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Background and Objective: To assess the public's perception of pharmacists' involvement and role in cardiovascular disease prevention and management. Methods: A computer-assisted telephone interview of 505 households was conducted. The survey was administered to metropolitan, rural and remote residents over the age of 30 years. The interview had questions on the patient's general satisfaction with the quality of service provided by their regular community pharmacy, including factors such as location, professionalism, prices, product range and knowledge of the staff. The participants were asked if they thought pharmacists were capable of providing screening, testing and drug prescribing services for blood pressure and cholesterol, and how likely they would be to use these services through a pharmacy. The interview also included questions on how likely this person would be to seek advice on lifestyle changes and medications from various health professionals, including pharmacists. Results: The majority (97%) were satisfied with the service provided at their regular pharmacy. Those surveyed agreed or strongly agreed that pharmacists are capable of providing screening or testing for raised blood pressure (52%) and diabetes (51%), with a minority (38%) agreeing that pharmacists are capable of testing for raised cholesterol. The pharmacist's role with perceived highest capability by those surveyed was in providing advice on how to take medicines properly, with 90% of respondents willing to seek this advice from their pharmacist. A limited role by pharmacists was seen in the diagnosis of CVD and prescribing medications. In relation to the prevention of CVD, even though 76% of respondents believed that pharmacists are capable of providing advice on lifestyle changes (e.g. weight loss, smoking and alcohol intake), only 8% of current or past smokers had sought assistance to give up smoking at their pharmacy and while 69% of all respondents had sought help with weight control, only 3% of these had looked towards their pharmacy for assistance. Conclusion: There was belief by those Australians surveyed that community pharmacists are capable of providing screening for hypertension and diabetes. Through these services and in conjunction with counselling on CVD risk reduction, pharmacists may play an important role in the reduction of CVD, ultimately improving public health and decreasing the burden on Australia's health care system. However, at present pharmacists are not being fully utilized to deliver health promotion advice and contribute to the prevention of CVD. [ABSTRACT FROM AUTHOR]

Abstract Background The human psoriasin (S100A7) gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/psoriasin in skin inflammation and mammary tumorigenesis. Methods On the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin gene expression (measured by RT-PCR and in-situ hybridization) with those of human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine ortholog of human psoriasin/S100A7. Results Although mouse S100A7/psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene. Conclusion These observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression.

Abstract Background Psoriasin has been identified as a gene that is highly expressed in pre-invasive breast cancer, but is often downregulated with breast cancer progression. It is currently unknown whether psoriasin influences epithelial cell malignancy directly or by affecting the surrounding environment. However the protein is found in the nucleus, cytoplasm as well as extracellularly. In the present study we have sought to identify potential psoriasin-binding proteins and to describe their expression profile in breast tumors. Methods The yeast two-hybrid method was used to identify potential binding partners for psoriasin. The interaction of psoriasin with RanBPM was confirmed in-vitro by co-immunoprecipitation. The expression of RanBPM and psoriasin was measured by RT-PCR in a series of breast cell lines, breast tumors and primary lymphocytes. Results We have identified RanBPM as an interacting protein by the yeast two-hybrid assay and confirmed this interaction in-vitro by co-immunoprecipitation. RT-PCR analysis of RanBPM mRNA expression in cell lines (n = 13) shows that RanBPM is widely expressed in different cell types and that expression is higher in tumor than in normal breast epithelial cell lines. RanBPM expression can also be induced in peripheral blood mononuclear cells by treatment with PHA. RanBPM mRNA is also frequently expressed in invasive breast carcinomas (n = 64) and a higher psoriasin/RanBPM ratio is associated with both ER negative (p < 0.0001) and PR negative status (p < 0.001), and inflammatory cell infiltrates (p < 0.0001) within the tumor. Conclusions These findings support the hypothesis that psoriasin may interact with RanBPM and this may influence both epithelial and stromal cells and thus contribute to breast tumor progression.

Early adversity increases risk for child mental health difficulties. Stressors in the home environment (e.g., parental mental illness, household socioeconomic challenges) may be particularly impactful. Attending out-of-home childcare may buffer or magnify negative effects of such exposures. Using a longitudinal observational design, we leveraged data from the NIH Environmental influences on Child Health Outcomes Program to test whether number of hours in childcare, defined as 1) any type of nonparental care and 2) center-based care specifically, was associated with child mental health, including via buffering or magnifying associations between early exposure to psychosocial and socioeconomic risks (age 0-3 years) and later internalizing and externalizing symptoms (age 3-5.5 years), in a diverse sample of N = 2,024 parent-child dyads. In linear regression models, childcare participation was not associated with mental health outcomes, nor did we observe an impact of childcare attendance on associations between risk exposures and symptoms. Psychosocial and socioeconomic risks had interactive effects on internalizing and externalizing symptoms. Overall, the findings did not indicate that childcare attendance positively or negatively influenced child mental health and suggested that psychosocial and socioeconomic adversity may need to be considered as separate exposures to understand child mental health risk in early life.

