and August 2020. Eligible studies included system navigation or social prescription programs for adults, based in primary care settings. Two independent reviewers completed study selection, critical appraisal, and data extraction. RESULTS: Twenty-one studies were included; studies had generally low to moderate risk of bias. System navigation models were lay person-led (n = 10), health professional-led (n = 4), team-based (n = 6), or self-navigation with lay support as needed (n = 1). Evidence from three studies (low risk of bias) suggests that team-based system navigation may result in slightly more appropriate health service utilization compared to baseline or usual care. Evidence from four studies (moderate risk of bias) suggests that either lay person-led or health professional-led system navigation models may improve patient experiences with quality of care compared to usual care. It is unclear whether system navigation models may improve patient-related outcomes (e.g., health-related quality of life, health behaviours). The evidence is very uncertain about the effect of system navigation programs on caregiver, cost-related, or social care outcomes. CONCLUSIONS: There is variation in findings across system navigation models linking primary care with community-based health and social services. Team-based system navigation may result in slight improvements in health service utilization. Further research is needed to determine the effects on caregiver and cost-related outcomes.

Altered Maternal Plasma Fatty Acid Composition by Alcohol Consumption and Smoking during Pregnancy and Associations with Fetal Alcohol Spectrum Disorders.

Objective: Polyunsaturated fatty acids are vital for optimal fetal neuronal development. The relationship between maternal alcohol consumption and smoking with third trimester plasma fatty acids were examined and their association with Fetal Alcohol Spectrum Disorders (FASD).Methods: Moderate to heavy alcohol-using and low/unexposed comparison women were recruited during mid-pregnancy from two prenatal clinics in Ukraine. The participants' infants underwent physical and neurobehavioral exams prior to one-year of age and classified as having FASD by maternal alcohol consumption and neurobehavioral scores. A subset of mother-child pairs was selected representing three groups of cases and controls: Alcohol-Exposed with FASD (AE-FASD, n = 30), Alcohol-Exposed Normally Developing (AE-ND, n = 33), or Controls (n = 46). Third trimester maternal plasma samples were analyzed for fatty acids and levels were compared across groups.Results: The percent of C18:0 (p < 0.001), arachidonic acid (AA, C20:4n-6, p = 0.017) and C22:5n-6 (p = 0.001) were significantly higher in AE-FASD women than controls or AE-ND women. Alcohol-exposed women who smoked had lower C22:5n-3 (p = 0.029) and docosahexaenoic acid (DHA, C22:6n-3, p = 0.005) and higher C22:5n-6 (p = 0.013) than women consuming alcohol alone or abstainers.Conclusion: Alterations in fatty acid profiles were observed in moderate to heavy alcohol-consuming mothers with infants classified with FASD compared to alcohol-exposed normally developing infants or controls.

Vitamin D Deficiency in Pregnant Ukrainian Women: Effects of Alcohol Consumption on Vitamin D Status.

OBJECTIVE: Heavy alcohol consumption can alter vitamin D status; however, the relationships between alcohol consumption and vitamin D concentrations in pregnant women have not been well studied. The aim of this study was to investigate the vitamin D status in a population of alcohol-exposed (N = 180) and low/unexposed control (N = 179) Ukrainian pregnant women. METHODS: Women who attended prenatal care facilities in 2 regions of Ukraine (Rivne and Khmelnytsky) for a routine prenatal visit were screened for the study. At the time of enrollment (20.4 ± 7.0 weeks of gestation), blood samples and alcohol consumption data (during a typical week around conception and the most recent 2 weeks) were collected. Vitamin D status was assessed by 25-hydroxyvitamin D [25(OH)D] concentrations. RESULTS: A high prevalence of suboptimal vitamin D status in pregnant Ukrainian women was observed. Overall, 50.1% and 33.4% of the women were classified as vitamin D deficient [25(OH)D < 20 ng/mL] or insufficient [25(OH)D ≥ 20 ng/mL and ≤30 ng/mL], respectively, based on 2011 Endocrine Society guidelines. Alcohol-exposed women had significantly lower 25(OH)D concentrations than low/unexposed women in Spring (p = 0.006) and Winter (p = 0.022). When vitamin D concentrations were grouped into sunny season (Summer + Fall) compared to not sunny season (Winter + Spring), there was a significant ethanol by season interaction (p = 0.0028), with alcohol-drinking women having lower circulating vitamin D compared to low/unexposed women in seasons of low sun availability. CONCLUSIONS: These data suggest that when vitamin D concentrations are generally low (e.g., during seasons of low sun availability), alcohol consumption during pregnancy has a negative impact on vitamin D status.

