Activity-based assessment of an engineered hyperthermophilic protein as a capture agent in paper-based diagnostic tests.

Antibodies have traditionally served as the affinity reagents of choice in point-of-care diagnostic biosensors. However, this class of proteins is not ideally suited for this use, being poorly characterized and prone to thermal denaturation. Here, we present an activity-based assessment of an alternative engineered binding protein in a cellulose-based assay.

Vpx-containing dendritic cell vaccine induces CTLs and reactivates latent HIV-1 in vitro.

Eradication of human immunodeficiency virus-1 (HIV-1) from an infected individual requires a means of inducing production of virus from latently infected cells and stimulating an immune response against the infected cells. We report the development of lentiviral vectors that transduce dendritic cells (DCs) to both induce production of virus from latently infected cells and stimulate antigen-specific cytotoxic T lymphocytes (CTLs). The vectors package Vpx, a lentiviral accessory protein that counteracts the SAMHD1-mediated block to DC transduction, allowing for long-term expression of vector-encoded proteins. The vectors encode influenza or HIV-1-derived epitopes fused via a self-cleaving peptide to CD40L that releases the peptide into the endoplasmic reticulum for entry into the antigen presentation pathway. Expression of CD40L caused transduced DCs to mature and produce Th1-skewing cytokines. The DCs presented antigen to CD8 T cells, enhancing antigen-specific CTLs. Coculture of the transduced DCs with latently infected cells induced high-level virus production, an effect that was mediated by tumor necrosis factor alpha. The ability of a DC vaccine to reactivate latent HIV-1 and stimulate an adaptive immune response provide a means to reduce the size of the latent reservoir in patients. This strategy can also be applied to develop DC vaccines for other diseases.

Test of recrudescence hypothesis for overwintering of West Nile virus in gray catbirds.

West Nile virus is a pathogen of concern for both human and wildlife health. Although many aspects of the ecology of West Nile virus are well understood, the mechanisms by which this and similar mosquito-borne viruses overwinter and become reinitiated each spring in temperate regions is not known. A thorough understanding of this mechanism is crucial to risk assessment and development of control strategies. One of the hypotheses to explain the mechanism by which this virus persists from year to year is the spring recrudescence of latent virus in avian reservoir hosts. Stress-related immunosuppression is implicated in the recrudescence of latent viruses in birds. We tested the spring recrudescence hypothesis in a controlled laboratory experiment using hatching-year gray catbirds (Dumatella carolinensis) captured in northern Ohio (July-August 2006). Catbirds (n = 60) were experimentally infected (September 2006) and later examined for the effects of immunosuppression through exogenous hormones and artificially induced migratory disposition. We found no effect of either testosterone or migratory behavior on infection status in any of the treatment birds. Moreover, we detected no viral RNA in the kidney, spleen, brain, or liver upon necropsy at 24 wk postinfection.

Assessing the relationship between health utilities, quality of life, and health care costs in Alzheimer's disease: the CATIE-AD study.

OBJECTIVES: To examine the relationship between multiple measures of health care costs and health utilities, quality of life, and other factors in Alzheimer's Disease (AD). RESEARCH DESIGN: Data were obtained via caregiver proxy at baseline and 3- 6- and 9-months following study entry on 421 patients with AD who participated in the CATIE-AD trial of antipsychotic medication. Spearman rank correlations and mixed models (using logged costs) were used to examine the correlates of health care costs. MEASURES: Health care costs include inpatient hospital, nursing home, residential care, combined institutional, outpatient, ancillary drug, and total costs. Correlates include the AD-Related Quality of Life Scale (ADRQoL) and Health Utilities Index (HUI)-III. RESULTS: Total monthly health care costs averaged $1,205 during the study period. Each .10 increment on the HUI-III (stronger health utilities) was associated with a decrease in institutional, outpatient, and total costs of 9.7%, 6.9%, and 8.2%, respectively. Each one-point increase on the ADRQoL (better quality of life) was associated with an increase in ancillary drug and total costs of 1.7% and 2.1%. Total costs tended to be lower for female patients (beta=-.325) with better physical functioning (beta=-.017) but higher for less cognitively impaired individuals (beta=.038). Older (beta=.025), non-Hispanic Whites (beta=.575) tended have higher outpatient costs, those with better physical functioning lower institutional costs (beta=-.019). Drug costs tended to be lower for females (beta=-.427) and higher for those with greater psychiatric symptoms (beta=.016). CONCLUSION: The HUI-III findings suggest that health utilities could be combined with other known correlates of costs to inform resource allocation cost-effectiveness analyses associated with AD. The ADRQoL findings suggest that better quality of life may make it easier for caregivers to identify problems and/or to access and maintain certain types of health system contacts.

