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Racial inequities in blood pressure levels have been extensively documented. Experiences of racial discrimination could explain some of this disparity, although findings from previous studies have been inconsistent. To address limitations of prior literature, including measurement error, we implemented instrumental variable analysis to assess the relationship between racial discrimination in institutional settings and blood pressure. Using data from 3,876 Black and White adults with an average age of 32 years from examination 4 (1992-1993) of the Coronary Artery Risk Development in Young Adults Study, our primary analysis examined the relationship between self-reported experiences of racial discrimination in institutional settings and blood pressure using reflectance meter measurement of skin color as an instrument. Findings suggested that an increase in experiences of racial discrimination was associated with higher systolic and diastolic blood pressure (β = 2.23 mm Hg (95% confidence interval: 1.85, 2.61) and β = 1.31 (95% confidence interval: 1.00, 1.62), respectively). Our instrumental variable estimates suggest that experiences of racial discrimination within institutional settings contribute to racial inequities in elevated blood pressure and cardiovascular disease outcomes in a relatively young cohort of adults and may yield clinically relevant differences in cardiovascular health over the life course., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Artemis nuclease and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are key components in nonhomologous DNA end joining (NHEJ), the major repair mechanism for double-strand DNA breaks. Artemis activation by DNA-PKcs resolves hairpin DNA ends formed during V(D)J recombination. Artemis deficiency disrupts development of adaptive immunity and leads to radiosensitive T- B- severe combined immunodeficiency (RS-SCID). An activated state of Artemis in complex with DNA-PK was solved by cryo-EM recently, which showed Artemis bound to the DNA. Here, we report that the pre-activated form (basal state) of the Artemis:DNA-PKcs complex is stable on an agarose-acrylamide gel system, and suitable for cryo-EM structural analysis. Structures show that the Artemis catalytic domain is dynamically positioned externally to DNA-PKcs prior to ABCDE autophosphorylation and show how both the catalytic and regulatory domains of Artemis interact with the N-HEAT and FAT domains of DNA-PKcs. We define a mutually exclusive binding site for Artemis and XRCC4 on DNA-PKcs and show that an XRCC4 peptide disrupts the Artemis:DNA-PKcs complex. All of the findings are useful in explaining how a hypomorphic L3062R missense mutation of DNA-PKcs could lead to insufficient Artemis activation, hence RS-SCID. Our results provide various target site candidates to design disruptors for Artemis:DNA-PKcs complex formation., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Methods for calculating health indicators profoundly influence understanding of and action on population health and inequities. Age-standardization can be useful and is commonly applied to account for differences in age structures when comparing health indicators across groups. Age-standardized rates have well-acknowledged limitations, including that they are relative indices for comparison, and not accurate measures of actual rates where the age structures of groups diverge. This paper explores these limitations, and demonstrates alternative approaches through a case study quantifying mortality rates within the Aboriginal and Torres Strait Islander (Indigenous) population of Australia and inequities compared with the non-Indigenous population, over 2001-16. Applying the Australian Standard Population, the Aboriginal and Torres Strait Islander age-standardized mortality rate was more than double the crude mortality rate in 2001 and 2016, inflated through high weighting of older age groups. Despite divergent population age structures, age-standardized mortality rates remain a key policy metric for measuring progress in reducing Indigenous-non-Indigenous inequities in Australia. Focusing on outcomes age-standardized to the total population can obscure inequities, and denies Aboriginal and Torres Strait Islander peoples and communities valid, actionable information about their health and well-being. Age-specific statistics convey the true magnitude of health risks and highlight high-risk subgroups. When requiring standardization, standardizing to a population-specific standard (here, an Indigenous standard) generates metrics centred around and reflective of reality for the population of focus, supporting communities' self-determination to identify priorities and informing resource allocation and service delivery. The principles outlined here apply across populations, including Indigenous and other populations internationally., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Study Objectives: African-Americans have a high burden of poor sleep, yet, psychosocial determinants (e.g. discrimination) are understudied. We investigated longitudinal associations between everyday discrimination and sleep quality and duration among African-Americans (N = 3404) in the Jackson Heart Study., Methods: At Exam 1 (2000-2004) and Exam 3 (2008-2013), participants completed the Everyday Discrimination Scale, rated their sleep quality (1 = poor to 5 = excellent), and self-reported hours of sleep. A subset of participants (N = 762) underwent 7-day actigraphy to objectively measure sleep duration and sleep quality (Sleep Exam 2012-2016). Changes in discrimination were defined as low stable (reference), increasing, decreasing, and high stable. Within-person changes in sleep from Exam 1 to Exam 3 were regressed on change in discrimination from Exam 1 to Exam 3 while adjusting for age, sex, education, income, employment, physical activity, smoking, body mass index, social support, and stress., Results: At Exam 1, the mean age was 54.1 (12.0) years; 64% were female, mean sleep quality was 3.0 (1.1) and 54% were short sleepers. The distribution of the discrimination change trajectories were 54.1% low stable, 13.5% increasing, 14.6% decreasing, and 17.7% were high stable. Participants who were in the increasing (vs. low stable) discrimination group had greater decrease in sleep quality. There was no association between change in discrimination and change in sleep duration. Among Sleep Exam participants, higher discrimination was cross-sectionally associated with shorter self-reported sleep duration, independent of stress., Conclusion: Discrimination is a unique stressor for African-Americans; thus, future research should identify interventions to reduce the burden of discrimination on sleep quality., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Racial/ethnic discrimination may contribute to the risk of type 2 diabetes mellitus (T2DM), but few studies have prospectively examined this relationship among racially/ethnically diverse populations. We analyzed prospective data from 33,833 eligible Sister Study participants enrolled from 2003 to 2009. In a follow-up questionnaire (2008-2012), participants reported their lifetime experiences of everyday and major forms of racial/ethnic discrimination. Self-reported physician diagnoses of T2DM were ascertained through September 2017. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models, overall and by race/ethnicity. Mean age at enrollment was 54.9 (standard deviation, 8.8) years; 90% of participants self-identified as non-Hispanic (NH) White, 7% as NH Black, and 3% as Hispanic/Latina. Over an average of 7 years of follow-up, there were 1,167 incident cases of T2DM. NH Black women most frequently reported everyday (75%) and major (51%) racial/ethnic discrimination (vs. 4% and 2% of NH White women, respectively, and 32% and 16% of Hispanic/Latina women, respectively). While everyday discrimination was not associated with T2DM risk, experiencing major discrimination was marginally associated with higher T2DM risk overall (hazard ratio = 1.26, 95% confidence interval: 0.99, 1.61) after adjustment for sociodemographic characteristics and body mass index. Associations were similar across racial/ethnic groups; however, racial/ethnic discrimination was more frequently reported among racial/ethnic minority women. Antidiscrimination efforts may help mitigate racial/ethnic disparities in T2DM risk., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

