The role of neighborhood social cohesion in the association between seeing people walk and leisure-time walking among Latino adults.

Few studies have investigated the association between seeing people walk and leisure-time walking, and the role of neighborhood social cohesion among Latinos/Latinx. We examined the association between frequency of seeing people walk within sight of home and leisure-time walking, and whether neighborhood social cohesion explained this association. We utilized cross-sectional data from the 2015 National Health Interview Survey from Latinos aged 18+ years (n=4,669). A structural equation model was used to estimate the association between seeing people walk and leisure-time walking, and to test the extent to which neighborhood social cohesion accounted for the association. Findings indicate that there is a strong association between seeing people walk and leisure-time walking, and neighborhood social cohesion partially explains this association among Latinos/Latinx. Neighborhood social cohesion may strengthen efforts focused on neighborhood-level behavioral norms that promote walking.

Neighborhood Walkability and Overweight/Obese Weight Status Among Latino Adults.

PURPOSE: To examine whether aerobic physical activity mediates the association between neighborhood walkability and overweight/obesity weight status among Latino adults and whether the relative contribution of this pathway linking neighborhood walkability and aerobic activity varies by level of neighborhood social cohesion. DESIGN: Cross-sectional. SETTING: National Health Interview Survey (NHIS) 2015. SAMPLE: NHIS adult Latino participants ≥18 years of age (n = 4303). MEASURES: Neighborhood walkability, neighborhood social cohesion, body mass index, and aerobic physical activity. ANALYSIS: To determine whether physical activity mediates the relationship of walkability with overweight/obese weight status, a simple mediation analysis was conducted. Additionally, a moderated mediation analysis was conducted to test whether neighborhood social cohesion had a moderating effect on this relationship. RESULTS: On average, the sample was 41 years old, 51% were male, 34% had less than a high school education, and 57% were foreign-born. Neighborhood walkability was statistically significantly related to overweight/obese weight status (standardized effect= -0.05, standard error [SE] = 0.02, P = .01). The interaction between walkability and neighborhood social cohesion on physical activity was not significant (standardized effect = 0.06, SE = 0.03, P = .09). Thus, the indirect effect of walkability on overweight/obesity weight status through physical activity was not shown to be modified by neighborhood social cohesion. CONCLUSION: Other neighborhood environment factors may play a role in the contribution of neighborhood walkability to overweight/obese weight status among Latinos.

Neighborhood Walkability and Aerobic Physical Activity among Latinos.

Objective: In this study, we examined neighborhood social cohesion (NSC) as a moderator in the association between neighborhood walkability and meeting the aerobic physical activity guideline among US Latino adults. Methods: We used 2015 National Health Interview Survey cross-sectional data from 4525 adult US Latino participants ≥18 years of age. NSC and walkability measures were self-reported. Higher walkability scores indicating higher walkability. Aerobic activity was assessed based on self-reported frequency and duration of activity. Minutes per week of moderate and vigorous aerobic activity were then categorized based on the 2018 Physical Activity Guidelines for Americans. Survey logistic regression was used to compute odds ratios [OR] and 95% confidence intervals [CI]. Effect modification by neighborhood social cohesion was tested by inclusion of a walkability*NSC interaction term. Results: A one-unit higher walkability score was associated with higher odds of meeting the aerobic activity guideline (OR = 1.06; 95% CI: 1.02, 1.11). After adding NSC to the model, the association remained statistically significant (OR = 1.05; 95% CI: 1.01, 1.10). The walkability*NSC interaction term was not statistically significant. Conclusions: NSC did not moderate the association between neighborhood walkability and meeting the aerobic activity guideline among US Latino adults.

Food insecurity and adult overweight/obesity: Gender and race/ethnic disparities.

