Social Determinants of Health among Older Adults with Dementia in Urban and Rural Areas.

BACKGROUND: Social determinants of health (SDOH) may influence health in people living with dementia. Little is known about SDOH differences in urban compared to rural dwelling people living with dementia. OBJECTIVES: To explore urban-rural differences in SDOH in people living with mild cognitive impairment (MCI) and dementia. DESIGN: Descriptive study. SETTING/PARTICIPANTS: People ≥55 years with MCI or dementia empaneled to Community Internal Medicine at Mayo Clinic (Rochester, MN, USA) who completed SDOH questions between June 1, 2019 and June 30, 2021 were included. MEASUREMENTS: SDOH questions addressed education, depression, alcohol use, financial strain, food insecurity, physical activity, social connections, stress and transportation. SDOH data were compared by location based on Rural-Urban Commuting Areas Codes. RESULTS: Of 3552 persons with MCI (n=1495) or dementia (n=2057), 62% lived in urban areas, 19% in large rural, 10% in small rural and 9% in isolated areas. Approximately 60% were physically inactive, 20% socially isolated and 30% had stress concerns. Rural patients experienced greater financial strain (p=0.003). CONCLUSION: Social isolation, stress and physical inactivity are common in people living with MCI and dementia across urban and rural areas. Targeted interventions to improve physical and psychosocial health could have great impact in this population.

Impact of weight bias and stigma on quality of care and outcomes for patients with obesity.

The objective of this study was to critically review the empirical evidence from all relevant disciplines regarding obesity stigma in order to (i) determine the implications of obesity stigma for healthcare providers and their patients with obesity and (ii) identify strategies to improve care for patients with obesity. We conducted a search of Medline and PsychInfo for all peer-reviewed papers presenting original empirical data relevant to stigma, bias, discrimination, prejudice and medical care. We then performed a narrative review of the existing empirical evidence regarding the impact of obesity stigma and weight bias for healthcare quality and outcomes. Many healthcare providers hold strong negative attitudes and stereotypes about people with obesity. There is considerable evidence that such attitudes influence person-perceptions, judgment, interpersonal behaviour and decision-making. These attitudes may impact the care they provide. Experiences of or expectations for poor treatment may cause stress and avoidance of care, mistrust of doctors and poor adherence among patients with obesity. Stigma can reduce the quality of care for patients with obesity despite the best intentions of healthcare providers to provide high-quality care. There are several potential intervention strategies that may reduce the impact of obesity stigma on quality of care.

In situ simulation training for paediatric cardiorespiratory arrest: initial observations and identification of latent errors.

In response to a successful, although difficult resuscitation in one of our paediatric wards, we developed and implemented an educational program to improve the resuscitation skills, teamwork and safety climate in our multidisciplinary acute-care paediatric service. The program is ongoing and consists of didactic presentations, high-fidelity in situ simulation and facilitated debriefing to encourage reflective learning. The underlying goal, to provide this training to all staff over a two-year period, should be achieved by late 2011. In this preliminary report we describe teamwork difficulties that are commonly found during such training. These included inconsistent leadership behaviours, inadequate delegation of areas of responsibility, failure to communicate problems during the execution of technical tasks (such as difficulty opening the resuscitation trolley) and failure to challenge inadequate or inappropriate therapy (such as poor chest expansion during bag-mask ventilation). In addition, we unexpectedly discovered seven latent errors in our clinical environment during the first nine months of course delivery. The most disturbing of these was that participants repeatedly struggled to identify and overcome the locking-mechanism and tamper-proof device on a newly introduced resuscitation trolley.

Modelling the demographics of the Irish cattle population.