We assessed whether race moderates the association between flourishing and all-cause mortality. We used panel data from the Midlife in the United States Study (MIDUS) (1995-2016; n = 2,851). Approximately 19% of White respondents and 23% of Black respondents in the baseline sample died over the course of the 21-year study period (n = 564). Cox proportional hazard models showed that Blacks had a higher mortality rate relative to Whites and higher levels of flourishing were associated with a lower mortality rate. Furthermore, a significant interaction between flourishing and race in predicting death was observed. Blacks with higher levels of flourishing had a mortality rate that was not significantly different from that of Whites. However, Blacks, but not Whites, with low flourishing scores had a higher mortality rate. As such, health-promotion efforts focused on enhancing flourishing among Black populations may reduce the Black-White gap in mortalityrate., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Perceived discrimination is a risk factor for poor mental health. However, most studies measure discrimination at one time point, which does not account for heterogeneity in the cumulative patterning of exposure to discrimination. To address this gap, we examine the association between discrimination trajectories and depressive symptoms among black middle-aged and older adults., Research Design and Methods: Data were analyzed from a subsample of black Health and Retirement Study respondents (2006-2018, N = 2926, older than 50 years). General discrimination and racial discrimination trajectories were constructed based on the Everyday Discrimination Scale using repeated measures latent profile analyses. We examined the extent to which the association between discrimination trajectories are differentially associated with depressive symptoms (8-item Center for Epidemiological Studies-Depression scale) using negative binomial regression models adjusted for potential confounders. Effect modification by age and gender was tested., Results: Individuals in the persistently high (incident rate ratio [IRR]: 1.70; 95% confidence interval [CI]: 1.49-1.95) and moderate general discrimination trajectories (IRR: 1.19; 95% CI: 1.06-1.33) were more likely to have elevated depressive symptoms in comparison to those in the persistently low trajectory. This relationship was strongest among older adults aged older than 65 years. Respondents in the persistently high racial discrimination trajectory (IRR: 1.50; 95% CI: 1.29-1.73) had a higher risk of elevated depressive symptoms in comparison to respondents in the persistently low trajectory. Sensitivity analyses indicated that there was an independent association between persistently high racial discrimination trajectory class and elevated depressive symptoms, after adjusting for racial discrimination measured at a single time point., Discussion and Implications: Characterizing longitudinal patterns of perceived discrimination may facilitate the stratification of mental health risk and vulnerability among black middle-aged and older adults. Trajectories of racial discrimination may inform risk of worse depressive symptoms more accurately than a single assessment of discrimination., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: The Centers for Disease Control and Prevention (CDC) offer behavioral guidance to prevent the spread of infectious diseases like COVID-19. Cleaning (e.g., cleaning surfaces, washing and sanitizing hands) and containing (e.g., covering coughs, keeping distance from others, especially sick people) behaviors are recommended., Purpose: To develop the Clean and Contain Measure, a brief measure of compliance with CDC recommendations for prevention of infectious disease, and validate the measure in individuals experiencing the COVID-19 pandemic., Methods: Participants were recruited from Amazon Mechanical Turk and social media., Results: In Study 1 (N = 97), exploratory factor analysis revealed two scales: (a) five items assessing cleaning behaviors and (b) four items assessing containing behaviors. Simple structure was obtained and alpha coefficients for both scales were >.83. In Studies 2 (N = 204) and 3 (N = 527), confirmatory factor analysis verified the identical factor structure found in Study 1. All loadings were statistically significant at p < .001. Alpha coefficients for both scales were >.84 for Studies 2 and 3., Conclusions: Our measure is a reliable and valid indicator of compliance with cleaning and containing health behaviors that help to prevent the spread of diseases like COVID-19. Future research should replicate construct validity in more diverse samples and continue to refine items, examine construct validity, including predictive and discriminant validity, and improve the measure for future use. With continued use and refinement, this measure could allow health officials and researchers to accurately assess compliance with important infection prevention behavior guidelines., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Short sleep duration is associated with increased cardiovascular disease (CVD) risk. However, it is uncertain whether sleep debt, a measure of sleep deficiency during the week compared to the weekend, confers increased cardiovascular risk. Because sleep disturbances increase with age particularly in women, we examined the relationship between sleep debt and ideal cardiovascular health (ICH) in older women., Methods: Sleep debt is defined as the difference between self-reported total weekday and weekend sleep hours of at least 2 hours among women without apparent CVD and cancer participating in the Women's Health Stress Study follow-up cohort of female health professionals (N = 22 082). The ICH consisted of seven health factors and behaviors as defined by the American Heart Association Strategic 2020 goals including body mass index, smoking, physical activity, diet, blood pressure, total cholesterol, and glucose., Results: Mean age was 72.1 ± 6.0 years. Compared to women with no sleep debt, women with sleep debt were more likely to be obese and have hypertension (pall < .05). Linear regression models adjusted for age and race/ethnicity revealed that sleep debt was significantly associated with poorer ICH (B = -0.13 [95% CI = -0.18 to -0.08]). The relationship was attenuated but remained significant after adjustment for education, income, depression/anxiety, cumulative stress, and snoring., Conclusion: Sleep debt was associated with poorer ICH, despite taking into account socioeconomic status and psychosocial factors. These results suggest that weekly sleep duration variation, possibly leading to circadian misalignment, may be associated with cardiovascular risk in older women., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Psychosocial stress has been implicated as a risk factor for overweight and obesity. However, research on psychosocial stressors and overweight and obesity has typically focused on single stressors in isolation, which may overestimate the impact of a specific stressor and fail to describe the role of cumulative stress on overweight and obesity risk., Purpose: This study explores the association between overweight/obesity and cumulative exposure to a wide range of psychosocial stressors, among a multiracial/ethnic sample of adults., Methods: Using secondary data from the Chicago Community Adult Health Study (n = 2,983), we conducted multinomial logistic regression analyses to quantify associations between eight psychosocial stressors, individually and in combination, and measured overweight and obesity, adjusted for sociodemographic factors, alcohol use and smoking., Results: In separated covariate-adjusted models, childhood adversities (odds ratio [OR] = 1.16; confidence interval [CI] = [1.03, 1.30]), acute life events (OR = 1.18; CI = [1.04, 1.34]), financial strain (OR = 1.30; CI = [1.15, 1.47]), and relationship stressors (OR = 1.18; CI = [1.04, 1.35]) were associated with increased odds of obesity. In a model adjusted for all stressors simultaneously, financial strain was the only stressor independently associated with overweight (OR = 1.17; CI = [1.00, 1.36]) and obesity (OR = 1.21; CI = [1.05, 1.39]). Participants with stress exposure in the highest quintile across 2, 3, or ≥4 (compared to no) types of stressors had significantly higher odds of obesity., Conclusions: Multiple types of stressors may be risk factors for obesity, and cumulative exposure to these stressors may increase the odds of obesity. Reducing exposure to stressors at the population level may have the potential to contribute to reducing the burden of obesity., (© Society of Behavioral Medicine 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