Health information Websites: characteristics of US users by race and ethnicity.

We conducted a national public opinion survey of adults aged 18 years or older in the continental US to determine their use of health Websites. Of the 928 individuals contacted, 868 (94%) reported their race/ethnicity. More non-Hispanic Whites reported using the Internet (34%) than African Americans (31%) and Hispanics (20%). We used logistic regression to estimate adjusted odds ratios describing the relationship between Website usage and covariates across the racial/ethnic subgroups. Whereas better perceived health was associated with greater Website use among Hispanics and Whites, stronger health literacy was associated with greater use among Hispanics. No African American or Hispanic respondent aged 65 years or older reported going online. The relationship between education and use was more than twice as strong for African Americans and Hispanics than other groups. That some minority groups are less likely to use the World Wide Web for health information may further compound existing disparities. One place where this problem may be addressed is in the nation's schools.

Combination of flavor enhancement and chemosensory education improves nutritional status in older cancer patients.

BACKGROUND: Abnormalities in taste and smell functioning occur with elevated frequency in both older adults and patients with cancer. With the predicted increase in both of these populations in the coming decades, it is imperative to evaluate potential interventions that are designed to help older cancer patients compensate for the additive burden of this disease and its treatment on age-related taste and smell losses. OBJECTIVE: The purpose of the current study was to determine if providing instruction and products for flavor enhancement of foods to elderly cancer patients in addition to nutritional information would improve their nutritional status, and, by extension, functional and immune status as well as quality of life. DESIGN: One hundred and seven subjects enrolled in the study. Fifty-four subjects were in the experimental group that received flavor enhancement plus nutritional information; fifty-three control subjects received only nutritional information. Subjects were evaluated 1 month, 3 months, and 8 months after beginning chemotherapy. At every session, subjects completed taste and smell assessments as well as questionnaires related to nutritional status, activities of daily living, and quality of life. Blood samples were also obtained to determine immune parameters. RESULTS: At the eight-month time point, experimental subjects had better scores on the mini nutritional assessment (MNA) and the physical function assessment of the quality of life questionnaire. Also at eight months, self-reported taste and smell perception for experimental subjects was better than that of controls as well as better than at earlier time points. Tests that assessed quantity and quality of food intake, as well as a number of immune parameters declined over time and did not differ significantly between groups. CONCLUSION: The combination of flavor enhancement, chemosensory education, and nutritional information for elderly cancer patients improved their nutritional assessment on the MNA and physical function over time. On the whole, experimental subjects perceived themselves to be better functioning at eight months than did their control counterparts.

The functional and psychosocial impact of fecal incontinence on women with urinary incontinence.

OBJECTIVES: The study was undertaken to determine the impact of fecal incontinence (FI) on functional status and quality of life in women with urinary incontinence (UI). STUDY DESIGN: In 24 months 732 women completed a standardized assessment and questionnaire, including the Short Form (SF)-12 and Incontinence Quality of Life (I-QOL) scores. Analysis of variance was used to compare SF-12 scores between groups defined as having UI, FI, or both UI and FI. I-QOL scores in patients with UI or UI and FI were compared by using the Student t test. RESULTS: Of the 732 patients enrolled, 425 patients had either UI (n = 342, 80%), FI (n = 18, 4%), or both (n = 65, 15%). Greater impairment in physical functioning was seen in the group with UI and FI (38.6; P =.027) compared with the group with UI (42.4). Significant decreases in I-QOL scores were seen for the group with UI and FI compared with those with UI (P <.005). CONCLUSION: Fecal incontinence further reduces the functional status and quality of life of women with urinary incontinence.

Steroidogenic responses of pig corpora lutea to insulin-like growth factor I (IGF-I) throughout the oestrous cycle.