The majority of the food insecurity-obesity research has indicated a positive association among women, especially minority women. Less research has been conducted on men, and the findings are inconsistent. The aim was to assess whether gender and race/ethnic disparities exists between the food insecurity and overweight/obesity relationship among adults ages 18-59. We used the cross-sectional 2011 and 2012 National Health Interview Survey data (N = 19,990). Three or more affirmative responses on the 10-item USDA Food Security Scale indicated food insecure experiences. Self-reported height and weight were used to calculate body mass index according to the Centers for Disease Control and Prevention. Multivariate logistic regression models were stratified by gender and race/ethnicity to estimate the association between food insecurity and overweight/obesity controlling for several demographic characteristics. Adults on average were 36 years of age (51% female; 56% white, 27% Hispanic, and 17% black), 27% were food insecure, and 65% were overweight/obese. Food insecurity was most prevalent among blacks and Hispanics, regardless of gender. A greater percentage of food insecure women were overweight/obese compared to food secure women among all race/ethnicity groups; while similar proportions of white, black, and Hispanic men were overweight/obese irrespective of their food security status. In covariate-adjusted models, food insecurity was associated with a 41% and 29% higher odds of being overweight/obese among white and Hispanic women, respectively. Food insecurity was not related to overweight/obesity among black women nor among white, black, and Hispanic men. The complex relationship between food insecurity and obesity suggests a need to investigate potential behavioral and physiological mechanisms, and moderators of this relationship.

Food Insecurity and Pre-diabetes in Adults: Race/Ethnic and Sex Differences.

OBJECTIVE: We examined sex and race/ethnicity differences in the association between food insecurity status and prediabetes among adults. METHOD: We used cross-sectional 2011 and 2012 National Health Interview Survey data on non-Hispanic white, non-Hispanic black, and Hispanic adults aged 18-59 years whose household income was ≤ 299% Federal Poverty Line (N = 19,048). Food insecurity status was determined by 3 or more affirmative responses on the 10-item USDA Food Security Scale. Pre-diabetes was self-reported. Logistic regression analyses were used to estimate associations of food insecurity with pre-diabetes and adjusted for several demographic characteristics. All models were stratified by sex and race/ethnicity. RESULTS: In adjusted models, food insecure non-Hispanic white women and non-Hispanic black women had 53% and over 200% higher odds of being pre-diabetic, respectively. Food insecurity was not related to pre-diabetes for Hispanic women or men. CONCLUSION: Limited food resources appear to place non-Hispanic white and non-Hispanic black women at risk for pre-diabetes. Linking food assistance programs with community-based health education programs may be a comprehensive approach to support those who are food insecure with diabetes prevention.

Comparison of a New Intranasal Naloxone Formulation to Intramuscular Naloxone: Results from Hypothesis-generating Small Clinical Studies.

Easy-to-use naloxone formulations are needed to help address the opioid overdose epidemic. The pharmacokinetics of i.v., i.m., and a new i.n. naloxone formulation (2 mg) were compared in six healthy volunteers. Relative to i.m. naloxone, geometric mean (90% confidence interval [CI]) absolute bioavailability of i.n. naloxone was modestly lower (55%; 90% CI, 43-70% vs. 41%; 90% CI, 27-62%), whereas average (±SE) mean absorption time was substantially shorter (74 ± 8.8 vs. 6.7 ± 4.9 min). The opioid-attenuating effects of i.n. naloxone were compared with i.m. naloxone (2 mg) after administration of oral alfentanil (4 mg) to a separate group of six healthy volunteers pretreated with 240 mL of water or grapefruit juice. The i.m. and i.n. naloxone attenuated miosis by similar extents after water (40 ± 15 vs. 41 ± 21 h*%) and grapefruit juice (49 ± 18 vs. 50 ± 22 h*%) pretreatment. Results merit further testing of this new naloxone formulation.

Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus.