In recent years, national authorities have committed very substantial resources to the creation and maintenance of databases capable of recording important animal event data, such as births, deaths and movements. This has primarily been driven by the need to ensure the quality and safety of animal products. However, it can also be used to assist policy makers in decision making. Despite the abundance of animal event data, as yet there is little published information about the use of these data to better understand the demography of cattle populations. This study reports the development of, and outputs from, a demographic model using data routinely collected from the Irish cattle population. The demographic model was based on a series of life tables detailing age-specific probabilities of survival up to a maximum of 17 years. These outputs were used to determine characteristics of the Irish cattle population, including estimated mortality rates, life expectancies and age profiles, and estimated cattle numbers by age and date. Separate life tables were developed for each of the 204 monthly birth cohorts born between January 1989 and December 2005. Within the Irish cattle population, the peak estimated mortality rate occurs at 29-33 months. The estimated life expectancy at birth of cattle in Ireland was 42 months. When the survival rates for all the cohorts within a population are calculated, then it is possible to use these rates as a model for determining future population size and answering cohort specific queries.

The effect of varying levels of population control on the prevalence of tuberculosis in badgers in Ireland.

We examined the effect of varying levels of badger population control on the prevalence of Mycobacterium bovis infection in badgers in four counties of Ireland. In the 'Removal' and 'Buffer' areas, proactive culling was conducted to substantially reduce and subsequently maintain badger populations at a low level for five years. In the 'Reference' areas, localised reactive culling was conducted in association with herd breakdowns. The infection status of badgers was determined using bacteriology. A total of 2696 badgers were recruited into the study, and 19.0% were found to be infected with M. bovis. The two population control strategies had differing effects on the subsequent prevalence of tuberculosis in badger populations. Proactive culling led to a long term decrease in the prevalence of tuberculosis in the re-emergent populations. Although there was an overall decline in the disease prevalence, no consistent trend in disease prevalence as a result of reactive culling was observed.

The impact of badger removal on the control of tuberculosis in cattle herds in Ireland.

In Ireland, the herd prevalence of bovine tuberculosis has remained stable for several decades, and in common with several other countries, progress towards eradication has stalled. There is evidence in support of the potential role of infected badgers (Meles meles, a protected species) in bovine tuberculosis in Ireland and Britain. However, this evidence on its own has not been sufficient to prove disease causation. Field trials are likely to offer the best opportunity to define this role. Building on the earlier East Offaly project, our objectives were to assess the impact of badger removal on the control of tuberculosis in cattle herds in Ireland. The study was conducted from September 1997 to August 2002 in matched removal and reference areas (average area of 245.1km(2)) in four counties: Cork, Donegal, Kilkenny and Monaghan. Badger removal was intensive and proactive throughout the study period in the removal areas, but reactive (in response to severe tuberculosis outbreaks in cattle) in the reference areas. Removal intensity in the removal and reference areas during the first 2 years of the study averaged 0.57 and 0.07 badgers/km(2)/year, respectively. The outcome of interest was restriction of cattle herds due to confirmed tuberculosis, where tuberculous lesions were detected in one or more animals. Data were analysed using logistic regression (modelling the probability of a confirmed herd restriction) and survival analysis (modelling time to a confirmed herd restriction). During the study period, there was a significant difference between the removal and reference areas in all four counties in both the probability of and the time to a confirmed herd restriction due to tuberculosis. In the final year of the study, the odds of a confirmed herd restriction in the removal (as compared to the reference areas) were 0.25 in Cork, 0.04 in Donegal, 0.26 in Kilkenny and 0.43 in Monaghan. Further, the hazard ratios (removal over reference) ranged from 0.4 to 0.04 (a 60-96% decrease in the rate at which herds were becoming the subject of a confirmed restriction).

Epidemiology and control of an outbreak of foot-and-mouth disease in the Republic of Ireland in 2001.

An outbreak of foot-and-mouth disease was confirmed in a flock of sheep on a farm in the Cooley peninsula, County Louth, on March 22, 2001. The virus was similar to other viruses of the serotype O PanAsian strain and virtually indistinguishable from other isolates from Northern Ireland and Great Britain. The epidemiological evidence suggested that infected sheep brought from Great Britain on February 19, 2001, were the source of the infection. The disease was eradicated by epidemiological investigation, serological testing and extensive culling.

Bovine tuberculosis in badgers in four areas in Ireland: does tuberculosis cluster?