Analysis of head impact exposure and brain microstructure response in a season-long application of a jugular vein compression collar: a prospective, neuroimaging investigation in American football.

BACKGROUND: Historical approaches to protect the brain from outside the skull (eg, helmets and mouthpieces) have been ineffective in reducing internal injury to the brain that arises from energy absorption during sports-related collisions. We aimed to evaluate the effects of a neck collar, which applies gentle bilateral jugular vein compression, resulting in cerebral venous engorgement to reduce head impact energy absorption during collision. Specifically, we investigated the effect of collar wearing during head impact exposure on brain microstructure integrity following a competitive high school American football season. METHODS: A prospective longitudinal controlled trial was employed to evaluate the effects of collar wearing (n=32) relative to controls (CTRL; n=30) during one competitive football season (age: 17.04±0.67 years). Impact exposure was collected using helmet sensors and white matter (WM) integrity was quantified based on diffusion tensor imaging (DTI) serving as the primary outcome. RESULTS: With similar overall g-forces and total head impact exposure experienced in the two study groups during the season (p>0.05), significant preseason to postseason changes in mean diffusivity, axial diffusivity and radial diffusivity in the WM integrity were noted in the CTRL group (corrected p<0.05) but not in the collar group (p>0.05). The CTRL group demonstrated significantly larger preseason to postseason DTI change in multiple WM regions compared with the collar group (corrected p<0.05). DISCUSSION: Reduced WM diffusivity alteration was noted in participants wearing a neck collar after a season of competitive football. Collar wearing may have provided a protective effect against brain microstructural changes after repetitive head impacts. TRIAL REGISTRATION NUMBER: NCT02696200.

Towards algorithm auditing: managing legal, ethical and technological risks of AI, ML and associated algorithms.

-Business reliance on algorithms is becoming ubiquitous, and companies are increasingly concerned about their algorithms causing major financial or reputational damage. High-profile cases include Google's AI algorithm for photo classification mistakenly labelling a black couple as gorillas in 2015 (Gebru 2020 In The Oxford handbook of ethics of AI, pp. 251-269), Microsoft's AI chatbot Tay that spread racist, sexist and antisemitic speech on Twitter (now X) (Wolf et al. 2017 ACM Sigcas Comput. Soc. 47, 54-64 (doi:10.1145/3144592.3144598)), and Amazon's AI recruiting tool being scrapped after showing bias against women. In response, governments are legislating and imposing bans, regulators fining companies and the judiciary discussing potentially making algorithms artificial 'persons' in law. As with financial audits, governments, business and society will require algorithm audits; formal assurance that algorithms are legal, ethical and safe. A new industry is envisaged: Auditing and Assurance of Algorithms (cf. data privacy), with the remit to professionalize and industrialize AI, ML and associated algorithms. The stakeholders range from those working on policy/regulation to industry practitioners and developers. We also anticipate the nature and scope of the auditing levels and framework presented will inform those interested in systems of governance and compliance with regulation/standards. Our goal in this article is to survey the key areas necessary to perform auditing and assurance and instigate the debate in this novel area of research and practice.

Vitamin D and maternal and child health: overview and implications for dietary requirements.