We aimed to evaluate the pharmacodynamics, efficacy, safety and tolerability of the JAK1 inhibitor GSK2586184 in adults with systemic lupus erythematosus (SLE). In this adaptive, randomized, double-blind, placebo-controlled study, patients received oral GSK2586184 50-400 mg, or placebo twice daily for 12 weeks. Primary endpoints included interferon-mediated messenger RNA transcription over time, changes in Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index score, and number/severity of adverse events. A pre-specified interim analysis was performed when ≥ 5 patients per group completed 2 weeks of treatment. In total, 84-92% of patients were high baseline expressors of the interferon transcriptional biomarkers evaluated. At interim analysis, GSK2586184 showed no significant effect on mean interferon transcriptional biomarker expression (all panels). The study was declared futile and recruitment was halted at 50 patients. Shortly thereafter, significant safety data were identified, including elevated liver enzymes in six patients (one confirmed and one suspected case of Drug Reaction with Eosinophilia and Systemic Symptoms), leading to immediate dosing cessation. Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index scores were not analysed due to the small number of patients completing the study. The study futility and safety data described for GSK2586184 do not support further evaluation in patients with SLE. Study identifiers: GSK Study JAK115919; ClinicalTrials.gov identifier: NCT01777256.

Quantitative prediction and clinical evaluation of an unexplored herb-drug interaction mechanism in healthy volunteers.

Quantitative prediction of herb-drug interaction risk remains challenging. A quantitative framework to assess a potential interaction was used to evaluate a mechanism not previously tested in humans. The semipurified milk thistle product, silibinin, was selected as an exemplar herbal product inhibitor of raloxifene intestinal glucuronidation. Physiologically based pharmacokinetic (PBPK) model simulations of the silibinin-raloxifene interaction predicted up to 30% increases in raloxifene area under the curve (AUC0-inf) and maximal concentration (Cmax). Model-informed clinical evaluation of the silibinin-raloxifene interaction indicated minimal clinical interaction liability, with observed geometric mean raloxifene AUC0-inf and Cmax ratios lying within the predefined no effect range (0.75-1.33). Further refinement of PBPK modeling and simulation approaches will enhance confidence in predictions and facilitate generalizability to additional herb-drug combinations. This quantitative framework can be used to develop guidances to evaluate potential herb-drug interactions prospectively, providing evidenced-based information about the risk or safety of these interactions.

Assessing adherence in Thai patients taking combination antiretroviral therapy.

In settings where medications and viral load (VL) monitoring are limited by cost, clinicians need reliable ways to assess patient adherence to therapy. We assessed sensitivity and specificity of two self-reported adherence tools (a visual analogue scale [VAS] and the CASE [Center for Adherence Support Evaluation] adherence index), against a standard of detectable VL, with 288 patients from three sites in Thailand. We also assessed predictors of non-adherence. The sensitivity and specificity of the VAS <95% and CASE adherence index ≤11 against a VL >50 copies/mL were 26% and 90%, 19% and 95%, respectively. Against a VL ≥1000 copies/mL sensitivities increased to 55% and 36%, respectively, and specificities were unchanged. Attending a clinic not staffed by HIV specialists (odds ratio [OR] 3.14; 95% confidence interval [CI] 1.19-8.34) and being educated to primary school level or less (OR 2.24; 95% CI 1.01-4.94) were associated with self-reported adherence <95% on the VAS in multivariate analysis. Adherence assessed by the VAS was a more accurate predictor of detectable VL. Policy-makers in resource-limited settings should ensure that treatment centres are staffed with well-trained personnel aware of the importance of good patient adherence.

Recruitment of adenomatous polyposis coli and beta-catenin to axin-puncta.

The adenomatous polyposis coli (APC) tumour suppressor is a multifunctional protein involved in the regulation of Wnt signalling and cytoskeletal dynamics. Little is known about how APC controls these disparate functions. In this study, we have used APC- and axin-fluorescent fusion proteins to examine the interactions between these proteins and show that the functionally distinct populations of APC are also spatially separate. Axin-RFP forms cytoplasmic punctate structures, similar to endogenous axin puncta. Axin-RFP recruits beta-catenin destruction complex proteins, including APC, beta-catenin, glycogen synthase kinase-3-beta (GSK3-beta) and casein kinase-1-alpha (CK1-alpha). Recruitment into axin-RFP puncta sequesters APC from clusters at cell extensions and this prevents its microtubule-associated functions. The interaction between APC-GFP and axin-RFP within the cytoplasmic puncta is direct and dramatically alters the dynamic properties of APC-GFP. However, recruitment of APC to axin puncta is not absolutely required for beta-catenin degradation. Instead, formation of axin puncta, mediated by the DIX domain, is required for beta-catenin degradation. An axinDeltaDIX mutant did not form puncta, but still mediated recruitment of destruction complex proteins and phosphorylation of beta-catenin. We conclude that there are distinct pools of APC and that the formation of axin puncta, rather than the axin/APC complex, is essential for beta-catenin destruction.