While there is growing interest in the potential for intranasal oxytocin (IN-OT) to improve social cognition and neurocognition (ie, nonsocial cognition) in schizophrenia, the extant literature has been mixed. Here, we perform a Bayesian meta-analysis of the efficacy of IN-OT to improve areas of social and neurocognition in schizophrenia. A systematic search of original research publications identified randomized controlled trials (RCTs) of IN-OT as a treatment for social and neurocognitive deficits in schizophrenia for inclusion. Standardized mean differences (SMD) and corresponding variances were used in multilevel Bayesian models to obtain meta-analytic effect-size estimates. Across a total of 12 studies (N = 273), IN-OT did not improve social cognition (SMD = 0.07, 95% credible interval [CI] = [-0.06, 0.17]) or neurocognition (SMD = 0.12, 95% CI = [-0.12, 0.34]). There was moderate between study heterogeneity for social cognition outcomes (τs= 0.12). Moderator analyses revealed that IN-OT had a significantly larger effect on high-level social cognition (ie, mentalizing and theory of mind) compared to low-level social cognition (ie, social cue perception) (b = 0.19, 95% CI = [0.05, 0.33]). When restricting our analysis to outcomes for high-level social cognition, there was a significant effect of IN-OT (SMD = 0.20, 95 % CI = [0.05, 0.33]) but the effect was not robust to sensitivity analyses. The present analysis indicates that IN-OT may have selective effects on high-level social cognition, which provides a more focused target for future studies of IN-OT., (© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cross-cultural variability in respondent processing of survey questions may bias results from multiethnic samples. We analyzed behavior codes, which identify difficulties in the interactions of respondents and interviewers, from a discrimination module contained within a field test of the 2007 California Health Interview Survey. In all, 553 (English) telephone interviews yielded 13,999 interactions involving 22 items. Multilevel logistic regression modeling revealed that respondent age and several item characteristics (response format, customized questions, length, and first item with new response format), but not race/ethnicity, were associated with interactional problems. These findings suggest that item function within a multi-cultural, albeit English language, survey may be largely influenced by question features, as opposed to respondent characteristics such as race/ethnicity.

Measurements of neighborhood exposures likely vary depending on the definition of "neighborhood" selected. This study examined the extent to which neighborhood definition influences findings regarding spatial accessibility to tobacco retailers among youth. We defined spatial accessibility to tobacco retailers (i.e., tobacco retail density, closest tobacco retailer, and average distance to the closest 5 tobacco retailers) on the basis of circular and network buffers of 400 m and 800 m, census block groups, and census tracts by using residential addresses from the 2008 Boston Youth Survey Geospatial Dataset (n = 1,292). Friedman tests (to compare overall differences in neighborhood definitions) were applied. There were differences in measurements of youths' access to tobacco retailers according to the selected neighborhood definitions, and these were marked for the 2 spatial proximity measures (both P < 0.01 for all differences). For example, the median average distance to the closest 5 tobacco retailers was 381.50 m when using specific home addresses, 414.00 m when using census block groups, and 482.50 m when using census tracts, illustrating how neighborhood definition influences the measurement of spatial accessibility to tobacco retailers. These analyses suggest that, whenever possible, egocentric neighborhood definitions should be used. The use of larger administrative neighborhood definitions can bias exposure estimates for proximity measures.

Objectives: To advance understanding of the relationship between discrimination and sleep duration and difficulties, with consideration of multiple dimensions of discrimination, and attention to concurrent stressors; and to examine the contribution of discrimination and other stressors to racial/ ethnic differences in these outcomes., Design: Cross-sectional probability sample., Setting: Chicago, IL., Participants: There were 2,983 black, Hispanic, and white adults., Measurements and Results: Outcomes included self-reported sleep duration and difficulties. Discrimination, including racial and nonracial everyday and major experiences of discrimination, workplace harassment and incivilities, and other stressors were assessed via questionnaire. In models adjusted for sociodemographic characteristics, greater exposure to racial (β = -0.14)) and nonracial (β = -0.08) everyday discrimination, major experiences of discrimination attributed to race/ethnicity (β = -0.17), and workplace harassment and incivilities (β = -0.14) were associated with shorter sleep (P < 0.05). The association between major experiences of discrimination attributed to race/ethnicity and sleep duration (β = -0.09, P < 0.05) was independent of concurrent stressors (i.e., acute events, childhood adversity, and financial, community, employment, and relationship stressors). Racial (β = 0.04) and non-racial (β = 0.05) everyday discrimination and racial (β = 0.04) and nonracial (β = 0.04) major experiences of discrimination, and workplace harassment and incivilities (β = 0.04) were also associated with more (log) sleep difficulties, and associations between racial and nonracial everyday discrimination and sleep difficulties remained after adjustment for other stressors (P < 0.05). Racial/ethnic differences in sleep duration and difficulties were not significant after adjustment for discrimination (P > 0.05)., Conclusions: Discrimination was associated with shorter sleep and more sleep difficulties, independent of socioeconomic status and other stressors, and may account for some of the racial/ethnic differences in sleep.