The essentiality of vitamin D for normal growth and development has been recognized for over 80 years, and vitamin D fortification programs have been in place in the United States for more than 70 years. Despite the above, vitamin D deficiency continues to be a common finding in certain population groups. Vitamin D deficiency has been suggested as a potential risk factor for the development of preeclampsia, and vitamin D deficiency during infancy and early childhood is associated with an increased risk for numerous skeletal disorders, as well as immunological and vascular abnormalities. Vitamin D deficiency can occur through multiple mechanisms including the consumption of diets low in this vitamin and inadequate exposure to environmental ultraviolet B rays. The potential value of vitamin D supplementation in high-risk pregnancies and during infancy and early childhood is discussed. Currently, there is vigorous debate concerning what constitutes appropriate vitamin D intakes during early development as exemplified by differing recommendations from the Institute of Medicine Dietary Reference Intake report and recent recommendations by the Endocrine Society. As is discussed, a major issue that needs to be resolved is what key biological endpoint should be used when making vitamin D recommendations for the pregnant woman and her offspring.

Evaluating the impact of engaging older adults and service providers as research partners in the co-design of a community mobility-promoting program: a mixed methods developmental evaluation study.

BACKGROUND: Increasingly researchers are partnering with citizens and communities in research; less is known about research impacts of this engagement. EMBOLDEN is an evidence-informed, mobility-promoting intervention for older adults co-designed by a 26-person Strategic Guiding Council (SGC) of health/social service providers and older adult citizens. This study evaluated research partners' perceptions of engagement strategies, the engagement context, strengths, areas for improvement, as well as the impacts of the guiding council on older-adult identified priority areas. METHODS: This study was guided by developmental evaluation, working in partnership with four older adult SGC members who helped to set evaluation priorities, decide methods, and adapt patient-centred evaluation tools. Data sources included a questionnaire, focus groups and document analysis of meeting notes from 16 SGC meetings that took place between December 2019 and February 2022. A thematic approach to analysis guided the coding of focus group transcripts and SGC meeting notes. Convergent mixed methods guided the integration and presentation of qualitative and quantitative data sources in a joint display of evaluation results. RESULTS: Of 26 SGC members, nine completed the evaluation squestionnaire, and five participated in focus groups. Around two thirds of the SGC commonly attended each meeting. EMBOLDEN's SGC was structured to include a diverse group (across gender, ethnicity and discipline) of older adults and service providers, which was perceived as a strength. Engagement processes were perceived as inclusive and well-facilitated, which stimulated discussion at meetings. Advantages and disadvantages of engaging with the SGC virtually, as compared to in-person (as was the case for the first 3 SGC meetings) were also discussed. Impacts of the SGC were identified across preparatory, execution phase and translational stages of research. Impacts of SGC involvement on members were also described. CONCLUSION: Older adult research partners played an important role designing, implementing, and evaluating co-design approaches in this study. Older adults and service providers can make important contributions to the design, delivery and sharing results of health research through their lived expertise and connections to community. This project contributes to the growing field of citizen and community engagement in research by offering a participatory approach to engagement evaluation that considers diversity, satisfaction, and impact.

It is becoming common for researchers to ask patients and caregivers to become involved with their studies as partners. By partnering with people who have first-hand experience with a condition, researchers hope their studies will be more relevant, run efficiently and have more impact than studies designed by researchers alone. Over the last twenty years, there has been a significant increase in the number of published papers that involve patients and caregivers, but few papers mention what changed because of this involvement. Researchers need to know the best ways to involve patients and caregivers and the impact of doing so.This study aimed to find out how a council of older adults (OAs) and service providers (SPs) impacted a study about collaboratively designing and testing a mobility intervention. This study aimed to find out how council members felt about their involvement in this study, by asking them what went well and what could have been improved.This study used a questionnaire, focus groups and analyzed council meeting notes to inform this study. Four OA council members helped design the study, decide research methods, and adapt wording of questions (focus groups, questionnaire). Between 19% and 35% of council members completed evaluation activities. They felt the study strengths were the diversity of the council, and a welcoming environment for discussion. The council impacted how the study was designed, carried out and how results were shared. Results from this study can improve patient partnership engagement, experiences, and impacts in future studies.