Background: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample., Methods: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy., Results: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen., Conclusion: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children., Impact: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Executive function, which develops rapidly in childhood, enables problem-solving, focused attention, and planning. Animal models describe executive function decrements associated with ambient air pollution exposure, but epidemiologic studies are limited., Methods: We examined associations between early childhood air pollution exposure and school-aged executive function in 1235 children from three US pregnancy cohorts in the ECHO-PATHWAYS Consortium. We derived point-based residential exposures to ambient particulate matter ≤2.5 µm in aerodynamic diameter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) at ages 0-4 years from spatiotemporal models with a 2-week resolution. We assessed executive function across three domains, cognitive flexibility, working memory, and inhibitory control, using performance-based measures and calculated a composite score quantifying overall performance. We fitted linear regressions to assess air pollution and child executive function associations, adjusting for sociodemographic characteristics, maternal mental health, and health behaviors, and examined modification by child sex, maternal education, and neighborhood educational opportunity., Results: In the overall sample, we found hypothesized inverse associations in crude but not adjusted models. Modified associations between NO 2 exposure and working memory by neighborhood education opportunity were present ( Pinteraction = 0.05), with inverse associations more pronounced in the "high" and "very high" categories. Associations of interest did not differ by child sex or maternal education., Conclusion: This work contributes to the evolving science regarding early-life environmental exposures and child development. There remains a need for continued exploration in future research endeavors, to elucidate the complex interplay between natural environment and social determinants influencing child neurodevelopment., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited., Methods: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture., Results: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident., Conclusion: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases., Competing Interests: Declaration of competing interest All authors have confirmed that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Transfusion-associated circulatory overload (TACO) is a largely preventable transfusion complication that results in significant morbidity and mortality. Cancers, related treatments, and comorbidities are among the factors that can predispose patients to TACO, but currently there are limited data on this topic in the literature., Methods: We collected data retrospectively from the electronic health records of 93 adult patients with cancer who met Centers for Disease Control and Prevention (CDC) criteria for TACO from July 1, 2019, through October 31, 2020. The parameters we studied included demographics, comorbidities, treatment modalities, transfusion practices, and outcomes. We summarized data by means and ranges for continuous variables, and proportions for categorical variables., Results: During the study period, the incidence of TACO among oncology patients was 0.84 per 1000 transfusions (95% CI, 0.68-1.02), representing 6.6% of all reactions. This percentage is high, compared with 1%-6% among other populations. Unique characteristics such as hematology malignancy (75.3%), receipt of cardiotoxic chemotherapy (87.1%), pneumonia (57.0%), preexisting oxygen use (59.1%), dyspnea (62.4%), hypertension (55.9%), renal insufficiency (46.2%), daily use of corticosteroids (43.0%), daily use of diuretics (40.9%), daily use of beta-blockers (36.6%), and elevated NT-proBNP (33.3%) were frequently observed in these group of oncology patients., Conclusions: Our study indicates that oncology patients have unique factors that may lead to diagnosis of TACO. Developing appropriate guidelines that apply to oncology patients, in addition to those set forth by the CDC, should be considered. Implementation by ordering healthcare providers of a tools that can predict TACO can help in early recognition and mitigation of TACO., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Population studies support the adverse associations of air pollution exposures with child behavioral functioning and cognitive performance, but few studies have used spatiotemporally resolved pollutant assessments., Objectives: We investigated these associations using more refined exposure assessments in 1,967 mother-child dyads from three U.S. pregnancy cohorts in six cities in the ECHO-PATHWAYS Consortium., Methods: Pre- and postnatal nitrogen dioxide ( NO 2 ) and particulate matter (PM) ≤ 2.5 μ m in aerodynamic diameter ( PM 2.5 ) exposures were derived from an advanced spatiotemporal model. Child behavior was reported as Total Problems raw score using the Child Behavior Checklist at age 4-6 y. Child cognition was assessed using cohort-specific cognitive performance scales and quantified as the Full-Scale Intelligence Quotient (IQ). We fitted multivariate linear regression models that were adjusted for sociodemographic, behavioral, and psychological factors to estimate associations per 2-unit increase in pollutant in each exposure window and examined modification by child sex. Identified critical windows were further verified by distributed lag models (DLMs)., Results: Mean NO 2 and PM 2.5 ranged from 8.4  to  9.0  ppb and 8.4  to  9.1   μ g / m 3 , respectively, across pre- and postnatal windows. Average child Total Problems score and IQ were 22.7 [standard deviation (SD): 18.5] and 102.6 (SD: 15.3), respectively. Children with higher prenatal NO 2 exposures were likely to have more behavioral problems [ β : 1.24; 95% confidence interval (CI): 0.39, 2.08; per 2  ppb NO 2 ], particularly NO 2 in the first and second trimester. Each 2 - μ g / m 3 increase in PM 2.5 at age 2-4 y was associated with a 3.59 unit (95% CI: 0.35, 6.84) higher Total Problems score and a 2.63 point (95% CI: - 5.08 , - 0.17 ) lower IQ. The associations between PM 2.5 and Total Problems score were generally stronger in girls. Most predefined windows identified were not confirmed by DLMs., Discussion: Our study extends earlier findings that have raised concerns about impaired behavioral functioning and cognitive performance in children exposed to NO 2 and PM 2.5 in utero and in early life. https://doi.org/10.1289/EHP10248.