British Society for Haematology, Slide session, Annual Scientific Meeting, Bournemouth, 2007.

Eight cases discussed by experts at the 2007 Annual Scientific Meeting of the British Society of Haematology are presented as at the meeting, with a discussion of the morphological features, digital information and differential diagnosis being followed by further information and a final diagnosis. Additionally, digital slides of two of the cases were available to be viewed by the internet with the opportunity for delegates to suggest diagnoses.

A method for introducing non-silencing siRNA into the guinea pig cochlea in vivo.

The aim of this preliminary study was to establish the methodology by which siRNA can be introduced into the adult guinea pig cochlea in vivo whilst preserving auditory function with a view to using targeted siRNAs to knockdown genes essential for auditory transduction. Initially a fluorescently tagged non-silencing siRNA complexed with a lipid-based transfection reagent was introduced into the perilymphatic compartment of the cochlea. Although auditory function was fully preserved, siRNA uptake was only observed in cells lining the perilymphatic space that are not critically involved in auditory transduction and therefore of little interest. Another approach was therefore adopted, in which siRNA was introduced directly into the scala media (endolymphatic compartment) of the apical (fourth) cochlear turn by slow pressure injection. During endolymphatic perfusion, the endocochlear potential (EP) and compound action potential (CAP) thresholds for basal turn frequencies from 6 to 20 kHz could be preserved, while CAP thresholds for 1-4 kHz were often elevated by 10-20 dB. CAP thresholds and EP were preserved 24 and 48 h after perfusion in some animals but reduced in others. siRNA uptake was observed predominantly in marginal and intermediate cells of the stria vascularis in all cochlear turns but not in cells of the organ of Corti.

A recurring outbreak of Shigella sonnei among traditionally observant Jewish children in New York City: the risks of daycare and household transmission.

Dispersed community outbreaks of Shigella sonnei have occurred cyclically among traditionally observant Jews in the United States. In February 2000, we investigated a S. sonnei outbreak in one Jewish community in New York City. To determine risk factors for introduction of infection into households, we conducted a cohort study of households to compare risk factors for illness among primary subjects within households and age-matched well siblings. Isolates were subtyped by pulsed-field gel electrophoresis (PFGE). We used a random effects model to assess extra-household vs. intra-household transmission in households with multiple ill household members. Daycare or pre-school attendance [matched odds ratio (mOR) 16.1, P<0.001] and age <60 months (mOR 6.3, P<0.001) were independently associated with index subject illness. Outbreak isolates were closely related by PFGE analysis to the strain previously observed in Jewish community outbreaks. The random effects model strongly indicated that multiple illnesses in a single household are due to secondary transmission. Disease containment efforts should focus on reducing Shigella transmission in childcare settings and within homes.

New haplotype for the Glu104Asp mutation in triose-phosphate isomerase deficiency and prenatal diagnosis in a Spanish family.

First-trimester prenatal diagnosis was undertaken by chorionic villus DNA analysis in a Spanish family with the inherited Glu104Asp triose-phosphate isomerase deficiency. The fetus was heterozygous for the mutation and therefore predicted to be clinically unaffected. To investigate the evolutionary origin of this mutation, studies were conducted on the intragenic 2262A/G polymorphism and the CD4 pentameric tandem repeat marker. A different haplotype was found to the one previously described, suggesting a different origin of the Spanish mutation.

A simple method allowing DIC imaging in conjunction with confocal microscopy.

