Prevalence and predictors of cigarette smoking among people with HIV in Western Jamaica.

With highly active antiretroviral therapy, HIV infection has become a treatable chronic disease. However, modifiable risk factors such as cigarette smoking continue to impact the morbidity and mortality of people with HIV (PWH). We assessed the prevalence and factors associated with cigarette smoking and motivation to quit among PWH in Western Jamaica. A cross-sectional study was conducted in which 392 adults seeking HIV care at health facilities in Western Jamaica completed an interviewer-administered questionnaire. Current smoking prevalence among participants was 17.4%. Current smoking was significantly associated with being male (OR = 2.99), non-Christian/non-Rastafarian (OR = 2.34), living or working with another smoker (aOR =1.86), being moderate to severely depressed (OR = 3.24), having an alcohol drinking problem (OR = 1.84), and never being asked by a healthcare provider if they smoked (OR = 3.24). Among the PWH who currently smoke, 36.7% are moderately to highly dependent on nicotine. One-third of people who smoke (33.8%) started smoking for the first time after HIV diagnosis, while 66.2% initiated smoking before; 88% were willing to quit smoking. These findings provide baseline information for designing and implementing a comprehensive smoking cessation program that considers the needs of PWH in Jamaica, with the potential of becoming a replicable model for other HIV-specialized healthcare settings in the Caribbean.

Enhancing routine HIV and STI testing among young men who have sex with men: primary outcomes of the get connected clinical randomized trial (ATN 139).

BACKGROUND: Regular HIV and STI testing remain a cornerstone of comprehensive sexual health care. In this study, we examine the efficacy of Get Connected, a WebApp that combines test locators with personalized educational resources, in motivating young men who have sex with men (YMSM) to undergo regular HIV and STI testing. METHODS: Participants were randomly placed in one of two conditions. The first condition included the full version of GC (GC-PLUS), which included content tailored to users' psychosocial characteristics (e.g., age, race/ethnicity, relationship status, HIV/STI testing history). The second condition served as our attention-control and only included the testing locator (GC-TLO) for HIV/STI testing services. Participants were recruited from three cities (Houston, Philadelphia, and Atlanta) characterized by high HIV incidence. Assessments were collected at 1, 3-, 6-, 9- and 12-month follow-ups. RESULTS: Both versions of GC were acceptable and efficacious in increasing routine HIV and STI testing over a 12-month period. 40% of the sample reported testing at least twice, with no main effects observed across the two intervention arms (OR = 1.11; 95% CI: 0.69, 1.80), p =.66). Greater intervention effects were observed among YMSM who engaged more frequently with the intervention, with regional differences observed. CONCLUSIONS: Our findings underscore the need to cater to the diverse needs of YMSM through multilevel approaches. Broadly, mHealth HIV/STI testing interventions, such as Get Connected, would benefit from matching technologies to the local context to have the greatest impact. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT03132415).

A multidimensional tool to measure farm stressors: development and initial validation of the farmer stress assessment tool (FSAT).

BACKGROUND: Farming is a stressful occupation, and a growing body of research shows that farm stressors are associated with poor mental health. To date, there are few methodologically sound surveys that assess farm stressors, and none have been validated for the Canadian context. Our study aimed to: (a) investigate the types of stressors experienced by farmers, (b) develop a farm stress assessment tool and test its factor structure and internal consistency, and (c) assess its criterion-related validity to self-reported levels of anxiety, depression, burnout, and resilience among farmers. METHODS: We developed a 20-item survey based on a review of the literature, examining existing farm stress surveys, and consulting 10 farmers and agricultural industry experts. Then, a convenience sample of farmers living in Alberta, Canada (Sample 1, N = 354) completed a questionnaire containing the 20-item farm stress survey and four validated measures that assessed depression, anxiety, burnout, and resilience. Sample 1 was used to assess the factor structure using exploratory factor analysis (EFA), internal consistency, and criterion-validity of the survey. Next, a convenience sample of farmers living outside of Alberta (Sample 2, N = 138) was used to evaluate the factor structure of the survey using confirmatory factor analysis (CFA). RESULTS: The results of the EFA revealed five underlying dimensions of farm stressors: Unexpected work disruptions, Agricultural hazards, Farm and financial planning, Isolation, and Regulations and public pressure. The subscales accounted for 61.6% of the variance, and the internal consistency (Cronbach's alpha) ranged from 0.66 to.75. Subscale correlations were below 0.44, indicating evidence of discriminant validity. Correlations between the five subscales and the four mental health outcome variables supported the criterion-related validity of the survey. The results of the CFA indicated that the data fit the model, and fit was further improved by correlating one pair of error terms. CONCLUSIONS: Preliminary analysis of our Farmer Stress Assessment Tool (FSAT) suggests it is a reliable and valid instrument for measuring a range of stressors farmers face. Implications for policy and community-based mental health interventions that help farmers manage the enduring stressors of agriculture is discussed.

Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers.

INTRODUCTION: Microsatellite instability (MSI) testing and tumor mutational burden (TMB) are genomic biomarkers used to identify patients who are likely to benefit from immune checkpoint inhibitors. Pembrolizumab was recently approved by the Food and Drug Administration for use in TMB-high (TMB-H) tumors, regardless of histology, based on KEYNOTE-158. The primary objective of this retrospective study was real-world applicability and use of immunotherapy in TMB/MSI-high patients to lend credence to and refine this biomarker. METHODS: Charts of patients with advanced solid tumors who had MSI/TMB status determined by next generation sequencing (NGS) (FoundationOne CDx) were reviewed. Demographics, diagnosis, treatment history, and overall response rate (ORR) were abstracted. Progression-free survival (PFS) was determined from Kaplan-Meier curves. PFS1 (chemotherapy PFS) and PFS2 (immunotherapy PFS) were determined for patients who received immunotherapy after progressing on chemotherapy. The median PFS2/PFS1 ratio was recorded. RESULTS: MSI-high or TMB-H [≥20 mutations per megabase (mut/MB)] was detected in 157 adults with a total of 27 distinct tumor histologies. Median turnaround time for NGS was 73 days. ORR for most recent chemotherapy was 34.4%. ORR for immunotherapy was 55.9%. Median PFS for patients who received chemotherapy versus immunotherapy was 6.75 months (95% confidence interval, 3.9-10.9 months) and 24.2 months (95% confidence interval, 9.6 months to not reached), respectively (P = 0.042). Median PFS2/PFS1 ratio was 4.7 in favor of immunotherapy. CONCLUSION: This real-world study reinforces the use of TMB as a predictive biomarker. Barriers exist to the timely implementation of NGS-based biomarkers and more data are needed to raise awareness about the clinical utility of TMB. Clinicians should consider treating TMB-H patients with immunotherapy regardless of their histology.

Knowledge, attitudes and behaviours associated with the provision of hepatitis C care by Canadian family physicians.

The role of primary care physicians in providing care for hepatitis C virus (HCV) infection is increasingly emphasized, but many gaps and challenges remain. This study explores family physicians' knowledge, attitudes and practices associated with providing care for HCV infection. Seven hundred and forty-nine members of the College of Family Physicians of Canada (CFPC) completed a self-administered survey examining knowledge, attitudes and behaviours regarding HCV infection screening and care. Multivariate analyses were performed using the outcome, HCV care provision, and variables based on a conceptual model of practice guideline adherence. Family physicians providing basic-advanced HCV care were more likely to be older, practice in a rural setting, have injection drug users (IDU) in their practice and have higher levels of knowledge about the initial assessment (OR = 1.77; 95% CI = 1.23-2.54) and treatment of HCV (OR = 1.74; 95% CI = 1.24-2.43). They were also less likely to believe that family physicians do not have a role in HCV care (OR = 0.41; 95% CI = 0.30-0.58). Educational programmes should target physicians less likely to provide HCV care, namely family physicians practicing in urban areas and those who do not care for any IDU patients. Training and continuing medical education programmes that aim to shift family physicians' attitudes about the provision of HCV care by promoting their roles as integral to HCV care could contribute to easing the burden on consultant physicians and lead to improved access to treatment for HCV infection.

Bioavailability of xenobiotics in the soil environment.