Background: Many children with autism and intellectual disability (ID) experience executive functioning (EF) difficulties. However, there is minimal research on EF skills in children with autism, ID, and co-occurring autism/ID in early childhood., Aims: To address this gap in the research, we evaluated EF profiles using the BRIEF-P among early childhood children (2-5 years of age) with autism, ID, and co-occurring autism/ID., Method and Procedures: Participants in the current study were 87 children between the ages of 24 and 71 months (M = 46.8, SD = 12.7) diagnosed with autism (n = 24, 27.6 %), ID (n = 23, 26.4 %), or co-occurring autism/ID (n = 40, 46.0 %) that completed a comprehensive psychological evaluation at a university development center. We used a mixed Analysis of Variance (ANOVA) and between- and within-subjects ANOVAs as follow-up analyses., Outcomes and Results: Results suggested that early childhood children with autism, ID, and autism/ID may have unique EF skill profiles. Children with ID exhibited the most significant EF impairments and children with autism had the least. Working memory was the most impaired EF domain across all diagnostic groups., Conclusions and Implications: Overall, our findings show that early childhood children with autism, ID, and autism/ID exhibit difficulties in EF skills. Children with ID exhibit the most significant EF impairments whereas children with autism show the least. However, regardless of diagnosis, working memory is the most impaired EF skill., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Substantial inter-individual discrepancies exist in both therapeutic effectiveness and adverse effects of antidepressant and antipsychotic medications, which can, in part, be explained by genetic variation. Here, we searched the Pharmacogenomics Knowledge Base for gene-antidepressant and gene-antipsychotic pairs with the highest level of evidence. We then extracted and compared the associated prescribing recommendations for these pairs developed by the Clinical Pharmacogenomics Implementation Consortium, the Dutch Pharmacogenetics Working Group or approved product labels in the US, Canada, Europe, and Asia. Finally, we highlight key economical, educational, regulatory, and ethical issues that, if not appropriately considered, can hinder the implementation of these recommendations in clinical practice. Our review indicates that evidence-based guidelines are available to assist with the implementation of pharmacogenetic-guided antidepressant and antipsychotic prescribing, although the maximum impact of these guidelines on patient care will not be realized until key barriers are minimized or eliminated., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Vitamin D is critical to embryonic neuronal differentiation and other developmental processes that may affect future neurocognitive function. However, observational studies have found inconsistent associations between gestational vitamin D and neurocognitive outcomes., Objectives: We examined the association of gestational 25-hydroxyvitamin D [25(OH)D] with children's IQ at 4-6 y, and explored whether associations differed by race., Methods: This study used data from the CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early Childhood) cohort. Between 2006 and 2011, CANDLE recruited 1503 women in their second trimester of healthy singleton pregnancies. Inclusion criteria for this analysis were gestation of ≥34 wk and availability of 25(OH)D and IQ data. Associations between second-trimester 25(OH)D plasma concentration and Stanford-Binet IQ scores in offspring at 4-6 y were examined using multivariable linear regression; interaction terms were used to explore possible effect modification by race., Results: Mean ± SD 25(OH)D concentration among 1019 eligible dyads was 21.6 ± 8.4 ng/mL, measured at a mean ± SD gestational age of 23.0 ± 3.0 wk. Vitamin D deficiency [25(OH)D < 20 ng/mL] was observed in 45.6%. Maternal 25(OH)D differed by race with a mean ± SD of 19.8 ± 7.2 ng/mL in Blacks sand 25.9 ± 9.3 ng/mL in Whites ( P  < 0.001). In adjusted models a 10-ng/mL increase in 25(OH)D was associated with a 1.17-point higher Full Scale IQ (95% CI: 0.27, 2.06 points), a 1.17-point higher Verbal IQ (95% CI: 0.19, 2.15 points), and a 1.03-point higher Nonverbal IQ (95% CI: 0.10, 1.95 points). We observed no evidence of effect modification by race., Conclusions: Second-trimester maternal 25(OH)D was positively associated with IQ at 4-6 y, suggesting that gestational vitamin D status may be an important predictor of neurocognitive development. These findings may help inform prenatal nutrition recommendations and may be especially relevant for Black and other dark-skinned women at high risk of vitamin D deficiency., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: A taxonomy of ninety-three functionally different behaviour change techniques (BCTs) has been identified. However, it is not fully clear how these and other theory-based techniques are applied in the day-to-day practice of people delivering health behaviour change interventions. This study examines feedback provided by expert health coaches in a behavioural weight-loss intervention, to describe; a) what theory-based techniques are used in sessions, b) which techniques are used most frequently, c) what occurs in sessions, beyond existing theory-based techniques. Main Outcome Measures: Theory-based techniques (BCTs/tailoring strategies); relational/content-based techniques. Design: 10 tailored feedback videos from two health coaches were coded using a hybrid thematic analysis approach. Theory-based techniques were coded deductively; content not matching definitions of theory-based techniques but that addressed a determinant of behaviour change were coded inductively and relational codes were connected into themes. Results: Seventeen BCTs were coded M  = 20.88 times (range:1-109). Eight tailoring techniques were coded M  = 25.25 times (range:1-91). Relational themes included; 'Autonomous interpersonal coaching style,' 'Supportive accountability,' and 'Coach as expert'. Additional behavioural techniques were also identified. Conclusion: This work highlights what and how theory-based techniques are implemented in a weight-loss intervention, drawing attention to the role of tailoring techniques and health coaches in supporting behaviour change.

An earlier study in monkeys indicated that lesions to the mid-portion of the ventral orbitofrontal cortex (OFC), including Walker's areas 11 and 13 (OFC11/13), altered the spontaneous scanning of still pictures of primate faces (neutral and emotional) and the modulation of arousal. Yet, these conclusions were limited by several shortcomings, including the lesion approach, use of static rather than dynamic stimuli, and manual data analyses. To confirm and extend these earlier findings, we compared attention and arousal to social and nonsocial scenes in three groups of rhesus macaques with restricted lesions to one of three OFC areas (OFC12, OFC13, or OFC14) and a sham-operated control group using eye-tracking to capture scanning patterns, focal attention and pupil size. Animals with damage to the lateral OFC areas (OFC12 and OFC13) showed decreased attention specifically to the eyes of negative (threatening) social stimuli and increased arousal (increased pupil diameter) to positive social scenes. In contrast, animals with damage to the ventromedial OFC area (OFC14) displayed no differences in attention or arousal in the presence of social stimuli compared to controls. These findings support the notion that areas of the lateral OFC are critical for directing attention and modulating arousal to emotional social cues. Together with the existence of face-selective neurons in these lateral OFC areas, the data suggest that the lateral OFC may set the stage for multidimensional information processing related to faces and emotion and may be involved in social judgments., (Copyright © 2020 Murphy and Bachevalier.)