Background: Race consciousness (the frequency with which one thinks about his or her own race) is a measure that may be useful in assessing whether racial discrimination negatively impacts blood pressure (BP). However, the relation between race consciousness and BP has yet to be empirically tested, especially within the context of the patient-physician relationship and medication adherence., Methods: Race-stratified generalized estimating equations were used to assess the relationship of race consciousness on BP, measures of the patient-physician relationship, and self-reported medication adherence, controlling for patients being nested within physicians and for patient age and sex., Results: The mean age of the patients was 61.3 years, 62% were black, and 65% were women. Black patients were more likely to ever think about race than were white patients (49% vs. 21%; P < 0.001). Race-conscious blacks had significantly higher diastolic BP (79.4 vs. 74.5 mm Hg; P = 0.004) and somewhat higher systolic BP (138.8 vs. 134.7 mm Hg; P = 0.13) than blacks who were not race conscious. Race-conscious whites were more likely to perceive respect from their physician (57.1% vs. 25.8%; P = 0.01) but had lower medication adherence (62.4% vs. 82.9%; P = 0.05) than whites who were not race-conscious., Conclusions: Among blacks, race consciousness was associated with higher diastolic BP. In contrast, among whites, there was no association between race consciousness and BP, but race consciousness was associated with poor ratings of adherence, despite more favorable ratings of the patient-physician relationship. Future work should explore disparities in race consciousness and its impact on health and health-care disparities., (© American Journal of Hypertension, Ltd 2013. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Psychosocial stress is a significant risk factor for smoking, and Blacks experience higher levels of psychosocial stress relative to other racial/ethnic groups. Limited research has comprehensively examined psychosocial stressors in relation to smoking among Blacks., Methods: We examined psychosocial stressors in relation to smoking status (current, previous, and never) in middle-aged Blacks (34-85 years, n = 592) from Milwaukee, Wisconsin, a subset of the Midlife in the United States Study II (2004-2006). Eleven stressor domains were assessed, including psychological and physical work stress, work-family conflict, perceived inequality, relationship stress, neighborhood stress, discrimination, financial stress, recent problems, stressful events, and childhood adversity. We also calculated a cumulative score. Multinomial models were adjusted for age, gender, education, and income., Results: Seven of the 11 stressors and the cumulative score were associated with higher odds of being a current smoker compared with a never-smoker: neighborhood, financial, relationship, and psychological work stress, perceived inequality, stressful events, childhood adversity (p values <.05; ORs ranged from 1.28 to 1.77). Three stressors and the cumulative score were associated with higher odds of being a previous smoker versus a never-smoker (p < .05). Individuals who scored in the top quartile on 5 or more stressors were 3.74 (95% CI = 2.09-6.71) times as likely to be current smokers, and more than twice as likely to be previous smokers, compared with individuals with no high stressors., Conclusions: These results demonstrate a strong relationship between stress and smoking among urban middle-aged Blacks and suggest that cessation programs should address modifiable individual and community-level stressors.

No study has yet investigated whether cortical plasticity in primary motor area (M1) is abnormal in patients with progressive supranuclear palsy (PSP). We studied M1 plasticity in 15 PSP patients and 15 age-matched healthy subjects. We used intermittent theta-burst stimulation (iTBS) to investigate long-term potentiation (LTP) and continuous TBS (cTBS) to investigate long-term depression (LTD)-like cortical plasticity in M1. Ten patients underwent iTBS again 1 year later. We also investigated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in M1 with paired-pulse transcranial magnetic stimulation, tested H reflex from upper limb flexor muscles before and after iTBS, and measured motor evoked potential (MEP) input-output (I/O) curves before and after iTBS. iTBS elicited a significantly larger MEP facilitation after iTBS in patients than in healthy subjects. Whereas in healthy subjects, cTBS inhibited MEP, in patients it significantly facilitated MEPs. In patients, SICI was reduced, whereas ICF was normal. H reflex size remained unchanged after iTBS. Patients had steeper MEP I/O slopes than healthy subjects at baseline and became even more steeper after iTBS only in patients. The iTBS-induced abnormal MEP facilitation in PSP persisted at 1-year follow-up. In conclusion, patients with PSP have abnormal M1 LTP/LTD-like plasticity. The enhanced LTP-like cortical synaptic plasticity parallels disease progression.

Background: Discrimination may be adversely associated with abdominal obesity, but few studies have examined associations with abdominal fat., Purpose: The purpose of this study was to examine whether discrimination was independently associated with visceral (VAT) and subcutaneous (SAT) fat and whether these associations differed by sex and age., Methods: Participants self-reported experiences of everyday and lifetime discrimination. The main reason for and the coping response to these experiences were also reported. VAT and SAT were quantified by computed tomography., Results: In fully adjusted models, higher reports of everyday discrimination were associated with greater SAT, but not VAT, volumes in men only: SAT increased by 3.6 (standard error = 1.8) cm(3) for each unit increase in the everyday discrimination score. In women, higher reports of lifetime non-racial discrimination were associated with greater VAT (71.6 ± 32.0, P < 0.05) and SAT (212.6 ± 83.6, P < 0.05), but these relationships were attenuated after controlling for body mass index., Conclusions: These cross-sectional findings do not fully support the independent hypothesis of discrimination and abdominal fat. Additional investigations involving longitudinal designs are warranted.

The exact pathogenesis of visual hallucinations in Parkinson's disease is not known but an integrated model has been proposed that includes impaired visual input and central visual processing, impaired brainstem regulation of sleep-wake cycle with fluctuating vigilance, intrusion of rapid eye movement dream imagery into wakefulness and emergence of internally generated imagery, cognitive dysfunction and influence of dopaminergic drugs. In a clinical study, we assessed motor and non-motor function, including sleep, mood, autonomic and global, frontal and visuoperceptive cognitive function in patients with and without visual hallucinations. A subgroup of patients underwent detailed ophthalmological assessment. In a separate pathological study, histological specimens were obtained from cases of pathologically proven Parkinson's disease and a retrospective case notes review was made for reporting of persistent formed visual hallucinations. An assessment of Lewy body and Lewy neurite pathology was carried out in five cortical regions as recommended by diagnostic criteria for dementia with Lewy Bodies and in brainstem nuclei. Ninety-four patients (mean age 67.5 ± 9.5 years) participated in the clinical study of whom 32% experienced visual hallucinations. When corrected for multiple comparisons, patients with visual hallucinations had significantly greater disease duration, treatment duration, motor severity and complications, sleep disturbances, in particular excessive daytime somnolence and rapid eye movement sleep behavioural disorder, disorders of mood, autonomic dysfunction and global, frontal and visuoperceptive cognitive dysfunction. Of the 94 patients, 50 (53%) underwent ophthalmological assessment. There were no differences in ocular pathology between the visual hallucination and non-visual hallucination groups. In a logistic regression model the four independent determinants of visual hallucinations were rapid eye movement sleep behavioural disorder (P = 0.026), autonomic function (P = 0.004), frontal cognitive function (P = 0.020) and a test of visuoperceptive function (object decision; P = 0.031). In a separate study, post-mortem analysis was performed in 91 subjects (mean age at death 75.5 ± 8.0 years) and persistent visual hallucinations were documented in 63%. Patients in the visual hallucinations group had similar disease duration but had significantly higher Lewy body densities in the middle frontal (P = 0.002) and middle temporal gyri (P = 0.033) and transentorhinal (P = 0.005) and anterior cingulate (P = 0.020) cortices but not parietal cortex (P = 0.22). Using a comprehensive assessment of the clinical, demographic and ophthalmological correlates of visual hallucinations in Parkinson's disease, the combined data support the hypothesized model of impaired visual processing, sleep-wake dysregulation and brainstem dysfunction, and cognitive, particularly frontal, impairment all independently contributing to the pathogenesis of visual hallucinations in Parkinson's disease. These clinical data are supported by the pathological study, in which higher overall cortical Lewy body counts, and in particular areas implicated in visuoperception and executive function, were associated with visual hallucinations.