Association of serum folate levels during pregnancy and prenatal depression.

OBJECTIVE: To evaluate the association between serum folate levels during pregnancy and prenatal depression and the extent to which obesity may modify this relationship. METHODS: This secondary data analysis leveraged data from a previous study of pregnant Kaiser Permanente Northern California participants who completed a survey and provided a serum sample between 2011 and 2013. Serum folate was assessed using the Center for Disease Control's Total Folate Serum/Whole Blood Microbiological Assay Method. A score of 15 or greater on the Center for Epidemiologic Studies Depression Scale was defined as prenatal depression. We used Poisson regression to estimate risk of prenatal depression given prenatal serum folate status (low/medium tertiles vs. high tertile) in the full sample and in subsamples of women with pre-pregnancy body mass index in the (a) normal range and (b) overweight/obese range. RESULTS: Of the sample, 13% had prenatal depression. Combined low/medium folate tertiles was associated with prenatal depression (adjusted relative risk [aRR] = 1.97, 95% confidence interval [CI]: 0.93-4.18), although results did not reach statistical significance. This relationship was stronger among women with overweight/obesity than women with normal weight (aRR: 2.61, 95% CI: 1.01-6.71 and aRR: 1.50, 95% CI: 0.34-6.66, respectively). CONCLUSION: Results suggest an association between lower pregnancy folate levels and prenatal depression that may be stronger among women with overweight or obesity. Future studies need to clarify the temporal sequence of these associations.

Pediatric physical therapists' use of support walkers for children with disabilities: a nationwide survey.

PURPOSE: This study investigated pediatric physical therapists' use of support walkers (SWs) for children with disabilities. METHODS: An 8-page survey was mailed to 2500 randomly selected members of the Section on Pediatrics of the American Physical Therapy Association. Respondents to the survey included 513 pediatric physical therapists who were users of SWs. Descriptive statistics were calculated and themes were analyzed. RESULTS: Several SWs were reported as used most often to improve gait, mobility, participation at school, and interaction with peers. Use commonly included a month trial before purchase and 9 sessions of physical therapy to train a child for use in school. Reasons given for the use of SWs were improving impairments, functional limitations, and participation with peers. CONCLUSIONS: Pediatric physical therapists use SWs to increase postural control, mobility, and children's participation in school.

Main Concept, Sequencing, and Story Grammar Analyses of Cinderella Narratives in a Large Sample of Persons with Aphasia.

Recently, a multilevel analytic approach called Main Concept, Sequencing, and Story Grammar (MSSG) was presented along with preliminary normative information. MSSG analyses leverage the strong psychometrics and rich procedural knowledge of both main concept analysis and story grammar component coding, complementing it with easy-to-obtain sequencing information for a rich understanding of discourse informativeness and macrostructure. This study is the next critical step for demonstrating the clinical usefulness of MSSG's six variables (main concept composite, sequencing, main concept+sequencing, essential story grammar components, total episodic components, and episodic complexity) for persons with aphasia (PWAs). We present descriptive statistical information for MSSG variables for a large sample of PWAs and compare their performance to a large sample of persons not brain injured (PNBIs). We observed significant differences between PWAs and PNBIs for all MSSG variables. These differences occurred at the omnibus group level and for each aphasia subtype, even for PWAs with very mild impairment that is not detected with standardized aphasia assessment. Differences between PWAs and PNBIs were also practically significant, with medium to large effect sizes observed for nearly all aphasia subtypes and MSSG variables. This work deepens our understanding of discourse informativeness and macrostructure in PWAs and further develops an efficient tool for research and clinical use. Future research should investigate ways to expand MSSG analyses and to improve sensitivity and specificity.

Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial.

BACKGROUND: Epidemiological data shows low dietary magnesium(Mg) may be related to incidence and progression of asthma. OBJECTIVE: To determine if long term(6.5 month) treatment with oral Mg would improve asthma control and increase serum measures of Mg status in men and women with mild-to-moderate asthma. SUBJECTS: 55 males and females aged 21 to 55 years with mild to moderate asthma according to the 2002 National Heart, Lung, and Blood Institute(NHLBI) and Asthma Education and Prevention Program(NAEPP) guidelines and who used only beta-agonists or inhaled corticosteroids(ICS) as asthma medications were enrolled. DESIGN: Subjects were randomly assigned to consume 340 mg(170 mg twice a day) of Mg or a placebo for 6.5 months. MEASUREMENTS: Multiple measures of Mg status including serum, erythrocyte, urine, dietary, ionized and IV Mg were measured. OBJECTIVE: markers of asthma control were: methacholine challenge test(MCCT) and pulmonary function test(PFT) results. Subjective validated questionnaires on asthma quality of life(AQLQ) and control(ACQ) were completed by participants. Markers of inflammation, including c-reactive protein(CRP) and exhaled nitric oxide(eNO) were determined. RESULTS: The concentration of methacholine required to cause a 20% drop in forced expiratory volume in in minute(FEV(1)) increased significantly from baseline to month 6 within the Mg group. Peak expiratory flow rate(PEFR) showed a 5.8% predicted improvement over time(P = 0.03) in those consuming the Mg. There was significant improvement in AQLQ mean score units(P < 0.01) and in overall ACQ score only in the Mg group(P = 0.05) after 6.5 months of supplementation. Despite these improvements, there were no significant changes in any of the markers of Mg status. CONCLUSION: Adults who received oral Mg supplements showed improvement in objective measures of bronchial reactivity to methacholine and PEFR and in subjective measures of asthma control and quality of life.

Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development.

A large body of evidence supports the concept that human pregnancy outcome is significantly influenced by the nutritional status of the mother. The consumption of "poor diets" has been associated with an increased risk for pregnancy complications, including gross structural birth defects, prematurity, low birth weight, and an increased risk for neurobehavioral and immunological abnormalities after birth. Forty-four years ago, zinc deficiency in mammals was shown to be teratogenic. Maternal zinc deficiency produces effects ranging from infertility and embryo/fetal death, to intrauterine growth retardation and teratogenesis. Postnatal complications of maternal zinc deficiency can also occur, and include behavioral abnormalities, impaired immunocompetence, and an elevated risk for high blood pressure in the offspring. It has been suggested that developmental zinc deficiency in humans can present a significant challenge to the conceptus, increasing the risk for numerous defects. Developmental zinc deficiency can occur through multiple pathways, and the concept that acute phase response-induced changes in maternal zinc metabolism may be a common cause of embryonic and fetal zinc deficiency is presented. Potential mechanisms underlying the teratogenic effects of zinc deficiency are reviewed. The potential value of maternal zinc supplementation in high risk pregnancies is discussed.

Safety coaches in radiology: decreasing human error and minimizing patient harm.

Successful programs to improve patient safety require a component aimed at improving safety culture and environment, resulting in a reduced number of human errors that could lead to patient harm. Safety coaching provides peer accountability. It involves observing for safety behaviors and use of error prevention techniques and provides immediate feedback. For more than a decade, behavior-based safety coaching has been a successful strategy for reducing error within the context of occupational safety in industry. We describe the use of safety coaches in radiology. Safety coaches are an important component of our comprehensive patient safety program.

Implementing an advance emergency contraception policy: what happens in the real world?