Lay Abstract: Autistic adults have more health problems then their same-aged peers. Yet little research has been conducted that focuses on addressing these health problems. In order to guide future research, it is important to know what intervention studies have been done to improve health outcomes among autistic adults. The project team and student assistants read studies that were published between 2007 and 2018 in the online research database, PubMed. We looked for studies published in English, which were peer-reviewed and included (1) an intervention, (2) an outcome that was related to health, and (3) a study group that included autistic adults. We did not include studies that had outcomes about employment (unless there was a health outcome), studies about caregivers or caregiving, or expert opinions about interventions. Of 778 reviewed articles, 19 studies met all of the criteria above. Within these studies, two approaches were found to have emerging evidence for their use in autistic adults: cognitive behavioral interventions and mindfulness-based approaches for improved mental health outcomes. The remaining intervention approaches did not have enough articles to support their use. Many of the outcomes were about reduced symptoms of co-occurring mental health diagnoses (e.g. reduced anxiety, depression). Most of the participants in these studies were male and did not have intellectual disability. Most study participants were adults younger than 40. There are not many intervention studies that address health outcomes among autistic adults. More research is needed on interventions which are desired by the adult autism community and address preferred health outcomes such as increased quality of life or well-being.

Background: Early life stress has enduring effects on physical and mental health. Hair cortisol concentrations (HCCs) reflect exposures to contextual stressors in early life, but are understudied in preschool children., Methods: Hair samples from children (N = 693) during clinic visits (CVs) scheduled at 1-4 years (CV1-CV4) were measured using validated assay methods for HCC., Results: HCCs were highest at CV1 and decreased at CV2-CV4, with no sex differences. Black children had higher HCC than White/other children; these differences persisted even after adjusting for socioeconomic factors. Bivariable analyses showed significant effects on HCC for Black race, with specific demographic and psychosocial factors at different ages. Multivariable analyses showed that higher HCC at CV1 were associated with Black race and male sex; at CV2 with Black race, lower maternal self-esteem, socioeconomic adversity, and the child's risk for developmental delay; at CV3 with Black race; at CV4 with maternal depression and the child's prior HCC values., Conclusions: HCCs were higher in Black children than White/other races; differences were related to maternal factors, socioeconomic adversity, and the child's risk for developmental delay. Public health measures to reduce disparities between Blacks and other races must also consider the long-term effects of chronic stress in early life.

The majority (55%) of the world's population lives in urban environments. Of relevance to global mental health, the rapid growth in urban populations around the world and the attendant risks coincide with the presence of the largest population of adolescents the global community has seen to date. Recent reviews on the effects of the urban environment on mental health report a greater risk of depression, anxiety, and some psychotic disorders among urban dwellers. Increased risk for mental disorders is associated with concentrated poverty, low social capital, social segregation, and other social and environmental adversities that occur more frequently in cities. To address these problems, urban adolescent mental health requires attention from decision makers as well as advocates who seek to establish sustainable cities. We examine opportunities to increase the prominence of urban adolescent mental health on the global health and development agenda using Shiffman and Smith's framework for policy priorities, and we explore approaches to increasing its relevance for urban health and development policy communities. We conclude with suggestions for expanding the community of actors who guide the field and bridging the fields of mental health and urban development to meet urban adolescent mental health needs., (Copyright © 2020 Murphy, Jack, Concepcion and Collins.)

Throughout infancy and early childhood, stable and secure relationships with caregivers are needed to promote optimal socioemotional (SE) and cognitive development.The objective is to examine socio-demographic, maternal, and child indicators of SE problems in 2-year-olds living in an urban-suburban community in the southern United States.Mother-infant pairs enrolled in a prospective pregnancy cohort study.Shelby County (Memphis), Tennessee.One thousand five hundred three women were recruited during their second trimester and followed with their children through the child's age of 2 years.Child SE development was measured by the Brief Infant-Toddler Social Emotional Assessment at 2 years of age. Mothers reported their own behavioral and mental health, temperament, parenting stress, and potential for child abuse during gestation and/or when their child was 1 year of age. Examiners measured maternal IQ during data collection at the child's age of 1 year. Child communication, cognitive development, and risk for autism spectrum disorder were assessed at 1 and 2 years of age. Multivariable regression models were developed to predict mother-reported SE problems.In bivariate analyses, multiple maternal behavioral and mental health indicators and child cognitive skills were associated with reported child SE problems at 2 years of age. Regression analyses, controlling for socio-demographic, maternal, and child variables, showed the following factors were independently associated with mother-reported child SE problems: maternal education of high school or less, lower maternal IQ, higher maternal cyclothymic temperament score, greater parenting stress, greater maternal psychological distress, lower child expressive communication score, and child risk for autism spectrum disorder. Socio-demographic variables accounted for the variance often attributed to race.Since mothers in the study were medically low-risk, generalizing these findings to medically high-risk mothers is unwarranted. In addition, these SE outcomes in 2-year-old children do not reflect the trajectory of SE development throughout early childhood.Attention to independent indicators of future SE problems in children may help identify individual children and families needing intervention and target public prevention/treatment programs in communities.