We described the distribution of badger populations in four different areas in the Republic of Ireland. The data came from periodic targeted badger-removal and subsequent post-mortem examinations conducted between 1989 and September 1997, and from a formal badger-removal project in the same areas from 1997 through 1999. Records were complete for 2292 badgers regarding the date of capture, tuberculosis status, geographical area and specific sett from where the badgers were snared. Of 3187 setts, 2290 had no badgers recorded against them (i.e. were inactive). The badger-level prevalence of tuberculosis differed among areas (range 13-29%). Badger populations were highly clustered by sett, and this result was similar over the four study areas. The median number of badgers per active sett was 2. Tuberculous badgers also clustered within a sett. The third quartile of tuberculous badgers was 1 per active sett. The prevalence of tuberculous badgers within a sett was not related to the total number of badgers. There was little evidence of spatial clustering with only one local cluster of tuberculous setts in each of three areas, and none in the fourth area. After adjusting for the number of badgers per sett, only one area had spatial clusters identified.

Stressful life events and physical abuse among pregnant women in North Carolina.

OBJECTIVES: This study estimates the prevalence of stressful life events and physical abuse among North Carolina women prior to infant delivery, and examines potential associations between abuse and the other stressors. METHODS: Data were from the North Carolina Pregnancy Risk Assessment Monitoring System, a statewide representative survey of over 2,600 postpartum women. The survey assessed women's sociodemographic characteristics and their experiences of physical abuse and 13 other stressful life events before delivery. The prevalences of each life event and abuse were estimated. Logistic regression modeled the probability of women having high levels of stressful life events in relation to physical abuse and sociodemographics. RESULTS: Most women were married, white, high school graduates, aged 20 or older. The most common stressful life events were residential moves, increased arguing with husbands/partners, family member hospitalizations, financial hardship, and deaths of loved ones. Fourteen percent of women had high levels of stressful events (5 or more), and almost 9% were physically abused. Abuse was positively associated with increased arguing with husbands/partners, physical fighting, having someone close with an alcohol/drug problem, becoming separated/divorced, and financial hardship. Logistic regression analysis showed that a high level of stressful life events was significantly more likely among women abused both before and during pregnancy (OR = 11.94) and among women abused before but not during pregnancy (OR = 14.19). CONCLUSIONS: The high frequency of multiple stressful events and abuse in women's lives suggests that women's care providers should ask their patients about these issues, and offer appropriate referral/interventions to those in need.

Race, clinical factors and pre-term birth in a low-income urban setting.

UNLABELLED: While infant mortality rates have declined for both White and African-American populations, the perennial two-fold excess in risk for African Americans remains unchanged, and indeed, may have increased since 1985. One potential explanation for the excess risk in African Americans might be racial differences in maternal clinical risk factors, such as prior pregnancy history and pregnancy complications. This paper examines the contributions of such clinical indicators to racial differences in pre-term delivery in a study sample of urban, low-income women, aged 18 to 43 years. METHODS: Study participants were enrolled during their first prenatal care visit at one of four hospital-based, prenatal care clinics in Baltimore City. Medical history and pregnancy outcome data were abstracted from clinical records. Multiple logistic regression models were used to assess the independent relationship between race and pre-term birth, after controlling for clinical factors. RESULTS: Without adjustment for clinical risk factors, African-American women were 1.8 times more likely than White women to have a pre-term birth outcome (95% confidence interval 1.20-2.78). After statistical adjustment for the clinical variables, however, the association between race and pre-term birth was diminished (OR = 1.64, 95% confidence interval: 0.99-2.72). Moreover, the associations between certain clinical risks and pre-term birth were stronger for African-American than White women. CONCLUSION: These results suggest that attention to clinical risk factors among African-American women may be an important avenue for reducing Black/White racial disparities in pre-term birth.

CD4(+) T-cell activation and induction of autoimmune hepatitis following trichloroethylene treatment in MRL+/+ mice.