A growing body of research suggests that perceived discrimination, in multiple societies, is a neglected but important predictor of increased risk of disease for a broad range of health status indicators. Several prior studies propose that discrimination is adversely related to increased cardiovascular disease risk. The studies by Hunte (Am J Epidemiol. 2011;173(11):1223-1231) and Lewis et al. (Am J Epidemiol. 2011;173(11):1232-1239) find that self-reported discrimination is associated with increased risk of adiposity for men and women. These studies highlight the potentially important role of discrimination as a risk factor for excess fat but also raise important research questions regarding the role of fat in cardiovascular disease and racial differences in these processes. More generally, they also provide an important reminder to epidemiologists and medical professionals that discrimination and other aspects of racism persist in contemporary society and that increased efforts are needed to document the extent to which they may have pathogenic consequences and to identify the most promising initiatives to reduce any observed negative effects. Equally important, these studies remind us that, although social stressors are difficult to measure accurately and comprehensively, understanding how multiple stressors combine over the life course to affect the risk of morbidity and mortality remains an important priority for concerted research attention.

The relative importance of Lewy- and Alzheimer-type pathologies to dementia in Parkinson's disease remains unclear. We have examined the combined associations of α-synuclein, tau and amyloid-β accumulation in 56 pathologically confirmed Parkinson's disease cases, 29 of whom had developed dementia. Cortical and subcortical amyloid-β scores were obtained, while tau and α-synuclein pathologies were rated according to the respective Braak stages. Additionally, cortical Lewy body and Lewy neurite scores were determined and Lewy body densities were generated using morphometry. Non-parametric statistics, together with regression models, receiver-operating characteristic curves and survival analyses were applied. Cortical and striatal amyloid-β scores, Braak tau stages, cortical Lewy body, Lewy neurite scores and Lewy body densities, but not Braak α-synuclein stages, were all significantly greater in the Parkinson's disease-dementia group (P<0.05), with all the pathologies showing a significant positive correlation to each other (P<0.05). A combination of pathologies [area under the receiver-operating characteristic curve=0.95 (0.88-1.00); P<0.0001] was a better predictor of dementia than the severity of any single pathology. Additionally, cortical amyloid-β scores (r=-0.62; P=0.043) and Braak tau stages (r=-0.52; P=0.028), but not Lewy body scores (r=-0.25; P=0.41) or Braak α-synuclein stages (r=-0.44; P=0.13), significantly correlated with mini-mental state examination scores in the subset of cases with this information available within the last year of life (n=15). High cortical amyloid-β score (P=0.017) along with an older age at onset (P=0.001) were associated with a shorter time-to-dementia period. A combination of Lewy- and Alzheimer-type pathologies is a robust pathological correlate of dementia in Parkinson's disease, with quantitative and semi-quantitative assessment of Lewy pathology being more informative than Braak α-synuclein stages. Cortical amyloid-β and age at disease onset seem to determine the rate to dementia.

Aims: The isolation and partial characterization of anti-Listeria bacteriocin producing strains present in milk from areas of northern Greece in view of their potential use as protective cultures in food fermentations., Methods and Results: Three hundred and thirty-two isolates were obtained from milk samples intended for Feta cheese production and gathered from 40 individual producers in Northern Greece. Isolates with anti-Listeria activity were identified by multiplex PCR as Enterococcus faecium and grouped by (GTG)(5) -PCR. The genomes of the anti-Listeria isolates were examined for the presence of known enterocin genes and major virulence genes by means of specific PCR. At least three known enterocin encoding genes were present in the genome of each of the 17 isolates. None of the 17 isolates harboured any of the virulence genes tested for or exhibited haemolytic activity., Conclusions: Enterococcus faecium was the dominant anti-Listeria species in the milk samples. The isolates had the potential of multiple bacteriocin production and did not exhibit some important elements of virulence., Significance and Impact of the Study: Enterococci present in milk of this area of northern Greece may be partly responsible for the safety of Feta cheese and could be useful for the production of anti-Listeria protective cultures., (© 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.)

Background: The reasons for racial/ethnic disparities in hypertension (HTN) prevalence in the United States are poorly understood., Methods: Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated whether individual- and neighborhood-level chronic stressors contribute to these disparities in cross-sectional analyses. The sample consisted of 2,679 MESA participants (45-84 years) residing in Baltimore, New York, and North Carolina. HTN was defined as systolic or diastolic blood pressure ≥140 or 90 mm Hg, or taking antihypertensive medications. Individual-level chronic stress was measured by self-reported chronic burden and perceived major and everyday discrimination. A measure of neighborhood (census tract) chronic stressors (i.e., physical disorder, violence) was developed using data from a telephone survey conducted with other residents of MESA neighborhoods. Binomial regression was used to estimate associations between HTN and race/ethnicity before and after adjustment for individual and neighborhood stressors., Results: The prevalence of HTN was 59.5% in African Americans (AAs), 43.9% in Hispanics, and 42.0% in whites. Age- and sex-adjusted relative prevalences of HTN (compared to whites) were 1.30 (95% confidence interval (CI): 1.22-1.38) for AA and 1.16 (95% CI: 1.04-1.31) for Hispanics. Adjustment for neighborhood stressors reduced these to 1.17 (95% CI: 1.11-1.22) and 1.09 (95% CI: 1.00-1.18), respectively. Additional adjustment for individual-level stressors, acculturation, income, education, and other neighborhood features only slightly reduced these associations., Conclusion: Neighborhood chronic stressors may contribute to race/ethnic differences in HTN prevalence in the United States.

The pathological findings of corticobasal degeneration are associated with several distinct clinical syndromes, and the corticobasal syndrome has been linked with a number of diverse pathologies. We have reviewed all the archival cases in the Queen Square Brain Bank for Neurological Disorders over a 20-year period with either a clinical diagnosis of corticobasal syndrome or pathological diagnosis of corticobasal degeneration in an attempt to identify the main diagnostic pitfalls. Of 19 pathologically confirmed corticobasal degeneration cases, only five had been diagnosed correctly in life (sensitivity=26.3%) and four of these had received an alternative earlier diagnosis. All five of these had a unilateral presentation, clumsy useless limb, limb apraxia and myoclonus, four had cortical sensory impairment and focal limb dystonia and three had an alien limb. Eight cases of corticobasal degeneration had been clinically diagnosed as progressive supranuclear palsy, all of whom had vertical supranuclear palsy and seven had falls within the first 2 years. On the other hand, of 21 cases with a clinical diagnosis of corticobasal syndrome, only five had corticobasal degeneration pathology, giving a positive predictive value of 23.8%; six others had progressive supranuclear palsy pathology, five had Alzheimer's disease and the remaining five had other non-tau pathologies. Corticobasal degeneration can present very commonly with a clinical picture closely resembling classical progressive supranuclear palsy or Richardson's syndrome, and we propose the term corticobasal degeneration-Richardson's syndrome for this subgroup. Cases of corticobasal degeneration-Richardson's syndrome have delayed onset of vertical supranuclear gaze palsy (>3 years after onset of first symptom) and the infrequent occurrence of predominant downgaze abnormalities, both of which can be helpful pointers to their underlying corticobasal degeneration pathology. Fourty-two per cent of corticobasal degeneration cases presented clinically with a progressive supranuclear palsy phenotype and 29% of cases with corticobasal syndrome had underlying progressive supranuclear palsy pathology. In contrast, in the Queen Square Brain Bank archival collection, corticobasal syndrome is a rare clinical presentation of progressive supranuclear palsy occurring in only 6 of the 179 pathologically diagnosed progressive supranuclear palsy cases (3%). Despite these diagnostic difficulties we conclude that corticobasal degeneration is a discrete clinicopathological entity but with a broader clinical spectrum than was originally proposed.