Background: Sleep problems have been associated with autism spectrum disorder (ASD) symptoms and diagnosis. However, past research has studied the simultaneous association of sleep problems with precursor ASD symptoms. Using data from a birth cohort, we estimate prospective associations between infant sleep characteristics at 12 months and later ASD screening scores at 24 months., Methods: We obtained data from children (N = 1,096) and their mothers as participants in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood longitudinal birth cohort study. Mothers were enrolled between 2006 and 2011, when they were 16-26 weeks pregnant. Using linear regression, we examined the influence of infant sleep characteristics (nighttime and daytime sleep, night wakings, and sleep onset latency) at 12 months on ASD screening scores at 24 months while controlling for other psychosocial characteristics., Results: The number of night wakings was the only sleep characteristic at 12 months to be significantly associated with the development of early ASD symptoms at 24 months (B = 0.097, P = .021; 95% CI, 0.014 to 0.180). However, other competing risks, especially child socioemotional competence at 12 months (B = 0.573, P < .001; 95% CI, 0.361 to 0.785), showed stronger relative contributions in predicting ASD risk., Conclusions: Infants with more sleep problems by 12 months, especially those waking more often during the night, showed an increased number of early ASD symptoms a year later. This study suggests that infant sleep characteristics could constitute one clinical sign of ASD risk, together with key psychosocial characteristics., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Background: Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Intellectual Disability (ID) are common co-occurring neurodevelopmental disorders; however, limited research exists regarding the presentation and severity of overlapping symptomology, particularly inattention and hyperactivity/impulsivity, when a child is diagnosed with one of more of these neurodevelopmental disorders., Aims: As difficulties with inattention and hyperactivity/impulsivity are symptoms frequently associated with these disorders, the current study aims to determine the differences in the severity of inattention and hyperactivity/impulsivity in children diagnosed with ADHD, ASD, ID, and co-occurring diagnosis of ADHD/ID, ASD/ADHD, and ASD/ID., Methods and Procedures: Participants in the current study included 113 children between the ages of 6 and 11 who were diagnosed with ADHD, ASD, ID, ADHD/ID, ASD/ADHD, or ASD/ID. Two MANOVA analyses were used to compare these groups witih respsect to symptom (i.e., inattention, hyperactivity/impulsivity) severity., Outcomes and Results: Results indicated that the majority of diagnostic groups experienced elevated levels of both inattention and hyperactivity/impulsivity. However, results yielded differences in inattention and hyperactivity/impulsivity severity. In addition, differences in measure sensitivity across behavioral instruments was found., Conclusions and Implications: Children with neurodevelopmental disorders often exhibit inattention and hyperactivity/impulsivity, particularly those with ADHD, ASD, ASD/ADHD, and ADHD/ID; therefore, differential diagnosis may be complicated due to similarities in ADHD symptom severity. However, intellectual abilities may be an important consideration for practitioners in the differential diagnosis process as children with ID and ASD/ID exhibited significantly less inattention and hyperactive/impulsive behaviors. Additionally, the use of multiple behavior rating measures in conjunction with other assessment procedures may help practitioners determine the most appropriate diagnosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Unprotected intercourse after oral emergency contraception (EC) significantly increases pregnancy risk. This underlies the importance of promptly starting effective, ongoing contraception - known as 'quick starting'. However, theoretical concern exists that quick starting might interact with EC or hormonal contraception (HC) potentially causing adverse side effects., Method: A systematic review was conducted, evaluating quick starting HC after oral EC [levonorgestrel 1.5 mg (LNG) or ulipristal acetate 30 mg (UPA)]. PubMed, EMBASE, The Cochrane Library, ICTRP, ClinicalTrials.gov and relevant reference lists were searched in February 2016. A lack of comparable studies prevented meta-analysis., Results: Three randomised controlled trials were identified. Two biomedical studies suggested HC action was unaffected by quick starting after UPA; one study examined ovarian quiescence (OR 1.27; 95% CI 0.51-3.18) while taking combined oral contraception (COC). Another assessed cervical mucus impenetrability (OR 0.76; 95% CI 0.27-2.13) while taking progestogen-only pills (POP). Quick starting POP reduced the ability of UPA to delay ovulation (OR 0.04; 95% CI 0.01-0.37). Side effects (OR 1.22; 95% CI 0.48-3.12) and unscheduled bleeding (OR 0.53; 95% CI 0.16-1.81) were unaffected by quick starting COC after UPA. Another study reported higher self-reported contraceptive use at 8 weeks among women quick starting POP after LNG, compared with women given LNG alone (OR 6.73; 95% CI 2.14-21.20)., Competing Interests: Competing interests: None declared., (© Faculty of Sexual and Reproductive Healthcare of the Royal College of Obstetricians and Gynaecologists (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Mothers' interactions with their young children have predicted later child development, behavior, and health, but evidence has been developed mainly in at-risk clinical samples. An economically and racially diverse sample of pregnant women who were not experiencing a high-risk pregnancy were recruited to participate in a community-based, longitudinal study of factors associated with child cognitive and social-emotional development during the first 3 years. The purpose of the present analysis was to identify associations between the characteristics of 1125 mothers and their 1-year-olds and the mothers' and children's scores on the Nursing Child Assessment Teaching Scale (NCATS). A multivariable approach was used to identify maternal and child characteristics associated with NCATS scores and to develop prediction models for NCATS total and subscale scores of mothers and children. Child expressive and receptive communication and maternal IQ, marital status, age, and insurance predicted NCATS Mother total score, accounting for 28% of the score variance. Child expressive communication and birth weight predicted the NCATS Child total score, accounting for 4% of variance. Child's expressive communication and mother's IQ and marital status predicted NCATS mother-child total scores. While these findings were similar to reports of NCATS scores in at-risk populations, no previous teams examined all of the mother and child characteristics included in this analysis. These findings support the utility of the NCATS for assessing mother-child interaction and predicting child outcomes in community-based, non-clinical populations. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Introduction: Collagenase Clostridium Histolyticum (CCH) is a recognised treatment option for adult patients presenting with Dupuytren's contracture (DC)., Patients and Methods: Twenty male patients with established DC were treated using CCH. The average metacarpophalangeal (MCP) joint and proximal interphalangeal joint (PIP) contractures pre-treatment were 52 0 (range, 0 - 75 0 ) and 35 0 (range, 0 - 84 0 ) respectively. The average DASH score pre-treatment was 24.2 points (range, 0 - 68.2 points). Patients were reviewed at lmonth, 3months and at an average of 23 months (17 to 27 months)., Results: MCP joint contractures significantly improved compared to pre-treatment and the improvement was maintained at latest follow up. PIP joint contractures did significantly improve but to a lesser degree and there was no significant improvement compared to pre-treatment beyond 3months. A trend for MCP and PIP joint contracture recurrence was observed at latest follow up but did not reach statistical significance. DASH scores significantly improved from pre-treatment and the improvement was maintained at latest follow up. At 3months, the average patient satisfaction score was 9.5 (range, 6 - 10), which decreased to 8.6 (range, 6 - 10) at latest follow up. We estimated a potential cost saving of approximately £70,000 by treating 20 patients using CCH compared to inpatient operative fasciectomy., Conclusion: CCH is a useful option in the management of DC in appropriately selected patients. Cost-effectiveness in the treatment of DC should be carefully considered., Competing Interests: Provenance: externally peer-reviewed.