CONTEXT: Advance provision of emergency contraception increases the likelihood of its use, yet little is known about the factors that influence successful implementation of an advance provision policy in publicly funded family planning clinics. METHODS: Data on knowledge of, attitudes toward and use of emergency contraception were collected from 211 patients attending four Title X-funded clinics in Pennsylvania in 2001-2002. In addition, 22 staff from the four clinics were interviewed regarding barriers to and facilitators of advance provision in 2004-2005, and 111 staff from 46 clinics completed related surveys in 2005. Qualitative data underwent content analysis, and frequencies and bivariate associations between variables were calculated for the survey data. RESULTS: Most patients said they would use emergency contraception (80%) and believed it should be easy to obtain (93%), although 46% thought it is a form of abortion. Patients' familiarity with the method, attitudes toward it and self-efficacy regarding its use were not associated with most demographic or reproductive health characteristics. While nearly all interviewed staff endorsed routine advance provision, only about half of survey respondents offered it "very often" at patients' initial or annual visits. Barriers to advance provision included staff prejudgment of patients' needs and ability to use the method, time constraints and inefficiencies in clinic procedures. CONCLUSIONS: Strategies that may facilitate advance provision of emergency contraception include emphasizing the need for staff to offer it during all patient visits, providing patient-friendly information and streamlining clinic procedures.

Perspectives of African American, Amish, Appalachian And Latina women on breast and cervical cancer screening: implications for cultural competence.

Low-income and minority women are less likely to be screened for breast and cervical cancer and less likely than others to be diagnosed at an early stage in the cancer's growth. We consulted women and providers to understand how social, economic, and health care environments affect screening among African American, Amish, Appalachian, and Latina women, and to outline possible solutions. Women participated in 31 focus groups. Providers completed a mail survey (n=168) and follow-up interviews (n=12). We identified barriers women face: not always following recommendations; feeling intimidated during appointments; having incorrect information about risks, screening guidelines, and programs; and receiving information in ways they cannot understand or accept. Women indicated a strong desire for accurate information and, like the providers, identified strategies for reducing barriers to screening. In the terms of a social ecological model, our results point to three avenues along which to approach cultural competence: 1) policy, 2) health care provision, and 3) clinical care.

Mild Jugular Compression Collar Ameliorated Changes in Brain Activation of Working Memory after One Soccer Season in Female High School Athletes.

Recent neuroimaging studies have suggested that repetitive subconcussive head impacts, even after only one sport season, may lead to pre- to post-season structural and functional alterations in male high school football athletes. However, data on female athletes are limited. In the current investigation, we aimed to (1) assess the longitudinal pre- to post-season changes in functional MRI (fMRI) of working memory and working memory performance, (2) quantify the association between the pre- to post-season change in fMRI of working memory and the exposure to head impact and working memory performance, and (3) assess whether wearing a neck collar designed to reduce intracranial slosh via mild compression of the jugular veins can ameliorate the changes in fMRI brain activation observed in the female high school athletes who did not wear collars after a full soccer season. A total of 48 female high school soccer athletes (age range: 14.00-17.97 years) were included in the study. These athletes were assigned to the non-collar group (n = 21) or to the collar group (n = 27). All athletes undewent MRI at both pre-season and post-season. In each session, a fMRI verbal N-Back task was used to engage working memory. A significant pre- to post-season increase in fMRI blood oxygen level dependent (BOLD) signal was demonstrated when performing the N-back working memory task in the non-collar group but not in the collar group, despite the comparable exposure to head impacts during the season between the two groups. The collar group demonstrated significantly smaller pre- to post-season change in fMRI BOLD signal than the non-collar group, suggesting a potential protective effect from the collar device. Significant correlations were also found between the pre- to post-season increase in fMRI brain activation and the decrease in task accuracy in the non-collar group, indicating an association between the compensatory mechanism in underlying neurophysiology and the alteration in the behavioral outcomes.

Low nitric oxide: a key factor underlying copper-deficiency teratogenicity.