Current optical methods to collect Nomarski differential interference contrast (DIC) or phase images with a transmitted light detector (TLD) in conjunction with confocal laser scanning microscopy (CLSM) can be technically challenging and inefficient. We describe for the first time a simple method that combines the use of the commercial product QPm (Iatia, Melbourne Australia) with brightfield images collected with the TLD of a CLSM, generating DIC, phase, Zernike phase, dark-field or Hoffman modulation contrast images. The brightfield images may be collected at the same time as the confocal images. This method also allows the calculation of contrast-enhanced images from archival data. The technique described here allows for the creation of contrast-enhanced images such as DIC or phase, without compromising the intensity or quality of confocal images collected simultaneously. Provided the confocal microscope is equipped with a motorized z-drive and a TLD, no hardware or optical modifications are required. The contrast-enhanced images are calculated with software using the quantitative phase-amplitude microscopy technique (Barone-Nugent et al., 2002). This technique, being far simpler during image collection, allows the microscopist to concentrate on their confocal imaging and experimental procedures. Unlike conventional DIC, this technique may be used to calculate DIC images when cells are imaged through plastic, and without the use of expensive strain-free objective lenses.

Elevated erythrocyte CDP-choline levels associated with beta-thalassaemia in patients with transfusion independent anaemia.

The accumulation of CDP-ethanolamine as well as CDP-choline in a small cohort of patients with normal UMPH1 and no defined cause for their anaemia suggested a defect in both phosphotransferases. Here we report 10 patients with transfusion independent beta-thalassaemia; 8 being pure heterozygotes and 2 heterozygotes also for Hb E. Mean CDP-choline (86.xxx +/- 48 microM) and CDP-ethanolamine (34.6 microM +/- 34.5 microM), mean control <3 microM. Elevated CDP-choline in patients with no defined cause for their haemolytic anaemia was previously suggested as a possible indicator of CDP-choline phosphotransferase deficiency. Here we associate it with transfusion independent beta-thalassaemia.

Report on slide session, British Society for Haematology, 43rd Annual Scientific Meeting, Glasgow, 2003.

Seven patients who had a diagnostic problem were presented at the British Society for Haematology, Annual Scientific Meeting in 2003. The likely diagnosis was discussed on the basis of a synopsis of the history and blood film and trephine biopsy features and forms the basis of this report. Diagnostic problems dealt with included lymphoproliferative and myeloproliferative disorders and haemolytic anaemia.

Field investigations of emergency department syndromic surveillance signals--New York City.

INTRODUCTION: The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has operated a syndromic surveillance system based on emergency department (ED) chief-complaint data since November 2001. This system was created for early detection of infectious-disease outbreaks, either natural or intentional. However, limited documentation exists regarding epidemiologic field investigations conducted in response to syndromic surveillance signals. OBJECTIVE: DOHMH conducted field investigations to characterize syndromic surveillance signals by person, place, and time and to determine whether signals represented true infectious-disease outbreaks. METHODS: A DOHMH physician reviews ED-based syndromic surveillance results daily to look for signals. When necessary, field investigations are conducted and consist of a review of the patient line list, telephone interviews with hospital staff, chart reviews, interviews with patients, and collection and testing of specimens. RESULTS: In November 2002, a series of citywide signals for diarrhea and vomiting syndromes, which coincided with institutional outbreaks consistent with viral gastroenteritis, prompted DOHMH to send mass e-mail notification to NYC ED directors and institute collection of stool specimens. Three of four specimens collected were positive for norovirus. In December 2002, DOHMH investigated why an ED syndromic signal was not generated after 15 ill patients were transferred to a participating ED during a gastrointestinal outbreak at a nursing home. Field investigation revealed varying chief complaints, multiple dates of ED visits, and a coding error in a complementary DOHMH syndromic system, and confirmed a seasonal norovirus outbreak. During March 2003, the system generated a 4-day citywide respiratory signal and a simultaneous 1-day hospital-level fever signal in a predominantly Asian community. In those instances, epidemiologic investigation provided reassurance that severe acute respiratory syndrome was not present. CONCLUSION: Detailed field investigations of syndromic signals can identify the etiology of signals and determine why a given syndromic surveillance system failed to detect an outbreak captured through traditional surveillance. Validation of the utility of syndromic surveillance to detect infectious-disease outbreaks is necessary to justify allocating resources for this new public health tool.