Biosynthesis and characterization of fuscimiditide, an aspartimidylated graspetide.

Microviridins and other ω-ester-linked peptides, collectively known as graspetides, are characterized by side-chain-side-chain linkages installed by ATP-grasp enzymes. Here we report the discovery of a family of graspetides, the gene clusters of which also encode an O-methyltransferase with homology to the protein repair catalyst protein L-isoaspartyl methyltransferase. Using heterologous expression, we produced fuscimiditide, a ribosomally synthesized and post-translationally modified peptide (RiPP). NMR analysis of fuscimiditide revealed that the peptide contains two ester cross-links forming a stem-loop macrocycle. Furthermore, an unusually stable aspartimide moiety is found within the loop macrocycle. We fully reconstituted fuscimiditide biosynthesis in vitro including formation of the ester and aspartimide moieties. The aspartimide moiety embedded in fuscimiditide hydrolyses regioselectively to isoaspartate. Surprisingly, this isoaspartate-containing peptide is also a substrate for the L-isoaspartyl methyltransferase homologue, thus driving any hydrolysis products back to the aspartimide form. Whereas an aspartimide is often considered a nuisance product in protein formulations, our data suggest that some RiPPs have aspartimide residues intentionally installed via enzymatic activity.

Integrating cervical cancer screening and preventive treatment with family planning and HIV-related services.

Cervical cancer is a leading cause of mortality in Sub-Saharan Africa-in large part because of inadequate coverage of screening and preventive treatment services. A number of programs have begun integrating cervical cancer prevention services into existing family planning or HIV/AIDS service delivery platforms, to rapidly expand "screen and treat" programs and mitigate cervical cancer burden. Drawing upon a review of literature and our experiences, we consider benefits and challenges associated with such programs in Sub-Saharan Africa. We then outline steps that can optimize uptake and sustainability of integrated sexual and reproductive health services. These include increasing coordination among implementing organizations for efficient use of resources; task shifting for services that can be provided by nonphysicians; mobilizing communities via trusted frontline health workers; strengthening management information systems to allow for monitoring of multiple services; and prioritizing an operational research agenda to provide further evidence on the cost-effectiveness and benefits of integrated service delivery.

Modeling the cumulative effects of social exposures on health: moving beyond disease-specific models.

The traditional explanatory models used in epidemiology are "disease specific", identifying risk factors for specific health conditions. Yet social exposures lead to a generalized, cumulative health impact which may not be specific to one illness. Disease-specific models may therefore misestimate social factors' effects on health. Using data from the Canadian Community Health Survey and Canada 2001 Census we construct and compare "disease-specific" and "generalized health impact" (GHI) models to gauge the negative health effects of one social exposure: socioeconomic position (SEP). We use logistic and multinomial multilevel modeling with neighbourhood-level material deprivation, individual-level education and household income to compare and contrast the two approaches. In disease-specific models, the social determinants under study were each associated with the health conditions of interest. However, larger effect sizes were apparent when outcomes were modeled as compound health problems (0, 1, 2, or 3+ conditions) using the GHI approach. To more accurately estimate social exposures' impacts on population health, researchers should consider a GHI framework.

Defining hospitalist physicians using clinical practice data: a systems-level pilot study of Ontario physicians.

BACKGROUND: Hospitalists have become dominant providers of inpatient care in many North American hospitals. Despite the global growth of hospital medicine, no objective method has been proposed for defining the hospitalist discipline and delineating among inpatient practices on the basis of physicians' clinical volumes. We propose a functional method of identifying hospital-based physicians using aggregated measures of inpatient volume and apply this method to a retrospective, population-based cohort to describe the growth of the hospitalist movement, as well as the prevalence and practice characteristics of hospital-based generalists in one Canadian province. METHODS: We used human resource databases and financial insurance claims to identify all active fee-for-service physicians working in Ontario, Canada, between fiscal year 1996/1997 and fiscal year 2010/2011. We constructed 3 measures of inpatient volume from the insurance claims to reflect the time that physicians spent delivering inpatient care in each fiscal year. We then examined how inpatient volumes have changed for Ontario physicians over time and described the prevalence of full-time and part-time hospital-based generalists working in acute care hospitals in fiscal year 2010/2011. RESULTS: Our analyses showed a significant increase since fiscal year 2000/2001 in the number of high-volume hospital-based family physicians practising in Ontario (p < 0.001) and associated decreases in the numbers of high-volume internists and specialists (p = 0.03), where high volume was defined as ≥ 2000 inpatient services/ year. We estimated that 620 full-time and 520 part-time hospital-based physicians were working in Ontario hospitals in 2010/2011, accounting for 4.5% of the active physician workforce (n = 25 434). Hospital-based generalists, consisting of 207 family physicians and 130 general internists, were prevalent in all geographic regions and hospital types and collectively delivered 10% of all inpatient evaluation and care coordination for Ontario residents who had been admitted to hospital. INTERPRETATION: These analyses confirmed a substantial increase in the prevalence of general hospitalists in Ontario from 1996 to 2011. Systems-level analyses of clinical practice data represent a practical and valid method for defining and identifying hospital-based physicians.