Introduction: Spinal metastases secondary to renal cell carcinoma are associated with significant intra-operative blood loss. Our aim was to assess if embolisation reduced the intra-operative blood loss and transfusion requirement., Methods: We performed a retrospective cohort study of 25 patients undergoing surgery between 2003 and 2011., Results: 14 underwent pre-operative embolisation; 11 did not. There was no significant difference in intra-operative blood loss, 1336 ml vs 1492 ml in the non-embolised ( p value = 0.116). 43% of embolised patients required an intra operative blood transfusion vs 27% in the non-embolised., Conclusion: Our results suggest that not all patients with spinal metastatic renal carcinoma require pre-operative embolisation.

Emerging data suggest that vitamin D status during childhood and adolescence can affect neurocognitive development. The purpose of this study was to investigate whether gestational 25(OH)D status is associated with early childhood cognitive and receptive language development. The Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) study enrolled 1503 mother-child dyads during the second trimester of healthy singleton pregnancies from Shelby County TN. Among 1020 participants of the total CANDLE cohort for whom 25(OH)D levels were available, mean gestational 25(OH)D level during the second trimester was 22.3 ng/mL (range 5.9-68.4), with 41.7% of values <20 ng/dL. Cognitive and language scaled scores increased in a stair-step manner as gestational 25(OH)D levels in the second trimester rose from <20 ng/dL, through 20-29.99 ng/dL, to ≥30 ng/dL. When controlling for socioeconomic status, race, use of tobacco products, gestational age of the child at birth, and age at the 2-year assessment, the gestational 25(OH)D was positively related to receptive language development (p < 0.017), but not cognitive or expressive language.

Introduction: Current hip fractures guidelines recommend surgery within 36 h of admission. The 2011 National Hip Fracture Database (NHFD) report shows our institute has the fewest patients meeting this target (9%). Northern Irelands' exclusion from the "Best Practice Tariff" means no incentive-led treatment or prioritisation of hip fracture patients., Method: We performed a systematic review of post-operative results to highlight deficiencies in delivery of patient care. We reviewed 702 patients admitted between September 2009 and April 2012. Patients were prospectively identified and added to our Fracture Outcome and Research Database (FORD). Results were compared to national average values from the NHFD., Results: 16.7% of patients met the 36-h target to theatre compared to the UK average of 66%. 81.7% underwent a pre-operative orthogeriatric review. The main reasons for surgical delay were inadequate theatre space (58%) and medically unfit patients (29%). After exclusion of medically unfit patients, medically fit patients were divided into delayed surgery and not delayed categories. Medically fit patients who had delayed surgery had inferior outcomes- longer hospital stay and higher mortality as an inpatient and at 30 days., Conclusion: Without a change in funding, Northern Ireland will struggle to compete with the UK mainland and decrease mortality in this patient group., (Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Multiple studies show that molecular genetic changes and epigenetic modifications affect the risk of cognitive disability or impairment. However, the role of epigenetic variation in cognitive development of neurotypical young children remains largely unknown. Using data from a prospective, community-based study of mother-infant pairs, we investigated the association of DNA methylation patterns in neonatal umbilical cord blood with cognitive and language development at 1 year of age. No CpG loci achieved genome-wide significance, although a small number of weakly suggestive associations with Bayley-III Receptive Communication scales were noted. While umbilical cord blood is a convenient resource for genetic analyses of birth outcomes, our results do not provide conclusive evidence that its use for DNA methylation profiling yields epigenetic markers that are directly related to postnatal neurocognitive outcomes at 1 year of age.

Objective: To determine demographic, maternal, and child factors associated with socioemotional (SE) problems and chronic stress in 1-year-old children., Study Design: This was a prospective, longitudinal, community-based study, which followed mother-infant dyads (n = 1070; representative of race, education, and income status of Memphis/Shelby County, Tennessee) from midgestation into early childhood. Child SE development was measured using the Brief Infant-Toddler Social and Emotional Assessment in all 1097 1-year-olds. Chronic stress was assessed by hair cortisol in a subsample of 1-year-olds (n = 297). Multivariate regression models were developed to predict SE problems and hair cortisol levels., Results: More black mothers than white mothers reported SE problems in their 1-year-olds (32.9% vs 10.2%; P < .001). In multivariate regression, SE problems in blacks were predicted by lower maternal education, greater parenting stress and maternal psychological distress, and higher cyclothymic personality score. In whites, predictors of SE problems were Medicaid insurance, higher maternal depression score at 1 year, greater parenting stress and maternal psychological distress, higher dysthymic personality score, and male sex. SE problem scores were associated with higher hair cortisol levels (P = .01). Blacks had higher hair cortisol levels than whites (P < .001). In the entire subsample, increased hair cortisol levels were associated with higher parenting stress (P = .001), lower maternal depression score (P = .01), lower birth length (P < .001), and greater length at 1 year of age (P = .003)., Conclusion: Differences in maternal education, insurance, mental health, and early stress may disrupt SE development in children. Complex relationships between hair cortisol level in 1-year-olds and maternal parenting stress and depression symptoms suggest dysregulation of the child's hypothalamic-pituitary-adrenal axis., (Copyright © 2013 Mosby, Inc. All rights reserved.)