Exposure to relatively high levels of trichloroethylene has recently been shown to accelerate the development of an autoimmune response in the autoimmune prone MRL+/+ mice. The trichloroethylene-induced autoimmune response was associated with an increase in activated CD4(+) T cells, producing Th(1)-like cytokines. The present study was conducted to determine whether lower, more occupationally relevant doses of trichloroethylene could also promote autoimmunity, in MRL+/+ mice, and if so, to investigate the mechanism of this accelerated autoimmune response. In addition, histological studies were performed to determine if trichloroethylene was capable of producing pathological markers consistent with an autoimmune disease. Trichloroethylene was administered to mice in the drinking water at 0, 0.1, 0.5, and 2.5 mg/ml for 4 and 32 weeks. There was a significant increase above controls in serum antinuclear antibody (ANA) levels following 4 weeks of both 0.1 and 0.5 mg/kg/day of trichloroethylene. After 32 weeks of treatment, ANA levels were elevated and equal in all groups. The kinetics of the ANA response indicated that trichloroethylene accelerated the innate autoimmune response in the MRL+/+ mice. There was a dose-related increase in the percentage of activated CD4(+) T cells in both the spleens and lymph nodes of mice treated for 32 weeks with trichloroethylene when compared to controls. CD4(+) T cells isolated from MRL+/+ mice after either 4 or 32 weeks of treatment with trichloroethylene secreted inflammatory or Th(1)-like cytokines. Following 32 weeks of trichloroethylene treatment, there was a significant increase in hepatic mononuclear infiltration localized to the portal region, a type of hepatic infiltration consistent with autoimmune hepatitis. Taken collectively, these data suggest that exposure to occupationally relevant concentrations of trichloroethylene can accelerate an autoimmune response and can lead to autoimmune disease. The mechanism of this autoimmunity appears to involve, at least in part, activated CD4(+) T cells that then produced inflammatory cytokines.

Inhibition of CYP2E1 reverses CD4+ T-cell alterations in trichloroethylene-treated MRL+/+ mice.

Trichloroethylene is an organic solvent that is primarily used as a degreasing agent for metals. There is increasing evidence in both humans and animal models that trichloroethylene promotes the development of autoimmunity, but little is known about the mechanisms that mediate the effect of trichloroethylene on the immune system. Metabolic activation of trichloroethylene is considered an obligatory pathway for other known toxicities such as hepatotoxicity, nephrotoxicity, and carcinogenicity. Trichloroethylene is metabolized by the cytochromes P450, primarily cytochrome P450 2E1 (CYP2E1). To investigate whether metabolism by CYP2E1 is required for immunomodulation, we treated autoimmune prone MRL+/+ mice with trichloroethylene in the drinking water for 4 weeks, in the presence or absence of diallyl sulfide, a specific inhibitor of CYP2E1. Using an antibody that recognizes proteins covalently modified by a reactive metabolite of trichloroethylene; two immunoreactive proteins were detected in liver microsomes from trichloroethylene-treated mice. Formation of these trichloroethylene-protein adducts, an indicator of metabolic activation, was completely inhibited in animals that were concomitantly treated with trichloroethylene and diallyl sulfide. The level of CYP2E1 apoprotein in liver microsomes was significantly reduced in the presence of diallyl sulfide. The enhanced mitogen-induced proliferative capacity of T cells from trichloroethylene-treated MRL+/+ mice was inhibited if the mice were also treated with diallyl sulfide. In addition, the reduction in interleukin-4 levels secreted by activated CD4+ T cells from trichloroethylene-treated mice was reversed if the mice were also treated with diallyl sulfide. Taken collectively, metabolism of trichloroethylene by CYP2E1 is responsible, at least in part, for the CD4+ T cell alterations associated with exposure to this environmental toxicant.

Trichloroethylene accelerates an autoimmune response by Th1 T cell activation in MRL +/+ mice.