We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343-8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions.

The reactive changes in different types of astrocytes were analyzed in parkinsonian syndromes in order to identify common reactions and their relationship to disease severity. Immunohistochemistry was used on formalin-fixed, paraffin-embedded sections from the putamen, pons, and substantia nigra from 13 Parkinson disease (PD), 29 multiple-system atrophy (MSA), 34 progressive supranuclear palsy (PSP), 10 corticobasal degeneration(CBD), and 13 control cases. Classic reactive astrocytes were observed in MSA, PSP, and CBD, but not PD cases; the extent of reactivity correlated with indices of neurodegeneration and disease stage. Approximately 40% to 45% of subcortical astrocytes in PD and PSP accumulated alpha-synuclein and phospho-tau, respectively; subcortical astrocytes in MSA and CBD cases did not accumulate these proteins. Protoplasmic astrocytes were identified from fibrous astrocytes by their expression of parkin coregulated gene and apolipoprotein D, and accumulated abnormal proteins in PD, PSP, and CBD, but not MSA. The increased reactivity of parkin coregulated gene-immunoreactive protoplasmic astrocytes correlated with parkin expression in PSP and CBD. Nonreactive protoplasmic astrocytes were observed in PD and MSA cases; in PD, they accumulated alpha-synuclein, suggesting that the attenuated response might be due to an increase in the level of alpha-synuclein. These heterogeneous astroglial responses in PD, MSA, PSP, and CBD indicate distinct underlying pathogenic mechanisms in each disorder.

Prognostic predictors have not been defined for progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Subtypes of both disorders have been proposed on the basis of early clinical features. We performed a retrospective chart review to investigate the natural history of pathologically confirmed cases of PSP and MSA. Survival data and several clinically relevant milestones, namely: frequent falling, cognitive disability, unintelligible speech, severe dysphagia, dependence on wheelchair for mobility, the use of urinary catheters and placement in residential care were determined. On the basis of early symptoms, we subdivided cases with PSP into 'Richardson's syndrome' (RS) and 'PSP-parkinsonism' (PSP-P). Cases of MSA were subdivided according to the presence or absence of early autonomic failure. Sixty-nine (62.7%) of the 110 PSP cases were classified as RS and 29 (26.4%) as PSP-P. Of the 83 cases of MSA, 42 (53.2%) had autonomic failure within 2 years of disease onset. Patients with PSP had an older age of onset (P < 0.001), but similar disease duration to those with MSA. Patients with PSP reached their first clinical milestone earlier than patients with MSA (P < 0.001). Regular falls (P < 0.001), unintelligible speech (P = 0.04) and cognitive impairment (P = 0.03) also occurred earlier in PSP than in MSA. In PSP an RS phenotype, male gender, older age of onset and a short interval from disease onset to reaching the first clinical milestone were all independent predictors of shorter disease duration to death. Patients with RS also reached clinical milestones after a shorter interval from disease onset, compared to patients with PSP-P. In MSA early autonomic failure, female gender, older age of onset, a short interval from disease onset to reaching the first clinical milestone and not being admitted to residential care were independent factors predicting shorter disease duration until death. The time to the first clinical milestone is a useful prognostic predictor for survival. We confirm that RS had a less favourable course than PSP-P, and that early autonomic failure in MSA is associated with shorter survival.

The authors investigated whether substance use and self-reported racial discrimination were associated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Smoking status, alcohol consumption, and lifetime use of marijuana, amphetamines, and opiates were ascertained in 2000-2001, 15 years after baseline (1985-1986). Most of the 1,507 African Americans reported having experienced racial discrimination, 79.5% at year 7 and 74.6% at year 15, compared with 29.7% and 23.7% among the 1,813 Whites. Compared with African Americans experiencing no discrimination, African Americans reporting any discrimination had more education and income, while the opposite was true for Whites (all p < 0.001). African Americans experiencing racial discrimination in at least three of seven domains in both years had 1.87 (95% confidence interval (CI): 1.18, 2.96) and 2.12 (95% CI: 1.42, 3.17) higher odds of reporting current tobacco use and having any alcohol in the past year than did their counterparts experiencing no discrimination. With control for income and education, African Americans reporting discrimination in three or more domains in both years had 3.31 (95% CI: 1.90, 5.74) higher odds of using marijuana 100 or more times in their lifetime, relative to African Americans reporting no discrimination. These associations were similarly positive in Whites but not significant. Substance use may be an unhealthy coping response to perceived unfair treatment for some individuals, regardless of their race/ethnicity.

Patients with Parkinson's disease who develop disabling levodopa-induced motor fluctuations have a stronger therapeutic response than those who experience a more modest but stable response. A difference in the histopathological lesion between the two groups might be responsible. Case records from 97 patients with pathologically proven Parkinson's disease were reviewed to determine the pattern of levodopa response. Pathological findings for fluctuating and non-fluctuating cases were compared. Patients with motor fluctuations had a younger age of onset and longer disease course (P < 0.001), although mean age at death was almost the same. Four milestones of advanced disease (frequent falls, visual hallucinations, cognitive disability and need for residential care) occurred at a similar time from death in each group; this interval was not proportionate to the disease duration. There were no significant differences in the severity or distribution of Lewy body or other pathologies. Irrespective of the pattern of levodopa response, patients reach a common pathological endpoint at a similar age, and the duration and manifestations of end-stage disease are alike. A non-linear or exponential time relationship may govern the late clinical and pathological progression of Parkinson's disease.