It is often presumed that all chemicals in soil are available to microorganisms, plant roots, and soil fauna via dermal exposure. Subsequent bioaccumulation through the food chain may then result in exposure to higher organisms. Using the presumption of total availability, national governments reduce environmental threshold levels of regulated chemicals by increasing guideline safety margins. However, evidence shows that chemical residues in the soil environment are not always bioavailable. Hence, actual chemical exposure levels of biota are much less than concentrations present in soil would suggest. Because "bioavailability" conveys meaning that combines implications of chemical sol persistency, efficacy, and toxicity, insights on the magnitude of a chemicals soil bioavailability is valuable. however, soil bioavailability of chemicals is a complex topic, and is affected by chemical properties, soil properties, species exposed, climate, and interaction processes. In this review, the state-of-art scientific basis for bioavailability is addressed. Key points covered include: definition, factors affecting bioavailability, equations governing key transport and distributive kinetics, and primary methods for estimating bioavailability. Primary transport mechanisms in living organisms, critical to an understanding of bioavailability, also presage the review. Transport of lipophilic chemicals occurs mainly by passive diffusion for all microorganisms, plants, and soil fauna. Therefore, the distribution of a chemical between organisms and soil (bioavailable proportion) follows partition equilibrium theory. However, a chemical's bioavailability does not always follow partition equilibrium theory because of other interactions with soil, such as soil sorption, hysteretic desorption, effects of surfactants in pore water, formation of "bound residue", etc. Bioassays for estimating chemical bioavailability have been introduced with several targeted endpoints: microbial degradation, uptake by higher plants and soil fauna, and toxicity to organisms. However, there bioassays are often time consuming and laborious. Thus, mild extraction methods have been employed to estimate bioavailability of chemicals. Mild methods include sequential extraction using alcohols, hexane/water, supercritical fluids (carbon dioxide), aqueous hydroxypropyl-beta-cyclodextrin extraction, polymeric TENAX beads extraction, and poly(dimethylsiloxane)-coated solid-phase microextraction. It should be noted that mild extraction methods may predict bioavailability at the moment when measurements are carried out, but not the changes in bioavailability that may occur over time. Simulation models are needed to estimate better bioavailability as a function of exposure time. In the past, models have progressed significantly by addressing each group of organisms separately: microbial degradation, plant uptake via evapotranspiration processes, and uptake of soil fauna in their habitat. This approach has been used primarily because of wide differences in the physiology and behaviors of such disparate organisms. However, improvement of models is badly needed, Particularly to describe uptake processes by plant and animals that impinge on bioavailability. Although models are required to describe all important factors that may affect chemical bioavailability to individual organisms over time (e.g., sorption/desorption to soil/sediment, volatilization, dissolution, aging, "bound residue" formation, biodegradation, etc.), these models should be simplified, when possible, to limit the number of parameters to the practical minimum. Although significant scientific progress has been made in understanding the complexities in specific methodologies dedicated to determining bioavailability, no method has yet emerged to characterized bioavailability across a wide range of chemicals, organisms, and soils/sediments. The primary aim in studying bioavailability is to define options for addressing bioremediation or environmental toxicity (risk assessment), and that is unlikely to change. Because of its importance in estimating research is needed to more comprehensively address the key environmental issue of "bioavailability of chemicals in soil/sediment."

Wheat and sorghum residue removal for expanded uses increases sediment and nutrient loss in runoff.

Crop residue removal for expanded uses such as feedstocks for cellulosic ethanol production may increase loss of sediment and nutrients in runoff. We assessed on-farm impacts of variable rates of residue removal from no-till winter wheat (Triticum aestivum L.) and plow till grain sorghum [Sorghum bicolor (L.) Moench] on sediment, soil organic carbon (SOC) and nutrient losses in runoff in western Kansas. Five treatments with three replications consisting of removing residues at 0, 25, 50, 75, and 100% after harvest under two tillage levels for wheat (no-till and freshly tilled) and grain sorghum (spring tilled and freshly tilled) were established on 1x2 m plots. Simulated rainfall was applied at 115+/-3 mm h(-1) for 30 min. Compared with plots without residue removal, complete removal increased runoff by 61% in freshly tilled wheat plots, 225% in spring-tilled sorghum plots, and 94% in freshly tilled sorghum plots. Residue removal at rates as low as 50% increased loss of sediment. Complete removal doubled the sediment loss to 14 Mg ha(-1) in tilled wheat, whereas it increased sediment loss from 0.9 to 7.2 Mg ha(-1) in no-till wheat. No-till with 100% residue removal lost as much sediment as freshly tilled wheat plots with 0 or 25% removal. Residue removal at 75 and 100% increased losses of total N, total P, and SOC associated with sediment. Overall, excessive residue removal led to large losses of sediment, sediment-bound SOC, and nutrients in runoff. Furthermore, erosion protection provided by no-till management is lost when residue removal exceeds 25%.