Trichloroethylene (1,1,2-trichloroethene) is a major environmental contaminant. There is increasing evidence relating exposure to trichloroethylene with autoimmunity. To investigate potential mechanisms, we treated the autoimmune-prone MRL +/+ mice with trichloroethylene in the drinking water at 0, 2.5 or 5.0 mg/ml and sacrificed them at 4, 8 and 22 weeks. As early as 4 weeks of treatment, Western blot analysis showed a dose-dependent increase in the level of trichloroethylene-modified proteins, indicating that a reactive metabolite of trichloroethylene was formed. Significant increases in antinuclear antibodies (ANA) and total serum immunoglobulins were found following 4-8 weeks of trichloroethylene treatment, indicating that trichloroethylene was accelerating an autoimmune response. Investigation into possible mechanisms of this autoimmune response revealed that trichloroethylene treatment dramatically increased the expression of the activation marker CD44 on splenic CD4+ T cells at 4 weeks. In addition, splenic T cells from mice treated for 4 weeks with trichloroethylene secreted more IFN-gamma and less IL-4 than control T cells, consistent of a T-helper type 1 (Th1) type immune or inflammatory response. A specific immune response directed against dichloroacetylated proteins was found at 22 weeks of trichloroethylene treatment. Taken collectively, the results suggest that trichloroethylene treatment accelerated an autoimmune response characteristic of MRL +/+ mice in association with nonspecific activation of Th1 cells. In addition, long-term treatment with trichloroethylene led to the initiation of a trichloroethylene-specific immune response.

Trichloroethylene activates CD4+ T cells: potential role in an autoimmune response.

Trichloroethylene is an industrial solvent and has become a major environmental contaminant. Autoimmune-prone MRL +/+ mice were treated for up to 22 weeks with trichloroethylene in the drinking water (0, 2.5, and 5.0 mg/mL) in order to study the immunoregulatory effects of this environmental toxicant. After only 4 weeks of treatment, trichloroethylene was shown to promote the expansion of CD4+ T cells that expressed a memory/activation phenotype (i.e., CD44hi CD45RBlo) and secreted high levels of IFN-gamma, but not IL-4. In addition, trichloroethylene treatment accelerated the development of an autoimmune response in the MRL +/+ mice as evidenced by an earlier appearance of antinuclear antibodies and increased levels of total IgG2a. MRL +/+ mice treated with trichloroethylene for 22 weeks also contained antibodies specific for trichloroethylene adducts, suggesting the activation of trichloroethylene-specific T cells. The results suggest that trichloroethylene can stimulate antigen nonspecific as well as specific T cells that are capable of promoting autoimmunity in genetically predisposed individuals.

Covalent binding of trichloroethylene to proteins in human and rat hepatocytes.

The environmental contaminant and occupational solvent trichloroethylene is metabolized to a reactive intermediate that covalently binds to specific hepatic proteins in exposed mice and rats. In order to compare covalent binding between humans and rodents, primary hepatocyte cultures were exposed to vaporized trichloroethylene at 0-10,000 parts per million for up to 2 h. Immunochemical detection of three major dose- and time-dependent trichloroethylene protein adducts at 50, 52 and 100 kDa was demonstrated in the rat hepatocytes, while a single, distinctively different 47 kDa adduct was detected in human hepatocytes. The 50 kDa adduct in rat hepatocytes was found to comigrate on SDS-PAGE with cytochrome P450 2E1 (CYP2E1), while the adduct found in humans did not comigrate with CYP2E1. These data show that reactive metabolites of trichloroethylene can be formed in human and rat hepatocytes and bind covalently to discrete hepatic proteins, and suggests that in rats, but not humans, that one of the targets is CYP2E1.

The effect of a badger removal programme on the incidence of tuberculosis in an Irish cattle population.

The risk of a confirmed tuberculous herd restriction was examined using a logistic model for herds involved in the East Offaly Badger Research Project, Ireland, from 1988-1995. Cattle herds present in the badger-removal area had a significantly lower proportion of new confirmed tuberculous herd restrictions compared with cattle from an area where no systematic badger removal was attempted.

The association between the bovine tuberculosis status of herds in the East Offaly Project Area, and the distance to badger setts, 1988-1993.