The human faculty for object-mediated action, including tool use and imitation, exceeds that of even our closest primate relatives and is a key foundation of human cognitive and cultural uniqueness. In humans and macaques, observing object-directed grasping actions activates a network of frontal, parietal, and occipitotemporal brain regions, but differences in human and macaque activation suggest that this system has been a focus of selection in the primate lineage. To study the evolution of this system, we performed functional neuroimaging in humans' closest living relatives, chimpanzees. We compare activations during performance of an object-directed manual grasping action, observation of the same action, and observation of a mimed version of the action that consisted of only movements without results. Performance and observation of the same action activated a distributed frontoparietal network similar to that reported in macaques and humans. Like humans and unlike macaques, these regions were also activated by observing movements without results. However, in a direct chimpanzee/human comparison, we also identified unique aspects of human neural responses to observed grasping. Chimpanzee activation showed a prefrontal bias, including significantly more activity in ventrolateral prefrontal cortex, whereas human activation was more evenly distributed across more posterior regions, including significantly more activation in ventral premotor cortex, inferior parietal cortex, and inferotemporal cortex. This indicates a more "bottom-up" representation of observed action in the human brain and suggests that the evolution of tool use, social learning, and cumulative culture may have involved modifications of frontoparietal interactions.

Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been associated with idiopathic male infertility, few studies have examined other folate-related metabolites and genes. We investigated whether idiopathic male infertility is associated with variants in folate, vitamin B(12) (B12) and total homocysteine (tHcy)-related genes and measured these metabolites in blood. We conducted a case-control study that included 153 men with idiopathic infertility and 184 fertile male controls recruited at the Fertility Center and Antenatal Care Center, University Hospital, Malmö and Lund, Sweden. Serum folate, red cell folate (RCF), serum B12, plasma tHcy and semen quality were measured. Subjects were genotyped for 20 common variants in 12 genes related to folate/B12/homocysteine metabolism. Metabolite concentrations and genotype distributions were compared between cases and controls using linear and logistic regression with adjustment for covariates. The phosphatidylethanolamine N-methyltransferase (PEMT) M175V and TCblR rs173665 polymorphisms were significantly associated with infertility (P=0.01 and P=0.009, respectively), but not with semen quality. Among non-users of supplements, infertile men had lower serum folate concentrations than fertile men (12.89 vs. 14.73 nmol l(-1); P=0.02), but there were no significant differences in RCF, B12 or tHcy. Folate, B12 and tHcy concentrations were not correlated with any semen parameters. This study provides little support for low folate or B12 status in the pathogenesis of idiopathic male infertility. Although additional data are needed to confirm these initial findings, our results suggest that PEMT and TCblR, genes involved in choline and B12 metabolism, merit further investigation in idiopathic male infertility.

Fifty-five women were recruited and assigned to a control group or an oral contraceptive (OC) use group. For the control groups menstrual cycle phase was determined using a menstrual calendar and only participants with regular cycles were recruited. Testing was carried out during a single day of the luteal and follicular phases, where participants were asked to consume and rate sweet and savoury snacks. Participants in the OC group were tested on the equivalent days of their pill calendar. In both groups, the luteal phase induced a greater caloric intake of sweet foods without altering hedonic ratings. No significant interactions between either phase or flavour with OC use on food intake or hedonic food ratings were found. At least for snack items, OC do not seem to alter the caloric intake fluctuations that occur during a normal menstrual cycle., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Prenatal and postnatal polychlorinated biphenyl (PCBs) exposure has been associated with decrements in fetal and infant growth and development, although exposures during the preconception window have not been examined despite recent evidence suggesting that this window may correspond with the highest serum concentrations., Objectives: We assessed maternal serum PCB concentrations at two sensitive developmental windows in relation to birth weight., Methods: Serum samples were collected from 99 women as they began trying to become pregnant (preconception) and after a positive pregnancy test (prenatal); 52 (53%) women gave birth and represent the study cohort. Using daily diaries, women recorded sexual intercourse, menstruation, and home pregnancy test results until pregnant or up to 12 menstrual cycles with intercourse during the estimated fertile window. With gas chromatography with electron capture, 76 PCB congeners were quantified (nanograms per gram serum) and subsequently categorized by purported biologic activity. Serum PCBs were log-transformed and entered both as continuous and categorized exposures along with birth weight (grams) and covariates [smoking (yes/no), height (inches), and infant sex (male/female)] into linear regression., Results: A substantial reduction in birth weight (grams) was observed for women in the highest versus the lowest tertile of preconception antiestrogenic PCB concentration (beta; = 429.3 g, p = 0.038) even after adjusting for covariates (beta; = 470.8, p = 0.04)., Conclusions: These data reflect the potential developmental toxicity of antiestrogenic PCBs, particularly during the sensitive preconception critical window among women with environmentally relevant chemical exposures, and underscore the importance of PCB congener-specific investigation.

Background and Objective: Food intake and motivation for food varies according to the phase of the menstrual cycle. These changes seem to be more marked in women with premenstrual syndrome (PMS) and may be modified by the use of oral contraceptives (OC). This study examined the effect of menstrual cycle, PMS and OC use on the intake and hedonic rating of sweet and savory snack foods., Material and Methods: Fifty-five women were recruited and assigned to either a PMS group or a control group. In addition, based on OC use, the women were assigned to an OC-user or non-user group. During the luteal and follicular phases, the participants were asked to consume and rate sweet and savory snacks., Results: The luteal phase induced greater caloric intake from sweet foods. PMS sufferers did not consume significantly more calories in either phase. There was a significant interaction between phase, flavor, PMS status and OC use. OC users consumed more calories from sweet foods in the follicular phase., Conclusions: Food intake is increased in the luteal phase. This effect was modulated by both PMS and OC use. OC use seems to eliminate cyclic fluctuations in caloric intake.