Concordance in the reporting of intimate partner violence among male-male couples.

Intimate partner violence (IPV) among male couples is increasingly recognized as a public health concern. Research on IPV in opposite sex couples indicates frequent underreporting of IPV and high levels of discordance in reporting among dyads. Concordance studies inform refinement methods to measure the experience of IPV among dyads; however the lack of dyadic studies of male couples impedes our understanding of the extent to which IPV is differentially reported in male-male dyads. This study utilized baseline data from a randomized controlled trial of a behavioral intervention to optimize antiretroviral therapy (ART) adherence among 160 sero-discordant male couples in three US cities and provides the first analysis of concordance in reporting IPV among male couples. Low degrees of concordance in the reporting of IPV were identified among male dyads, with a greater proportion of men reporting violence perpetration than experiencing violence. The greater reporting of IPV perpetration may be linked to adherence to concepts of masculinity. The results underscore the unique experiences of IPV among male couples and the need to reexamine current IPV measurement and intervention strategies.

The demographic profile of sero-discordant couples enrolled in clinical research in Rwanda and Zambia.

This paper examines the demographic profile of two cohorts of sero-discordant couples enrolled in research activities at two clinical research sites in Kigali, Rwanda and Lusaka, Zambia and compares their background characteristics by country, gender and sero-status. Differences between the two cohorts represent economic and cultural differences between the two countries. Recruitment procedures appear to be successful in reaching the intended audience - couples from poor urban communities - and we suggest that similar recruitment strategies could be adopted to reach other population groups in other settings. The profiles of sero-discordant couples highlight several potential intervention points, and call for attention to be focused towards prevention efforts aimed at young women and their male partners.

The impact of project closure on HIV incidence and mortality in a cohort of couples in Lusaka, Zambia.

The objective of this study was to assess the impact of temporary closure of an HIV research clinic on the health of study participants. Primary data were collected quarterly from couples enrolled in research studies at an established HIV study site. There were 632 participating couples enrolled when the project closed, 475 of whom returned when it re-opened six months later. HIV sero-incidence, mortality rates and risk-taking behaviours were compared before and during the closure. Perceived impact of the closure was measured in returning participants. Demographic data collected at the last pre-closure study visit were used to look at the differences between returning and non-returning study participants. Serologic data from those who returned were compared pre- and post-closure to examine changes in HIV incidence. Mortality rates were estimated from reported deaths, and were compared pre- and during project closure. Perceptions of the impact of the closure among returning participants were examined through an interviewer administered questionnaire. It was found that couples who returned were not demographically different from couples who did not return. Most participants reported no problems with finding alternate sources of condoms and the incidence of HIV did not change significantly during the closure. Eighty-four percent respondents reported that the closure had a negative impact on them, 87% of whom rated loss of medical care as the main impact. The mortality rate among HIV-positive participants doubled from 6.7/100 person years to 12.4/100 person years during the closure (p=0.01). Results indicate that couples voluntary counselling and testing (CVCT) established durable risk-reduction behaviours that persisted during project closure. ThIn ae loss of healthcare was perceived as the most negative impact on participants, reflected in increased mortality rates. Research projects should make transition plans and budget for mechanisms to reduce the negative impact on participants of project closures.

Isometric Finger Pose Recognition with Sparse Channel SpatioTemporal EMG Imaging.

High fidelity myoelectric control of prostheses and orthoses isparamount to restoring lost function to amputees and neuro-muscular disease sufferers. In this study we prove that patio-temporal imaging can be used to allow convolutional neural networks to classify sparse channel EMG samples from a consumer-grade device with over 94 % accuracy. 10,572 images are generated from 960 samples of simple and complex isometric finger poses recorded from 4 fully intact subjects. Real-time classification of 12 poses is achieved with a 250ms continuous overlapping window.

Swimming Against the Current: A Qualitative Review of the Work Experiences and Adaptations Made by Employees With Arthritis.