'Worse than HIV' or 'not as serious as other diseases'? Conceptualization of cervical cancer among newly screened women in Zambia.

Invasive cervical cancer is the second most common cancer among women worldwide, with approximately 85% of the disease burden occurring in developing countries. To date, there have been few systematic efforts to document African women's conceptualization of cervical cancer after participation in a visual inspection with acetic acid (VIA)-based "see and treat" cervical cancer prevention program. In this study, conducted between September, 2009-July, 2010, focus groups and in-depth interviews were conducted with 60 women who had recently undergone cervical cancer screening at a government-operated primary health care clinic in Lusaka, Zambia. Interviewers elicited participants' causal representations of cervical cancer, associated physical signs and symptoms, perceived physical and psychological effects, and social norms regarding the disease. The lay model of illness causation portrayed by participants after recent exposure to program promotion messages departed in several ways from causal models described in other parts of the world. However, causal conceptualizations included both lay and biomedical elements, suggesting a possible shift from a purely traditional causal model to one that incorporates both traditional concepts and recently promoted biomedical concepts. Most, but not all, women still equated cervical cancer with death, and perceived it to be a highly stigmatized disease in Zambia because of its anatomic location, dire natural course, connections to socially-condemned behaviors, and association with HIV/AIDS. No substantive differences of disease conceptualization existed according to HIV serostatus, though HIV positive women acknowledged that their immune status makes them more aware of their health and more likely to seek medical attention. Further attention should be dedicated to the processes by which women incorporate new knowledge into their representations of cervical cancer.

Motivations and experiences of women who accessed "see and treat" cervical cancer prevention services in Zambia.

BACKGROUND: In Zambia, a country with a generalized HIV epidemic, age-adjusted cervical cancer incidence is among the highest worldwide. In 2006, the University of Alabama at Birmingham-Center for Infectious Disease Research in Zambia and the Zambian Ministry of Health launched a visual inspection with acetic acid (VIA) -based "see and treat" cervical cancer prevention program in Lusaka. All services were integrated within existing government-operated primary health care facilities. OBJECTIVE: Study aims were to (i) identify women's motivations for cervical screening, (ii) document women's experiences with screening and (iii) describe the potentially reciprocal influences between women undergoing cervical screening and their social networks. DESIGN AND METHODS: Focus group discussions (FGD) and in-depth interviews (IDI) were conducted with women who accepted screening and with care providers. Low-level content analysis was performed to identify themes evoked by participants. Between September 2009 and July 2010, 60 women and 21 care providers participated in 8 FGD and 10 IDI. RESULTS: Women presented for screening with varying needs and expectations. A majority discussed their screening decisions and experiences with members of their social networks. Key reinforcing factors and obstacles to VIA screening were identified. CONCLUSIONS: Interventions are needed to gain support for the screening process from influential family members and peers.

Drinking in context: the influence of gender and neighbourhood deprivation on alcohol consumption.

BACKGROUND: Findings from contextual studies have shown that living in both poor and affluent neighbourhoods increases the risk of drinking and drug use, but few studies have examined the connection between neighbourhood context and drinking from a gender perspective. METHODS: We investigated the association between gender, neighbourhood deprivation and weekly drinking behaviour (number of drinks) in a national sample of 93 457 Canadians using multilevel zero-inflated Poisson regression. A cross-level interaction between gender and neighbourhood deprivation was examined while controlling for other potential risk factors. RESULTS: 53% of Canadians reported having at least one drink in the last year (men=61%; women=46%). Among respondents who were drinkers, the average number of drinks per week was 6.4 with male drinkers reporting an average of 7.9 and female drinkers reporting an average of 4.6. Neighbourhood material deprivation was independently associated with weekly drinking. Findings from multilevel analysis showed a u-shaped curve between neighbourhood deprivation and drinking, but only for men. Men living in the poorest neighbourhoods drank more weekly (8.5 drinks) than men living in neighbourhoods of wealthy (4.5 drinks) and mid-range deprivation (3.7 drinks). No difference in drinking by neighbourhood material deprivation was observed among women. CONCLUSION: Men, like women, experience gender-specific health difficulties (eg, alcohol-related problems) suggesting the need for a gendered focus on policies and services related to women's and men's health. The challenge for public health and primary care is to work together to target risk-taking behaviours among men through treatment, prevention and cultural/educational messages aimed at building healthy lifestyles.