Clinical syndromes associated with progressive supranuclear palsy-tau pathology now include progressive supranuclear palsy-parkinsonism (PSP-P), in addition to classic Richardson's syndrome (RS) and pure akinesia with gait freezing (PAGF). Although pathological heterogeneity of progressive supranuclear palsy (PSP) has also been established, attempts to correlate this with clinical findings have only rarely provided conclusive results. The aim of this study was to investigate whether regional variations in the types of tau lesions or differences in overall tau load may explain the clinical differences between the RS, PSP-P and PAGF. Quantitative tau pathology assessment was performed in 17 brain regions in 42 cases of pathologically diagnosed PSP (22 RS, 14 PSP-P and 6 PAGF). Neurofibrillary tangles, tufted astrocytes, coiled bodies and thread pathology were quantitated and a grading system was developed separately for each region. Using these grades the overall tau load was calculated in each case. To establish a simplified system for grading the severity of tau pathology, all data were explored to identify the minimum number of regions that satisfactorily summarized the overall tau severity. The subthalamic nucleus, substantia nigra and globus pallidus were consistently the regions most severely affected by tau pathology. The mean severity in all regions of the RS group was higher than in PSP-P and PAGF, and the overall tau load was significantly higher in RS than in PSP-P (P = 0.002). Using only the grade of coiled body + thread lesions in the substantia nigra, caudate and dentate nucleus, a reliable and repeatable 12-tiered grading system was established (PSP-tau score: 0, mild tau pathology, restricted distribution; >7, severe, widespread tau pathology). PSP-tau score was negatively correlated with disease duration (Spearman's rho -0.36, P = 0.028) and time from disease onset to first fall (Spearman's rho -0.49, P = 0.003). The PSP-tau score in PSP-P (median 3, range 0-5) was significantly lower than in RS (median 5, range 2-10, Mann-Whitney U, P < 0.001). The two cases carrying the tau-H2 protective allele had the two lowest PSP-tau scores. We have identified significant pathological differences between the major clinical syndromes associated with PSP-tau pathology and the restricted, mild tau pathology in PSP-P supports its clinical distinction from RS. The grading system we have developed provides an easy-to-use and sensitive tool for the morphological assessment of PSP-tau pathology and allows for consideration of the clinical diversity that is known to occur in PSP.

Normative neuropsychological data for U.S. racial/ethnic minorities are limited. Extant norms are based on small, regional groups that may not be nationally representative. The objectives of this study were to (1) provide norms for a modified Symbol Digit Modalities Test (M-SDMT) based on a nationally representative sample of African Americans, Caribbean Blacks, and non-Latino Whites (NLW) living in areas with large populations of Blacks; and (2) determine significant correlates of M-SDMT performance. The M-SDMT was administered to a subset of respondents from the National Survey of American Life in standard face-to-face interviews. M-SDMT performance was influenced by race/ethnicity, age, education, and gender. African Americans and NLW groups had similar M-SDMT performances, which differed from Caribbean Blacks. The Black ethnic differences in M-SDMT were not explained by the sociodemographic factors considered in this study. Unlike previous work, this study supports the consideration of Black ethnicity when evaluating Black neuropsychological test performance.

The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification of characteristic signs and symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and to compare the biochemical and genetic characteristics of these groups. In 103 consecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson's syndrome (RS) and PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54% of all cases, and were characterized by the early onset of postural instability and falls, supranuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32%) were characterized by asymmetric onset, tremor, a moderate initial therapeutic response to levodopa and were frequently confused with Parkinson's disease (PSP-P). Fourteen cases (14%) could not be separated according to these criteria. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 years, P < 0.001) and age at death earlier (72.1 versus 75.5 years, P = 0.01) than in PSP-P. The isoform composition of insoluble tangle-tau isolated from the basal pons also differed significantly. In RS, the mean four-repeat:three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P < 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical subgroups was not significant. There were no differences in apolipoprotein E genotypes. The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of cases in this series of pathologically confirmed cases. We propose that PSP-P represents a second discrete clinical phenotype that needs to be clinically distinguished from classical PSP (RS). The different tau isoform deposition in the basal pons suggests that this may ultimately prove to be a discrete nosological entity.

The study reported in this article examined the prevalence of mental health disorders and the sociodemographic factors associated with having a mental health disorder in a probability sample of 185 African American and white single mothers. Logistic regression analyses revealed that race (being white) and being on welfare were associated with increased risk of having a mental health disorder, when controlling for other sociodemographic variables. The association of welfare status and psychiatric disorders highlights the need for access to mental health services for this population. Implications for low-income women making the transition from welfare to employment are discussed.

Background: This qualitative study aimed to explore the views of key stakeholders regarding the role that public health professionals have or should have in the provision of effective health care within the National Health Service., Methods: A national (England) questionnaire survey generated a sample for qualitative telephone interviews and two site case studies. The interviews were conducted in three stages: first, 27 interviews were based on assessed reported levels of organizational activity, including non-respondents; next, views in six areas were consolidated by extra interviews; finally, two extra areas were visited for individual and group interviews. The interviews were analysed for salient themes., Results: There was a widespread view that public health had not delivered its potential. Many Trusts currently wanted public health to have influence over commissioning, provide health needs assessments and epidemiological skills, and provide a strategic focus and unbiased advice. Evaluation of actual activity varied widely; local history and congruent personalities seemed to be associated with perceived success. In some cases there was mutual suspicion between Health Authorities and Trusts. Public health was often perceived by Trusts to have been marginalized. This perception was not shared by Public Health Consultants, who highlighted lack of resources as a reason for lack of involvement. The contribution of public health professionals working in Trusts was highly regarded. Barriers included overcoming initial prejudice and combating isolation within Trusts. There were four categories of response in respect of the potential future role for public health in implementing effective health care: no role; collaborative working between Health Authority Public Health Departments and Trusts; deployment of public health workers within Trusts, and an undecided group. Overall, the skills of public health, especially strategic vision and population perspectives, were seen as valuable but as yet unrealized., Conclusions: Public health skills (but not necessarily professionals) may be valuable in implementing effective health care in Trusts. However, public health professionals must refocus and market their skills to Trusts if the discipline is to play a key role in this task.

Substances in the faeces of house dust mites are well-recognized as common allergens in the pathogenesis of asthma. There have been many trials of interventions aimed at reducing mite populations in the home, but most have been uncontrolled, too small, or too short to determine with confidence any beneficial effects. Of those which succeeded, very few used methods which reduced mite populations on a permanent basis. House dust mites are sensitive to humidity. Their geographical distribution is closely correlated to the availability of moisture. Very little work has been done on the effects of reducing humidity in the home environment in the long term, with a view to controlling dust mite populations. Two different methods which might reduce humidities to levels which could successfully reduce dust mite numbers are dehumidifiers, and mechanical ventilation with heat recovery (MVHR). To date there has been no work assessing the effectiveness of dehumidifiers and very little (although promising) work on MVHR. We discuss the potential of humidity control as an adjunct to the clinical treatment of asthma.