The proximity of farms to badger setts was compared between farms that had experienced a tuberculosis breakdown and those that had not, over the 6 year period from 1988 to 1993. The data were derived from a badger removal study conducted in East Offaly County in the Republic of Ireland. Badger removal began in 1989 and continued through 1993; by the end of 1990, approximately 80% of all badgers caught in the 6 year period had been removed. All badgers were examined, grossly, for evidence of tuberculosis. Tuberculosis status of the approximately 900 study herds was based on the results of the single intradermal comparative skin test and/or lesions of bovine tuberculosis. All herds were tested at least once annually. The number of herds experiencing bovine tuberculosis declined over the period, particularly in the years 1992 and 1993. The data on farm and badger sett location were stored and analysed, initially, in a geographical information system. Owing to the badger removal programme, the distance between the barn yard of a typical farm and the nearest occupied badger sett increased, by about 300 m year-1, and by about 600 m year-1 to the closest infected sett. In bivariate analyses, in the years 1988 and 1989, the risk of tuberculosis declined with increasing distance to a badger sett containing one or more tuberculous badgers. In multivariable logistic regression analyses, year and the average number of cattle tested per farm per year were controlled. A second identical analysis was conducted to control for the repeated observations on the same herds using generalised estimating equations. In both analyses, the risk of a multiple reactor tuberculosis breakdown decreased for herds at least 1000 m away from an infected badger sett, and increased as the number of infected badgers per infected sett increased. Despite the significantly reduced risk of a breakdown with increasing distance to infected badger setts, the relationship was not strong (sensitivity and specificity of the model in the low 70% range) and explained only 9-19% of tuberculosis breakdowns.

Hypoxia and proliferation are primarily responsible for induction of lactate dehydrogenase activity in cultured cells.

In vitro to in vivo extrapolations require cellular models that closely mimic cells in vivo. Typically, cultured cells revert to glycolysis, have increased lactate dehydrogenase (LDH) activity, have decreased oxidative metabolism, and dedifferentiate. This study examined the role of hypoxia and proliferation in the regulation of LDH activity, and the temporal relationships among induction of glycolysis, LDH activity, and proliferation in primary cultures of rabbit renal proximal tubular cells (RPTC). LDH activity in RPTC grown under standard conditions (STILL) did not increase during the first 3 d of culture, but increased 18-fold by d 7. LDH activity in RPTC grown under conditions of increased oxygen supply (SHAKE) did not increase during the first 3 d of culture, but increased 5.5-fold by d 7. Hypoxia and proliferation were responsible for 73% and 27%, respectively, of the increase in LDH activity in STILL RPTC. Hypoxia had no effect on RPTC proliferation. Neither medium glucose nor insulin concentrations had any effect on LDH activity in SHAKE RPTC. Supplementation of the culture medium with ribose 5-phosphate or ribose diminished the increase in LDH activity in SHAKE RPTC to 62% and 52% of controls but had no effect on monolayer DNA content. Two-day treatment of confluent SHAKE RPTC with epidermal growth factor (EGF) resulted in 1.6-, 1.4-, and 1.9-fold increases in LDH and G6PDH activities and monolayer DNA content, respectively. The stimulatory effect of EGF on LDH and G6PDH activities, but not monolayer DNA content, was abolished by ribose or ribose 5-phosphate. In contrast, transforming growth factor-beta 1 (TGF-beta 1) treatment stimulated lactate production but had no effect on LDH and G6PDH activities, or proliferation of SHAKE RPTC. These results show that (1) both hypoxia and proliferation are primarily responsible for the induction of LDH activity in cultured cells, (2) LDH activity is not an accurate indicator of glycolysis, (3) induction of LDH activity is secondary and due, in part, to the induction of the pentose phosphate pathway, (4) EGF stimulates glycolysis, LDH activity, and proliferation, and (5) TGF-beta 1 stimulates glycolysis but has no effect on LDH activity or proliferation.

James B. Connolly, First modern Olympic champion. The Georgia Connection, Circa 1896.

As the centennial Olympic Games come to Atlanta in 1996, and the sailing venue to Savannah, it is only fitting that the first modern Olympic champion had some connection to the state of Georgia, the city of Savannah, and the art of sailing. James Brendan Connolly was not only a terrific athlete, but a noted writer and adventurer. Moreover, he was the type of man who impressed even the President of the United States with his sterling qualities. The latter serve as a shining example a century after his initial Olympic exploits.