Capturing paediatric injury in Ontario: differences in injury incidence using self-reported survey and health service utilisation data.

OBJECTIVE: Population-based health surveys are increasingly popular sources of data on injury occurrence. Self-reported surveys can yield estimates of the total incidence of non-fatal injuries while simultaneously capturing a rich repository of contextual data that may be informative for exploring determinants of injury risk. Although survey data are rarely recognised as complete, several researchers have expressed concerns about the sensitivity and validity of self-reported injury data, questioning whether captured cases are representative of the population experience of injury, particularly among children and youth. The present study sought to compare the population incidence of paediatric injury estimated from self-reported survey responses to those documented by a complete-capture health service utilisation database among Ontario children. METHODS: Injury incidence rates documented from the National Longitudinal Survey of Children and Youth and the National Population Health Survey were compared with those reported in Canada's National Ambulatory Care Reporting System for Ontario youth aged 0-19 years for fiscal year 2002/3, stratified by the child's age and geographical location of residence. RESULTS: The two self-reported health surveys underestimated the population incidence of injury among Ontario children by at least 49% and 53%, respectively. Systematic errors exist in survey data capture such that injuries in infants and preschoolers (<4 years of age) and urban residents were most likely to be missed by the population health surveys. CONCLUSION: Injury incidence estimated through self-report is not representative of the population burden and experience of paediatric injury for Ontario children, and may produce biased estimates of risk when analysed as independent sources of data.

Do hospitalist physicians improve the quality of inpatient care delivery? A systematic review of process, efficiency and outcome measures.

BACKGROUND: Despite more than a decade of research on hospitalists and their performance, disagreement still exists regarding whether and how hospital-based physicians improve the quality of inpatient care delivery. This systematic review summarizes the findings from 65 comparative evaluations to determine whether hospitalists provide a higher quality of inpatient care relative to traditional inpatient physicians who maintain hospital privileges with concurrent outpatient practices. METHODS: Articles on hospitalist performance published between January 1996 and December 2010 were identified through MEDLINE, Embase, Science Citation Index, CINAHL, NHS Economic Evaluation Database and a hand-search of reference lists, key journals and editorials. Comparative evaluations presenting original, quantitative data on processes, efficiency or clinical outcome measures of care between hospitalists, community-based physicians and traditional academic attending physicians were included (n = 65). After proposing a conceptual framework for evaluating inpatient physician performance, major findings on quality are summarized according to their percentage change, direction and statistical significance. RESULTS: The majority of reviewed articles demonstrated that hospitalists are efficient providers of inpatient care on the basis of reductions in their patients' average length of stay (69%) and total hospital costs (70%); however, the clinical quality of hospitalist care appears to be comparable to that provided by their colleagues. The methodological quality of hospitalist evaluations remains a concern and has not improved over time. Persistent issues include insufficient reporting of source or sample populations (n = 30), patients lost to follow-up (n = 42) and estimates of effect or random variability (n = 35); inappropriate use of statistical tests (n = 55); and failure to adjust for established confounders (n = 37). CONCLUSIONS: Future research should include an expanded focus on the specific structures of care that differentiate hospitalists from other inpatient physician groups as well as the development of better conceptual and statistical models that identify and measure underlying mechanisms driving provider-outcome associations in quality.

Imaging diagnosis-heterobilharzia americana infection in a dog.

An approximately three-year-old mixed breed female dog was evaluated for peritoneal effusion, anorexia, intermittent vomiting, and diarrhea. Radiographically, there was mineralization of the wall of small intestinal segments. Sonographic findings were consistent with multisystemic mineralization of liver, small intestinal wall, and pancreas. Multifocal granulomas containing schistosome eggs (Heterobilharzia americana) were identified histologically. The mineralization pattern described herein is an uncommon presentation of severe diffuse heterobilharziasis in a dog.

A retrospective review of TATRC funding for medical modeling and simulation technologies.