This study was designed to investigate the roles of insulin-like growth factor I (IGF-I), IGF-type I receptor (IGF-IR) and IGF-binding proteins (IGFBPs) in regulating progesterone secretion by pig corpora lutea during the oestrous cycle, and the signal transduction pathways involved in mediating the steroidogenic actions of IGF-I. Corpora lutea were collected on days 4, 7, 10, 13 and 15 or 16 of the oestrous cycle, enzyme dissociated and the luteal cells were cultured for 24 h in Medium 199 with IGF-I (0-100 ng ml(-1)), long R(3)-IGF-I (0-100 ng ml(-1)), anti-IGF-I (Sm 1.2B; 0-10 microg ml(-1)), anti-IGF-IR (alphaIR3; 0-2 microg ml(-1)), or IGF-I signal transduction pathway inhibitors (phosphatidylinositol (PI)-3-kinase: 100 nmol Wortmannin l(-1) and 10 micromol LY 294002 l(-1); MAP kinase: 50 micromol PD 98059 l(-1)) to investigate their effects on IGF-I (100 ng ml(-1)) stimulated progesterone secretion. Pig luteal cells displayed dose-dependent responses to IGF-I and long R(3)-IGF-I on days 4 and 7 of the oestrous cycle, but not on days 10-16. There was no difference in the ED(50) or V(max) (maximal response) values between IGF-I and long R(3)-IGF-I. Neither anti-IGF-I nor anti-IGF-IR had significant effects on progesterone secretion, at any dose or day. Wortmannin and LY 294002 blocked IGF-I stimulated progesterone secretion, but PD 98059 was without effect. Finally, IGF-I (6 microg) infused into the ovary on day 7 in vivo significantly increased progesterone secretion within 45 min of infusion. The conclusions of this study are: (1) IGF-I has steroidogenic actions only on 'young' (days 4-7) pig corpora lutea; (2) endogenous IGF-I and IGFBP are insufficient to modulate progesterone secretion in vitro; and (3) the steroidogenic actions of IGF-I are mediated via PI-3-kinase.

Taste, smell and neuropsychological performance of individuals at familial risk for Alzheimer's disease.

The purpose of the study was to determine whether there are chemosensory and neuropsychological changes that predate the onset of Alzheimer's disease in individuals at enhanced risk of developing the condition. To study this question, a unique sample of individuals (n = 33) was studied who were genetically at-risk for AD by virtue of documented multigenerational evidence of the disease (so-called multiplex families). The performance of at-risk individuals was evaluated on various smell, taste, and neuropsychological measures at baseline and 18 months later. Their performance was compared to a control group (n = 32) that was matched in age, gender, education, and race. At baseline the at-risk group performed worse than the control group on the chemosensory measures of phenethyl alcohol smell detection, smell memory, and taste memory, and on a memory measure involving recall of narrative information (Logical Memory I from the Wechsler Memory Scale- Revised). Across both sessions, the at-risk group had lower smell memory scores than the control group. At-risk status was not significantly associated with APOE status. The results of this and other studies suggest that individuals who are genetically at risk for developing AD may perform more poorly on memory and smell measures compared to those not at risk. This effect may be separate from one known genetic risk factor of AD, APOE, and supports that multiple genes are likely responsible for the disease and its associated memory and other neurocognitive symptoms.

Polymorphic repeats in the androgen receptor gene in high-risk sibships.

BACKGROUND: Genetic susceptibility may explain some familial clusters of prostate cancer. The polymorphic androgen receptor (AR) gene, which mediates androgen activity in the prostate, is a candidate gene that may influence predisposition to the disease. METHODS: We analyzed the polymorphic (CAG)n and (GGN)n repeats within the AR gene in men from 51 high-risk prostate cancer sibships, which included at least one affected and one unaffected man (n = 210). We compared repeat lengths of men with prostate cancer (n = 140) to their brothers (n = 70) without disease, stratified by median age at diagnosis of affected men within each sibship. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals to evaluate associations between prostate cancer and repeat length. RESULTS: The OR for prostate cancer associated with short (CAG)n repeats (< 22) compared to longer repeats (> or =22) was 1.13 (95% CI 0.5-2.4) overall, but was higher in sibships with a median age of <66 years at diagnosis (OR = 1.72, 95% CI 0.5-6.0). The (GGN)n array also was not associated with prostate cancer in general. However, in older men (> or = 66 years), there was a modest elevation in risk (OR = 1.56, 95% CI 0.6-4.1) among those with short repeats (GGN of < or =16). Men with both a short (CAG)n (< 22) and a short (GGN)n (< or =16) array were not at higher risk (OR = 1.06) compared to men with two long repeats [(CAG)n > or =22 and (GGN)n >16)]. CONCLUSIONS: These results suggest that the (CAG)n and (GGN)n repeats in the AR gene do not play a major role in familial prostate cancer.

Current management of vesicovaginal fistulae.

Vesicovaginal fistula continues to be a distressing problem that results most commonly from urogynecologic surgery. Several surgical techniques for correction of vesicovaginal fistulae have been described. The present review emphasizes those advances in surgical management and recent changes in etiology.