OBJECTIVE: To describe the experiences and strategies of employees with arthritis to maintain employment, and to use this information to build a conceptual model. METHODS: We conducted a systematic review of qualitative studies that examined the work experiences of employees with arthritis. Published studies on arthritis and employment were searched from electronic databases (1980-2017) and bibliographic reviews of relevant studies. We used meta-ethnography to synthesize the findings. RESULTS: We reviewed 17 studies that reported on the experiences of 873 employees. We identified 11 main themes that highlight common issues experienced by employees with arthritis and grouped these into 4 higher-order categories: changing nature of the disease (emotional issues, cognitive struggles, unpredictable physical symptoms), intrapersonal issues (personal meaning of work, preserving a work identity), interpersonal issues (managing disclosure, gaining coworker support, organizational culture issues), and work-sustainability strategies (making personal adjustments, using social support, using workplace accommodations). Using these themes, we developed the Job Sustainability Model to illustrate how disease, personal, and work-related factors interact to influence what type of coping behaviors are used and when. Initially, employees with arthritis rely on making personal adjustments, using social support, and medical intervention. However, when these coping behaviors fail to be effective, they draw upon workplace accommodations and resources. CONCLUSION: Arthritis disrupts an employee's work life by impairing his or her capacity to be a productive worker. Our results highlight how employees with arthritis make strategic adaptations to maintain a productive work life for as long as possible. The findings of this study have implications for work-related interventions aimed at preserving employment.

Mammalian SWI-SNF complexes contribute to activation of the hsp70 gene.

ATP-dependent chromatin-remodeling complexes are conserved among all eukaryotes and function by altering nucleosome structure to allow cellular regulatory factors access to the DNA. Mammalian SWI-SNF complexes contain either of two highly conserved ATPase subunits: BRG1 or BRM. To identify cellular genes that require mammalian SWI-SNF complexes for the activation of gene expression, we have generated cell lines that inducibly express mutant forms of the BRG1 or BRM ATPases that are unable to bind and hydrolyze ATP. The mutant subunits physically associate with at least two endogenous members of mammalian SWI-SNF complexes, suggesting that nonfunctional, dominant negative complexes may be formed. We determined that expression of the mutant BRG1 or BRM proteins impaired the ability of cells to activate the endogenous stress response gene hsp70 in response to arsenite, a metabolic inhibitor, or cadmium, a heavy metal. Activation of hsp70 by heat stress, however, was unaffected. Activation of the heme oxygenase 1 promoter by arsenite or cadmium and activation of the cadmium-inducible metallothionein promoter also were unaffected by the expression of mutant SWI-SNF components. Analysis of a subset of constitutively expressed genes revealed no or minimal effects on transcript levels. We propose that the requirement for mammalian SWI-SNF complexes in gene activation events will be specific to individual genes and signaling pathways.

Inhibition of mouse natural killer cell activity by zinc.

The effect of zinc on mouse natural killer (NK) cell activity was evaluated. The inhibition of NK cell activity with zinc was dependent on the concentration of zinc added (range tested: 0-40 micrograms zinc/ml) and occurred at both effector-to-target ratios tested. Zinc-induced inhibition of NK activity was observed with the use of peritoneal or splenic effector cells on Toxoplasma gondii-augmented NK activity. Maximal inhibition of activity was noted when zinc was present for the entire assay period. Inhibition was present but less marked with pretreatment of effector cells with zinc. Pretreatment of target cells with zinc had no measurable effect on NK cytotoxicity. Effector-to-target cell binding as measured by single-cell assays was not significantly altered by zinc. These results indicate that zinc is a potent inhibitor of NK activity.

Metastatic model for human prostate cancer using orthotopic implantation in nude mice.