INTRODUCTION: In February 2000, the U.S. Army's Telemedicine and Advanced Technology Research Center (TATRC) and the U.S. Army's Simulation, Training, and Instrumentation Command cohosted an Integrated Research Team conference in Maryland. The goal of the conference was to enable end users, researchers, materiel developers, and other government agencies to present their conceptions of how modeling and simulation could and should be developed to meet military medical needs. During the past 9 years, TATRC has funded more than 175 projects relating to simulation. METHODS: This study was a retrospective review of TATRC's Modeling and Simulation Training projects (N = 175). RESULTS: Our results show that most (>75%) of the funded projects in this study involved industry. More than 85% of the projects that involved industry focused on technology development. Industry development projects seemed to meet their deliverables in a timely fashion. However, academia projects using industry-developed technologies and prototypes were delayed largely because the technologies did not meet their needs. DISCUSSION: There seems to be a measurable gap between industry's definition of a completed product technology and academia's ability to implement and use the technology in interactive learning environments. Our findings support the need for a standardized strategic design process that involves a strong industry-academia collaboration and early end-user testing to better facilitate the development of sound requirements that guide technology development.

Influence of neighborhood deprivation, gender and ethno-racial origin on smoking behavior of Canadian youth.

OBJECTIVE: Deprived neighborhoods play an important role in adult smoking behavior, but little research exists about youth on this topic. This study explored the relationship between deprivation and youth smoking to examine whether this association differs by gender and ethno-racial origin. METHODS: Individual-level data from the Canadian Community Health Survey (2000-2005) were combined with neighborhood-level data from the 2001 Canada Census to assess smoking among youth aged 12-18 (n = 15,615). RESULTS: Youth who were female (OR = 1.27, 95%CI:1.16-1.38), White (OR = 1.95, 95%CI:1.71-2.21) and living in deprived neighborhoods (OR = 1.22, 95%CI:1.16-1.28) were more likely to smoke. In multilevel models, White females were more likely to smoke relative to non-White females and males (OR = 1.42, 95%CI:1.06-1.89). Youth with a strong sense of community belonging and living in deprived neighborhoods were at increased risk of smoking (OR = 1.18, 95%CI:1.06-1.32). The individual-level risk factor, household smoker, contributed substantially to youth smoking reducing the bivariate association between material deprivation and smoking by 33%. CONCLUSION: White females, youth cohabiting with other smokers and youth living in poor neighborhoods with a strong sense of community belonging, are at an increased risk of smoking. Future anti-smoking efforts might have greater impact if they target at-risk youth as well as household members who cohabit with youth.

Neighbourhood deprivation and regional inequalities in self-reported health among Canadians: are we equally at risk?

Individual-level data from the Canadian Community Health Survey was combined with area-level data from the 2001 Canada Census to explore the relationship between neighbourhood deprivation and regional inequalities in self-reported health (n=120,290). While neighbourhood deprivation was a significant predictor of fair/poor health in all geographic regions (OR=1.11; 95% CI: 1.08, 1.14), living on the Atlantic and Pacific coasts exacerbated the detrimental effects of neighbourhood deprivation on the perceived health of respondents (OR=1.21; 1.28). By failing to explore regional variations in risk, we could fail to identify areas where provincial policies may interact with neighbourhood factors to reinforce health inequalities amongst deprived communities.

Neighbourhood chronic stress and gender inequalities in hypertension among Canadian adults: a multilevel analysis.

BACKGROUND: A growing body of literature regarding the contextual influences of 'place' effects on health increasingly demonstrates that living in neighbourhoods with high levels of deprivation is associated with worse cardiovascular outcomes; however, little research has explored whether neighbourhood deprivation has a differential impact on the cardiovascular health of men and women. The purpose of this study was to explore gender differences in the association between neighbourhood deprivation and the prevalence of hypertension among non-institutionalised Canadian adults. METHODS: Individual-level data from the Canadian Community Health Survey (2000-2005) were combined with area-level data from the 2001 Canada Census to assess the relationship between gender, neighbourhood deprivation and hypertension using multilevel regression. RESULTS: Of the 103,419 respondents, 20 705 reported having hypertension (17.6%). In multilevel models, neighbourhood deprivation was significantly associated with hypertension and this effect remained significant after adjusting for individual-level demographic, socioeconomic and lifestyle characteristics (OR 1.12, 95% CI 1.10 to 1.15). Neighbourhood deprivation appears to be a stronger predictor of hypertension among women, such that women living in areas of high deprivation were 10% more likely to report having hypertension in comparison with men living in the same neighbourhoods and with women living in the least impoverished neighbourhoods. CONCLUSIONS: Although future research is needed to determine whether interventions at the area-level are effective in reducing inequalities in health outcomes across neighbourhoods, policies aimed at reducing area-level deprivation may have a differential benefit on the cardiovascular health of men and women.