Copper (Cu)-deficiency-induced teratogenicity is characterized by major cardiac, brain, and vascular anomalies; however, the underlying mechanisms are poorly understood. Cu deficiency decreases superoxide dismutase activity and increases superoxide anions, which can interact with nitric oxide (NO), reducing the NO pool size. Given the role of NO as a developmental signaling molecule, we tested the hypothesis that low NO levels, secondary to Cu deficiency, represent a developmental challenge. Gestation day 8.5 embryos from Cu-adequate (Cu+) or Cu-deficient (Cu-) dams were cultured for 48 h in Cu+ or Cu- medium, respectively. We report that NO levels were low in conditioned medium from Cu-/Cu- embryos and yolk sacs, compared to Cu+/Cu+ controls under basal conditions and with NO synthase (NOS) agonists. The low NO production was associated with low endothelial NOS phosphorylation at serine 1177 and cyclic guanosine-3',5'-monophosphate (cGMP) concentrations in the Cu-/Cu- group. The altered NO levels in Cu-deficient embryos are functionally significant, as the administration of the NO donor DETA/NONOate increased cGMP and ameliorated embryo and yolk sac abnormalities. These data support the concept that Cu deficiency limits NO availability and alters NO-dependent signaling, which contributes to abnormal embryo and yolk sac development.

Characteristics associated with emergency contraception use by family planning patients: a prospective cohort study.

CONTEXT: Little is known about how written family planning clinic policy regarding emergency contraception, as well as personal characteristics, behaviors and attitudes, may influence a woman to use emergency contraception. METHODS: Between June 2001 and July 2002, women attending publicly funded family planning clinics in Pennsylvania were enrolled in an 18-month longitudinal study. Half attended clinics with a policy of offering emergency contraception in advance; the remainder had only emergent access to the drug. After providing baseline data, women completed monthly automated phone surveys about recent sexual activity, contraceptive use and attitudes toward pregnancy. Characteristics associated with recent use of emergency contraception were examined using multivariate logistic regression. RESULTS: Responses to 3,700 phone surveys from 729 women showed that 25% of those who attended clinics offering advance access used emergency contraception at least once during the study, compared with 8% who attended emergent access clinics. Women attending advance access clinics had significantly elevated odds of having used emergency contraception in the past month (odds ratio, 2.6). Other characteristics positively associated with the likelihood of recent emergency contraception use were familiarity with the drug, having a new sex partner and having unprotected sex at least once (2.0 each); negative feelings toward pregnancy (1.4); and using condoms as one's main contraceptive method (1.8). CONCLUSIONS: In addition to discussing and offering advance emergency contraception, providers should further explore specific behaviors and attitudes associated with emergency contraception use.

Abnormal development and increased 3-nitrotyrosine in copper-deficient mouse embryos.

Copper-deficient rat embryos are characterized by brain and heart anomalies, low superoxide dismutase activity, and high superoxide anion concentrations. One consequence of increased superoxide anions can be the formation of peroxynitrite, a strong biological oxidant. To investigate developmentally important features of copper deficiency, GD 8.5 mouse embryos from copper-adequate and copper-deficient dams were cultured in media that were adequate or deficient in copper. After 48 h, copper-deficient embryos exhibited brain and heart anomalies, and a high incidence of yolk sac vasculature abnormalities compared to controls. Immunohistochemistry of 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine for lipid and DNA damage, respectively, was similar between groups. In contrast, 3-nitrotyrosine, taken as a measure of protein nitration, was markedly higher in the neuroepithelium of the anterior neural tube of copper-deficient embryos than in controls. Repletion of copper-deficient media with copper, or supplementation with copper-zinc superoxide dismutase, Tiron, or glutathione peroxidase did not ameliorate the abnormal development, but did decrease 3-nitrotyrosine in neuroepithelium of copper-deficient embryos. These data support the concept that while copper deficiency compromises oxidant defense and increases protein nitration, additional mechanisms, e.g., altered nitric oxide metabolism may contribute to copper-deficiency-induced teratogenesis.