Suspected hypovitaminosis A in a colony of captive green anoles (Anolis carolinensis).

In a colony of 18 green anoles (Anolis carolinensis), 3 animals experienced focally thickened lips, ulcerative cheilitis, lethargy, depression, and weight loss over a 5-month period. In addition to crickets fed fresh fruit and leafy green vegetables, the diet of the green anoles consisted of a supply of mealworms that had been dusted with a commercial liquid vitamin supplement. The history, clinical findings, and histopathologic lesions were suggestive of hypovitaminosis A, which is known to cause squamous metaplasia of the mucus secreting glands and epithelial surfaces in many species.

Telemedicine and doctor-patient communication: an analytical survey of the literature.

The literature about the effect of telemedicine on doctor-patient communication was reviewed. A total of 38 studies were identified: six were surveys of provider and community attitudes; 21 were post-encounter surveys of participants in a medical consultation; and 11 were qualitative analyses of behaviour in a medical encounter. Twenty-one of the 38 investigations originated in the USA, six in the UK, four in Australia, three in Norway, two in Canada, one in Finland and one in Sweden. All were relatively recent. The findings from each study were coded according to 23 categories developed from the literature and a positive or negative rating was assigned to each of the 213 communication results. Approximately 80% of abstracted findings favoured telemedicine, with all but two of the 23 categories analysed (non-verbal behaviour and lack of touch) reporting more positive than negative results. Verbal content analysis is important for the development of interventions aimed at facilitating doctor-patient telecommunication. However, further research is necessary if the nature and content of the communication process are to be fully understood.

Incidence of four adverse outcomes in the elderly population: implications for home care policy and research.

The cost-effective allocation of home care resources requires knowledge of the incidence of institutionalization, hospitalization, functional impairment, and mortality. We therefore assembled a database containing 176 rates abstracted from 71 longitudinal studies published between 1985 and 1998 that examine one or more of these outcomes in the 65 and over population in the United States. Where possible we calculate median values for the estimated annual rate of each outcome for different types of studies-nationally representative, sub-national probability, and convenience sample-and specific subgroups-community residents, hospital admissions and discharges, and nursing home admissions and discharges. We find comparatively low rates of institutionalization and mortality, relatively high rates of hospitalization and functional impairment, similar rates for national and sub-national probability samples, and rates from convenience samples, which greatly exceed probability-based rates. While the rates for institutionalization, hospitalization and mortality are quite stable, the rates for functional impairment display considerably more variability. We conclude by discussing the implications of our findings for researchers and policymakers.

Monitoring plasma cardiac troponin I for the detection of myocardial injury after percutaneous transluminal coronary angioplasty.

The objective of this study was to detect myocardial injury defined by an increase of plasma cardiac troponin I (cTnI) following percutaneous transluminal coronary angioplasty (PTCA) and compare plasma cTnI with the risk of cardiac complications at 30 days. Plasma cTnI, creatine kinase (CK) MB, and total CK were determined in 83 patients before (baseline) and 6, 12 and 24 h after PTCA. Thirty-eight patients underwent conventional PTCA, 39 PTCA-stent and six rotational atherectomy. Patients with acute myocardial infarction (AMI) and increased pre-procedural cTnI >0.8 microg/l were categorized into group 1 (n=23). The remaining 60 patients (pre-procedural cTnI=0.8 microg/l) were categorized as follows: group 2 (n=15) AMI; group 3 (n=20) unstable angina (UA); group 4 (n=25) coronary artery disease (CAD). Twelve hours post-procedure, all three cardiac markers were more frequently increased over baseline in group 2 patients (40-60%) compared to patients in group 3 (5-29%, P<0.03) or group 4 (0.5-5%, P<0.01). This was also true for patients undergoing PTCA-stent compared to conventional PTCA or rotational atherectomy (27-40 vs. 4-14%, P<0.02). cTnI was more sensitive (60%) to detect release of myocardial protein after PTCA compared to total CK (47%) or CKMB (43%). A moderate increase of cTnI (0.8-1.5 microg/l) in groups 2, 3 and 4 was associated with higher risk of complications 30 days post-procedure.

Clinical evaluation of the first medical whole blood, point-of-care testing device for detection of myocardial infarction.