BACKGROUND: Understanding the mechanism of prostate cancer metastasis is essential to the design of a more effective therapy. An effective therapy for this disease will depend on the development of a clinically relevant in vivo model. PURPOSE: We describe the development of such a model by using orthotopic implantation of human prostate cells in BALB/c nude mice. METHOD: We compared the tumorigenicity of and the incidence of metastasis of human prostate cancer PC-3M and LNCaP-FGC (LNCaP) cell lines subsequent to prostatic (orthotopic) or subcutaneous (ectopic) implantations in male nude mice. RESULTS: LNCaP cells produced tumors only in the prostate. Enhanced tumorigenicity at the orthotopic site was found for PC-3M cells. Lymph node metastases were observed in practically all mice given an injection of PC-3M cells in the prostate, but they were uncommon with subcutaneous injection of these cells. Bilateral orchiectomy did not alter the tumorigenicity of either PC-3M or LNCaP cells or the incidence of lymph node metastasis by PC-3M cells. LNCaP tumors in the mouse prostate (but not PC-3M tumors) elaborated detectable levels of human prostate-specific antigen (PSA) in the serum, even when tumors were small (1.5 mm in diameter). Immunohistochemistry analysis revealed the presence of the PSA marker in tissue sections of LNCaP but not of PC-3M tumors. CONCLUSIONS: The implantation of human prostate cancer cells in an ectopic environment does not permit expression of metastatic potential. In contrast, intraprostatic implantation does. IMPLICATIONS: These data suggest that the orthotopic injection of human prostate cancer cells into the nude mouse may provide a valuable model to study the biology and therapy of human prostate cancer.

Factors associated with initial therapy for clinically localized prostate cancer: prostate cancer outcomes study.

BACKGROUND: Because of the lack of results from randomized clinical trials comparing the efficacy of aggressive therapies with that of more conservative therapies for clinically localized prostate cancer, men and their physicians may select treatments based on other criteria. We examined the association of sociodemographic and clinical characteristics with four management options: radical prostatectomy, radiation therapy, hormonal therapy, and watchful waiting. METHODS: We studied 3073 participants of the Prostate Cancer Outcomes Study diagnosed from October 1, 1994, through October 31, 1995, with clinically localized disease (T1 or T2). Participants completed a baseline survey, and diagnostic and treatment information was abstracted from medical records. Multiple logistic regression analysis identified factors associated with initial treatment. All statistical tests were two-sided. RESULTS: Patients with clinically localized disease received the following treatments: radical prostatectomy (47.6%), radiation therapy (23.4%), hormonal therapy (10.5%), or watchful waiting (18.5%). Men aged 75 years or older more often received conservative treatment (i.e., hormonal therapy alone or watchful waiting; 57.9% of men aged 75-79 years and 82.1% of men aged 80 years and older) than aggressive treatment (i.e., radical prostatectomy or radiation therapy) (for all age groups, P

Health outcomes after prostatectomy or radiotherapy for prostate cancer: results from the Prostate Cancer Outcomes Study.

BACKGROUND: Radical prostatectomy and external beam radiotherapy are the two major therapeutic options for treating clinically localized prostate cancer. Because survival is often favorable regardless of therapy, treatment decisions may depend on other therapy-specific health outcomes. In this study, we compared the effects of two treatments on urinary, bowel, and sexual functions and on general health-related quality-of-life outcomes over a 2-year period following initial treatment. METHODS: A diverse cohort of patients aged 55-74 years who were newly diagnosed with clinically localized prostate cancer and received either radical prostatectomy (n = 1156) or external beam radiotherapy (n = 435) were included in this study. A propensity score was used to balance the two treatment groups because they differed in some baseline characteristics. This score was used in multivariable cross-sectional and longitudinal regression analyses comparing the treatment groups. All statistical tests were two-sided. RESULTS: Almost 2 years after treatment, men receiving radical prostatectomy were more likely than men receiving radiotherapy to be incontinent (9.6% versus 3.5%; P:<.001) and to have higher rates of impotence (79.6% versus 61.5%; P:<.001), although large, statistically significant declines in sexual function were observed in both treatment groups. In contrast, men receiving radiotherapy reported greater declines in bowel function than did men receiving radical prostatectomy. All of these differences remained after adjustments for propensity score. The treatment groups were similar in terms of general health-related quality of life. CONCLUSIONS: There are important differences in urinary, bowel, and sexual functions over 2 years after different treatments for clinically localized prostate cancer. In contrast to previous reports, these outcome differences reflect treatment delivered to a heterogeneous group of patients in diverse health care settings. These results provide comprehensive and representative information about long-term treatment complications to help guide and inform patients and clinicians about prostate cancer treatment decisions.

Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study.