Recent requirements of the GP contract have included the testing of random urine samples from all patients aged 16-75 years for glycosuria. As a means of detecting diabetes this will be both inefficient and wasteful of resources, because of the method employed and age group screened. We examined a simple method for screening large populations for non-insulin-dependent diabetes mellitus using self-testing for post-prandial glycosuria, and compared its performance to that using fasting plasma glucose and haemoglobin A1. The study involved five general practices, screening over 13,000 subjects aged between 45 and 70 years. Of the 13,795 subjects screened, 10,348 responded (75%). Glycosuria was detected in 343 subjects (3.3%), of whom 330 (95.9%) attended for oral glucose tolerance testing. Of these 99 (30%) had newly diagnosed diabetes, 56 (17%) had impaired glucose tolerance. A further 65 subjects were identified as having diabetes but were not on a register of cases. Prevalence of diabetes in this age group rose from 2.26% to 4.1%. In a normal population control group (442 subjects from Ely), this system gave a sensitivity of 43%, specificity of 98% and positive predictive value of 53%, and compared favourably to the use of a fasting plasma glucose of 6 mmol/l, which gave a sensitivity of 65%, but only a specificity of 64% and positive predictive value of 9%. These results support the use of this simple system in large population screening for diabetes.

The KorB protein of broad-host-range plasmid RK2 is a transcriptional repressor involved in the control of genes for plasmid replication, conjugative transfer and stable maintenance. We have purified this protein close to homogeneity from cells harbouring an overexpression vector with the korB gene under the control of the tac promoter. KorB binds to restriction fragments bearing its proposed operator sequence, OB. Its interaction with this palindromic site was confirmed by DNaseI or hydroxyl radical footprinting at two OB sequences from RK2. Comparisons showed that the OB context affects the nature of the footprint. Our evidence suggests that KorB is a tetramer. As such, it may be able to bind two sites simultaneously on the same or on different DNA molecules. Using the korABF promoter, which is subject to KorB repression, we demonstrate by footprinting and restriction protection that KorB and RNA polymerase can bind simultaneously. Permanganate footprinting showed that KorB represses this promoter by preventing isomerization of the RNA polymerase-promoter complex from the closed to open form.

The Coventry Diabetes Study compared the prevalence of diabetes and impaired glucose tolerance in adult Asians and Europids in relation to age, sex and body mass index. The study involved a cross-sectional house to house screening for diabetes in the electoral ward of Foleshill, Coventry, a traditional area for migration into the city. Subjects with a high blood glucose and 10 per cent of others were referred for a 75 g oral glucose tolerance test. Of the 10,304 adult residents aged 20 years or above, 3529 (64 per cent) of 5508 Europids and 3692 (84 per cent) of 4395 Asians were either screened for diabetes or already diabetic and 719 (65 per cent) of 1114 Europids and 780 (72 per cent) of 1084 Asians invited to glucose tolerance test attended. Although the prevalence of insulin-dependent diabetes was similar, the age-adjusted prevalence of non-insulin-dependent diabetes was 3.2 per cent (95 per cent confidence interval (CI): 2.6-4.0) and 4.7 per cent (CI per cent 4.0-5.5) in Europid males and females but 12.4 per cent (CI 11.0-13.8) and 11.2 CI per cent (10.0-12.5) in Asian males and females giving prevalence ratios of 3.9 per cent (3.1-5.0) in males and 2.4 per cent (2.0-2.9) in females. These differences were not due to differences in body mass index. The prevalence of impaired glucose tolerance was also higher in Asians aged below 60 years, and in 65 per cent of Europids and 40 per cent of Asians non-insulin-dependent diabetes was previously undiagnosed. The non-insulin-dependent diabetes/impaired glucose tolerance ratio was significantly higher in Asians than Europids. Non-insulin-dependent diabetes in Asians differs from that in Europids. Besides the higher overall prevalence, there is a greater proportion of males, a lower proportion undiagnosed disease, a younger age at diagnosis and a greater proportion of abnormal glucose tolerance that is due to non-insulin-dependent diabetes.

The prevalence of diabetes mellitus in 557 patients with granuloma annulare (GA) has been assessed by a retrospective study, using age-matched population data. A definite association was confirmed between GA and insulin-dependent diabetes with 16 observed cases compared with 0.9 expected, and in all but one case the diabetes was associated with the localized form of GA. Two further cases developed insulin-dependent diabetes within 5 years of presentation with GA.

The continuing care of people with epilepsy in two general practices was investigated by means of case note review and interviews with patients. It was found that 98% (56 out of 57) of patients were receiving anticonvulsant drugs. Despite the prescription of drugs, however, only 64% (25 out of 39) of those patients interviewed were receiving regular follow-up and three of the patients receiving no surveillance had suffered recent fits. Many of the patients had experienced no fits for several years and it was considered that anticonvulsant therapy could have been stopped in some cases. It is recommended that a system be devised to ensure that all epileptic patients on anticonvulsants see their general practitioner at least yearly.

Minimizing the need for hospital admissions for hyperglycaemic coma, hypoglycaemic coma and amputation of the lower limbs in patients with diabetes can be regarded as some of the legitimate objectives of a local diabetes service. Routinely collected data are available to calculate rates for such admissions for health service districts and for regions or their equivalents. East Anglian regional rates for admissions mentioning hyperglycaemic coma fell between 1981 and 1986 while rates for those mentioning hypoglycaemic coma rose. Amputation rates remained steady. Between-district variation for all rates was considerable and certain districts showed consistently high rates from year to year for hyperglycaemic coma with others having consistently high rates for amputations. Lack of standardization of case definition and uncertainty about the validity of routinely collected hospital admission data are the most important drawbacks of this approach. With careful interpretation, however, these data provide a possible source for the measurement of the effectiveness of local diabetes services.

The hypothesis that undescended testis is caused by an excess of maternal oestrogen in pregnancy has been tested indirectly in a case-control study comparing mothers of boys with undescended testis (83) and mothers of normal boys (129) born on the same day. The study concentrated on the gestation of the boys, but also investigated the mother's previous obstetric history and postnatal events in the boys. The hypothesis predicted that there should be an excess of nausea, vomiting and hypertension in mothers of cases, but in fact the pregnancies of the case and control mothers were similar in all respects except one. The exception was the increased liability of the mothers of cases to threatened abortion. Mothers of cases also had an increased tendency to miscarry in previous conceptions, a reduced number of deliberate terminations and evidence of decreased fertility. An alternative hypothesis is suggested which would explain these findings. This is that placental function is impaired in the gestation of affected boys and the secretion of human chorionic gonadotrophin is reduced. This leads to changes in fetal testicular function and possible maldescent. Those born with undescended testis were more likely to present to a general practitioner with illness in the first three years after birth and this difference was mainly due to asthma, eczema, jaundice and feeding difficulties.

Antisera to human oral epithelial cells were produced in rabbits and found to be specific for epithelial type cells of man, guinea-pig and rabbit. Binding of the antisera to human oral epithelial cells was not affected by pre-incubation in concanavalin A, trypsin or neuraminidase, nor by pre-incubation of the antisera with fetuin. The antisera would appear to differ from pemphigus antiserum.