BACKGROUND: Validation of whole blood, point-of-care testing devices for monitoring cardiac markers to aid clinicians in ruling in and ruling out myocardial infarction (MI) is necessary for both laboratory and clinical acceptance. METHODS: This study evaluated the clinical diagnostic sensitivity and specificity of the First Medical Cardiac Test device operated by nursing and laboratory personnel that simultaneously measures cardiac troponin I (cTnI), creatine kinase (CK) MB, myoglobin, and total CK on the Alpha Dx analyzer in whole blood for detection of MI. Over a 6-month period, 369 patients initially presenting to the emergency department with chest pain were evaluated for MI using modified WHO criteria. Eighty-nine patients (24%) were diagnosed with MI. RESULTS: In whole blood samples collected at admission and at 3- to 6-h intervals over 24 h, ROC curve-determined MI decision limits were as follows: cTnI, 0.4 microgram/L; CKMB, 7.0 microgram/L; myoglobin, 180 microgram/L; total CK, 190 microgram/L. Based on peak concentrations within 24 h after presentation, the following sensitivities (+/- 95% confidence intervals) were found: cTnI, 93% +/- 5.5%; myoglobin, 81% +/- 9.7%; CKMB, 90% +/- 6.3%; total CK, 86% +/- 7.5%. Sensitivities were maximal at >90% for both cTnI and CKMB at >12 h in MI patients, without differences between ST-segment elevation and non-ST-segment elevation MI patients. CONCLUSIONS: The First Medical point-of-care device provides cardiac marker assays that can be used by laboratories and clinicians in a variety of hospital settings for ruling in and ruling out MI.

Elevated and sustained desire for sweet taste in african-americans: a potential factor in the development of obesity.

Oral habituation is a relatively long-lasting decrease in oral responsiveness that results from the repeated presentation of a single stimulus. The purpose of this study was to evaluate the degree of habituation to sweet-tasting foods and to determine whether there are differences in the rate of habituation between African Americans and European Americans. These two groups were compared because the prevalence of obesity and obesity-related disorders such as diabetes and hypertension is significantly higher among African Americans than among European Americans. Nine different commercial foods and beverages that differed in sweetness intensity and caloric density served as stimuli. Subjects tasted and rated each food once per minute for a 30-min period on scales related to desire for another taste of the same sample and desire for a different taste. The stimuli and portion size for each of the 30 samples were two candy bars (Ultra Slim-Fast Cocoa Almond Crunch Bar, 1/16 of a bar; Natural Nectar Peanut Butter Granola Bar, 1/16 of a bar), three beverages (Nestea Lemon Flavored Instant Tea with NutraSweet, 5 mL; Welch's Grape Juice, 5 mL; Pink Swimmingo Kool-Aid, 5 mL), two gelatin desserts (Cherry Flavored Jell-O Gelatin, 5 g; Cherry Flavored Jell-O Gelatin with NutraSweet, 5 g), one enteral nutrition drink (Vanilla Ensure Plus, 5 mL), and one pudding (Ultra Slim-Fast Chocolate Pudding, 5 g). Subjects consumed the entire portion of each sample. Habituation occurred for seven of the nine foods as judged by a decrease in the desire for another taste of the same food. The degree of habituation for European Americans and African Americans was similar except for the sweetest food (Cherry Flavored Jell-O Gelatin with NutraSweet), for which African Americans showed no habituation. The degree of habituation in both groups was unrelated to caloric density. Overall, young African Americans had a significantly greater desire for another taste of the same food than did young European Americans for seven of the nine foods, and this desire was strongly correlated with the sweetness intensity for young African Americans but not for young European Americans. Furthermore, young African Americans had a greater desire than young European Americans for a different taste for seven of nine foods. The greater desire for intense sweet tastes may be a factor in the elevated incidence of obesity and diabetes in African Americans. In addition, young African Americans had greater perceived stress in this study than did young European Americans. If African Americans use sweet taste to compensate for feelings of stress, this compensation may also contribute to weight gain.

Predicting elderly people's risk for nursing home placement, hospitalization, functional impairment, and mortality: a synthesis.

Long-term care resources would be allocated more cost-effectively if care planning and medical/functional eligibility decisions were grounded more firmly in extant evidence regarding the risk of nursing home placement, hospitalization, functional impairment, and mortality. This article synthesizes the studies that longitudinally assess the predictors of each of these outcomes for the 65 and older population in the United States. A database was assembled containing 167 multivariate analyses abstracted from 78 journal articles published between 1985 and 1998. Findings show that 22 risk factors consistently predict two or more outcomes, including three that predict all four: worse performance on physical function measures not based on activities of daily living, greater illness severity, and prior hospital use. Findings should help prioritize variable selection choices of those setting eligibility criteria, allocating care resources, and doing descriptive studies. Gaps are shown to exist in the understanding of outcome effects of facility, market, policy, and other system attributes.