Background and Purpose: Nicotinamide (NA) is currently undergoing clinical trials as a tumour radiosensitizer. The dose that can be administered is currently 80 mg/kg per day, but this may be restricted to 60 mg/kg per day by the high incidence of nausea and vomiting. To investigate some of NA's underlying mechanisms of action, we have used an ex vivo system to study the direct effect of this drug, over a wide range of concentrations, on isolated spontaneously active rat ileum. Effects on the gut were compared with the action of NA on skeletal and vascular smooth muscle., Materials and Methods: Isolated rat ileum rings were perfused with oxygenated Krebs' solution in an organ bath. NA (1 microM to 10 mM) was introduced to the perfusate and the change in amplitude of spontaneous peristaltic activity recorded. Dissected frog sartorius muscle was bathed in modified oxygenated Ringer's solution in an organ bath. The muscle was electrically stimulated to generate isometric contractions. Tension was then measured before and after the addition of a range of NA concentrations (8.2-24.6 mM) to the organ bath., Results: NA inhibited peristalsis in the ileum in a dose-dependent manner. At a drug concentration of 1 mM the amplitude of contractions was reduced to <50% of the initial control value. NA had no effect on the electrically induced contractions in the isolated frog sartorius muscle., Conclusions: Gut smooth muscle is highly sensitive to the relaxant effect of NA producing 50% relaxation at a concentration approximately 10 fold lower than that required in rat arterial smooth muscle, while having no effect on non-mammalian skeletal smooth muscle. This may provide explanations for the occurrence of emesis in patients undergoing combined nicotinamide therapies and highlight possible alternatives available to counter this unwanted side-effect.

The saxitoxin-binding component (SBC) of the excitable membrane sodium channel has been solubilized and purified from rat skeletal muscle sarcolemma. Phospholipid was required in mixed micelles with detergent for stability of the mammalian SBC. Even at optimal detergent-to-phospholipid ratio, the solubilized SBC showed significant temperature-dependent loss of specific toxin binding with time, necessitating maintenance of low temperatures during purification. Characteristics of saxitoxin binding to the solubilized material closely resembled those seen in intact membranes. A weak anion-exchange column was synthesized; it provided rapid 10- to 20-fold purification of the solubilized SBC. Additional necessary purification was obtained by chromatography on immobilized wheat germ agglutinin. Specific saxitoxin-binding activity of the purified material averaged approximately 1500 pmol of saxitoxin bound per mg of protein. Three bands were present in this material on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The purified material sedimented on a sucrose gradient with an apparent s20,w of 9.9 S.

Considerable disagreement exists between results reported by various authors for lipid composition and enzyme activity in purified muscle membrane fractions presumed to be sarcolemma, although an explanation for these discrepancies has not been presented. We have prepared muscle light surface membrane fractions of comparable density (1.050--1.120) by a low-salt sucrose method and by an LiBr-KCl extraction procedure and compared them for density profile, total lipid and cholesterol content, protein composition and ATPase activity. In addition, sodium channels characteristic of excitable membranes have been quantitated in each preparation using [3H]saxitoxin binding assays, and the density of acetylcholine receptors determined in fractions from control and denervated muscle using alpha-[125I]bungarotoxin. Although both fractions contain predominantly surface membrane, the LiBr fraction consistently shows the higher specific activity of p-nitrophenylphosphatase, higher free cholesterol content, and higher density of sodium channels and acetylcholine receptors. The density distribution of sodium channels appears uniform throughout both fractions. Quantitative differences were seen between sodium dodecyl sulfate polyacrylamide gel electrophoresis patterns of membrane proteins from the two preparations although most bands are represented in both. A majority of the low-salt sucrose light membrane proteins were accessible in varying degrees to labelling with diazotized diiodosulfanylic acid in intact muscle. These results suggest that light surface membrane fractions may be mixtures of sarcolemma and T-tubular membranes. Using our preparative methods, the LiBr fraction may contain predominantly sarcolemma while low-salt sucrose light membranes may be enriched in T-tubular elements.

The sodium channel saxitoxin binding component from rat sarcolemma was solubilized with medium chain length non-ionic detergents including NP-40, Brij-96 and Lubrol-PX. Phospholipid was required for stability of the binding component. Specific saxitoxin binding was significantly temperature sensitive even with optimal levels of phospholipid present. The solubilized saxitoxin binding component chromatographed on Sepharose 6B at a position corresponding to that of a globular protein of 95--10 A Stokes radius, but had an apparent s20,w typical of a smaller molecule (s20,w = 9.2--10). Column behavior and s20,w were independent of the specific detergent used for solubilization. Anomalous column behavior may reflect molecular asymmetry, contribution from bound detergent or similar considerations.

The sodium channel saxitoxin binding component from rat sarcolemma was solubilized with NP-40 and centrifuged on sucrose gradients constructed in either D2O or H2O. When compared with a series of standard proteins the sedimentation behavior of the solubilized channel complex changed from an apparent S20,w of 9.1 in H2O to 6.1 in D2O. From these observations, a true partial specific volume of 0.83 ml/g was calculated for the complex. A Stokes radius of 8.6 nm was estimated from Sepharose 6-B chromatography in NP-40. The calculated protein molecular weight of the lipid-protein-detergent complex based on these data is 560,000. The complex contains about 56% protein, and the calculated molecular weight of this component is 314,000 if a v for the protein of 0.74 ml/g is assumed.