BACKGROUND: African-Americans have twice the risk of non-Hispanic whites for presenting with advanced-stage prostate cancer. To investigate the reasons for this difference, we evaluated the association between race/ethnicity and advanced-stage prostate cancer, adjusting for demographic, socioeconomic, clinical, and pathologic factors. METHODS: A population-based cohort of 3173 men diagnosed with prostate cancer between October 1, 1994, and October 31, 1995, was analyzed. Medical record abstracts and self-administered survey questionnaires were used to obtain information regarding race/ethnicity, age, marital status, insurance status, educational level, household income, employment status, comorbidity, urinary function, prostate-specific antigen level, tumor grade, and clinical stage. The odds ratio (OR) for advanced-stage prostate cancer was estimated with weighted logistic regression analysis. All P: values were two-sided. RESULTS: Clinically advanced-stage prostate cancers were detected more frequently in African-Americans (12.3%) and Hispanics (10.5%) than in non-Hispanic whites (6.3%). Socioeconomic, clinical, and pathologic factors each accounted for about 15% of the increased relative risk. After adjusting for all covariates, the risk remained statistically significantly increased for African-Americans (OR = 2.26; 95% confidence interval [CI] = 1.43 to 3.58) but not for Hispanics (OR = 1.23; 95% CI = 0.73 to 2.08). CONCLUSION: Traditional socioeconomic, clinical, and pathologic factors accounted for the increased relative risk for presenting with advanced-stage prostate cancer in Hispanic but not in African-American men.

Flow cytometry of prostate cancer: relationship of DNA content to survival.

Between March 1970 and December 1978 there were 366 patients with prostatic cancer treated by 125I seed implants and pelvic lymph node dissection. All had a minimum of 5 years follow-up. One hundred thirty-three patients had metastatic prostatic cancer in lymph nodes (Stage D1) at the time of lymph node dissection and seed implantation. Ninety-one of the 133 patients were judged to have sufficient metastatic prostatic cancer in their nodal tissue (greater than 50% replacement with tumor) to justify flow cytometric cellular DNA measurements on the involved paraffin-embedded nodal tissue. Nine patients were excluded due to uninterpretable DNA histograms leaving 82 patients for analysis. Forty-nine patients had aneuploid and 33 had diploid tumors. There was no statistical bias between the aneuploid and diploid groups due to age (P = 0.970, chi 2 test), time between diagnosis and implantation (P = 0.217, chi 2 test), number of positive nodes (P = 0.669, two-sample t test of means), or tumor grade (P = 0.332, chi 2 test). Median survival time of the aneuploid and diploid groups was 5.0 and 8.8 years, respectively (P = 0.0109, log rank test). Cox regression analysis confirmed the effect of aneuploidy versus diploidy on survival by controlling for other potentially confounding variables (age, time from diagnosis to implantation, number of positive nodes, and grade). Grade as a predictor of survival did not approach statistical significance in this series of relatively small size (P = 0.116). Thirty-eight of the 82 patients had moderately differentiated neoplasms. Nineteen of these were aneuploid and 19 diploid. The median survival was 5.8 and 9.1 years, respectively, for these grade-matched aneuploid and diploid groups (P = 0.039, log rank test). We conclude that flow cytometric DNA measurements on archived paraffin-embedded tumor in nodal metastases appear to be a strong predictor of survival for Stage DI prostatic cancer.

Inhibition of potato starch phosphorylase by alpha-D-glucopyranose-1,2-cyclic phosphate.

alpha-D-Glucopyranose-1.2-cyclic phosphate is a potent inhibitor of potato starch phosphorylase-catalyzed (1,4-alpha-D-glucan:orthophosphate alpha-glucosyltransferase, EC 2.4.1.1) starch elongation. The inhibition is competitive with respect to alpha-D-glucopyranose 1-phosphate (Glc-1-P) with Ki approximately 0.07 mM at pH 6.3 and 30 degrees C in 25 mM citrate buffer. The affinity of the phosphorylase - starch complex for the cyclic ester is therefore nearly 30 times as large as for Glc-1-P. Under conditions where alpha-D-glucopyranose-1,2-cyclic phosphate slows starch elongation by a factor of 3, UDPglucose, ADPglucose, D-glucose 6-phosphate, and D-glucose 2-phosphate cause rate reductions of less than 10%. The origin of the relatively strong binding of the cyclic ester to the phosphorylase, and its possible biological significance are discussed.