Biopsychosocial Influences on Shoulder Pain: Analyzing the Temporal Ordering of Postoperative Recovery.

Shoulder surgery is a primary intervention for shoulder pain, yet many individuals experience persistent postoperative pain. Previously, we found individuals categorized as having a high-risk phenotype (comprised of COMT variation and pain catastrophizing) had approximately double the chance of not reaching a 12-month pain recovery criterion. As a means to better understand the development of persistent postoperative shoulder pain, this study advanced our previous work by examining temporal ordering of postoperative shoulder recovery based on potential mediating factors, and expansion of outcomes to include movement-evoked pain and shoulder active range of motion. Before surgery, individuals were categorized as either high-risk (high pain catastrophizing, COMT-genotype linked to low enzyme activity [n = 41]) or low-risk (low pain catastrophizing, COMT-genotype linked to normal enzyme activity [n = 107]). We then compared potential mediating variables at 3, 6, and 12 months postoperatively 1) endogenous pain modulation defined by a conditioned pain modulation paradigm; and 2) and emotion factors such as anxiety, fear of movement, and depressive symptoms. At 3 months, the high-risk subgroup had higher fear and movement-evoked pain, and causal mediation analysis confirmed the direct effect of risk subgroup on 12-month movement evoked pain. However, baseline to 12-month change in depressive symptoms were found to mediate 53% of the total effect of risk subgroup on 12-month movement-evoked pain. This study introduces potential temporal components and relationships to the development of persistent postoperative shoulder pain, which future studies will confirm and assess for potential therapeutic targets. PERSPECTIVE: This study expands upon postoperative shoulder recovery measures to include movement-evoked pain and depressive symptoms, and provides preliminary indication of temporal ordering to postoperative shoulder recovery for a preidentified high-risk subgroup. Future studies will distinguish temporal components of shoulder surgery that may optimize treatment targets of postoperative recovery.

Host susceptibility to severe influenza A virus infection.

Most people exposed to a new flu virus do not notice any symptoms. A small minority develops critical illness. Some of this extremely broad variation in susceptibility is explained by the size of the initial inoculum or the influenza exposure history of the individual; some is explained by generic host factors, such as frailty, that decrease resilience following any systemic insult. Some demographic factors (pregnancy, obesity, and advanced age) appear to confer a more specific susceptibility to severe illness following infection with influenza viruses. As with other infectious diseases, a substantial component of susceptibility is determined by host genetics. Several genetic susceptibility variants have now been reported with varying levels of evidence. Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age). These mechanisms may explain the prolonged viral replication reported in critically ill patients with influenza: patients with life-threatening disease are, by definition, abnormal hosts. Understanding these molecular mechanisms of susceptibility may in the future enable the design of host-directed therapies to promote resilience.

Are the Fitzpatrick Skin Phototypes Valid for Cancer Risk Assessment in a Racially and Ethnically Diverse Sample of Women?

The Fitzpatrick Skin Phototypes (FSP) were developed to classify skin color and response to ultraviolet radiation. FSP are used clinically to assess risk for sunburn and skin cancer. Our aim was to determine the criterion-related validity of self-reported FSP when compared with skin color and sunburn history, controlling for age, race/ethnicity, and seasonality/geography. We performed a secondary analysis of data (N=466) from an observational study. The racial/ethnic composition of the sample was 45% White/White Hispanic (WWH), 40% Black/Black Hispanic (BBH), and 15% Other Identities. Outcome measures were self-reported FSP and sunburn history, as well as physiological measures of skin color (L* lightness/darkness, a* redness/greenness, b* yellowness/blueness). Correlation between FSP and L* was -.77 (95% CI -.81, -.73; P<.001). Although 60% of the variance in FSP was accounted for by L* values for the entire sample, only 5% of the variance was accounted for among BBH participants (r=-.23), and up to 30% for WWH/Other Identity participants (r=-.48 and -.52). Multiple regression analysis indicated L* and b* values, sunburn history, and race/ethnicity, but not geography/seasonality or a* values significantly and collectively accounted for 72% of the variance in FSP. While the criterion validity of FSP was established by the strong relationship between L* values and FSP for the entire sample, when examined at the level of individual racial/ethnic subgroups, criterion validity of FSP was not demonstrated. When self-reported FSP are used for clinical skin assessment and sun cancer screening, they provide a restricted range of options for people with darker skin that does not capture variations in their skin color. Inaccuracy of clinical data may lead to unequal treatment or inadequate cancer risk assessment.

Estimación del riesgo cardiovascular de por vida (IBERLIFERISK): una herramienta nueva en prevención primaria de las enfermedades cardiovasculares / Estimation of lifetime risk of cardiovascular disease (IBERLIFERISK): a new tool for cardiovascular disease prevention in primary care

Introducción y objetivos: Desarrollar una función predictiva del riesgo cardiovascular de por vida de eventos cardiovasculares, mortales y no mortales en población laboral española. Métodos: Estudio de cohortes retrospectivo. Se seleccionó a trabajadores de entre 18 y 65 años sin antecedentes de enfermedad cardiovascular que realizaron un examen de salud entre los años 2004 y 2007. El 70% de la cohorte se utilizó para desarrollar la ecuación de riesgo y el 30%, para validar la ecuación. Se construyeron 4 modelos de riesgos proporcionales de Cox en los que se utilizaron como variables dependientes la aparición de eventos cardiovasculares y la aparición de eventos competitivos; se usaron los mismos modelos en varones y mujeres. Los eventos mortales y no mortales se evaluaron hasta el año 2014. Resultados: Se incluyó a 762.054 sujetos, con una media de edad de 35,48 años (el 71,14% varones). Resultaron factores significativos en el modelo la ocupación manual, el tabaquismo, la diabetes mellitus, el tratamiento antihipertensivo, la presión arterial sistólica, el colesterol total, el colesterol unido a lipoproteínas de alta densidad y el tratamiento hipolipemiante; en varones, el consumo de alcohol, el índice de masa corporal, los antecedentes de enfermedad coronaria precoz en familiares de primer grado, la enfermedad renal y la presión arterial diastólica. El área bajo la curva c fue 0,84 (IC95%, 0,82-0,85) en varones y 0,73 (IC95%, 0,66-0,80) en mujeres. La calibración mostró una subestimación en los deciles de bajo riesgo y sobrestimación en los de alto riesgo. Conclusiones: El modelo de riesgo cardiovascular de por vida tiene una discriminación y una calibración satisfactorias, con mejores resultados para varones que para mujeres

Introduction and objectives: To develop a predictive function of lifetime cardiovascular risk, including morbidity and mortality, in a healthy working population in Spain. Methods: Retrospective cohort study. We selected healthy workers, aged 18 to 65 years, with no history of cardiovascular disease, who underwent a health assessment between 2004 and 2007. We used 70% of the cohort to develop the risk equation, and the remaining 30% to validate the equation. Four Cox proportional hazards models were constructed using cardiovascular events and competing events as dependent variables. The same models were replicated for men and women separately. Fatal and nonfatal events were assessed until 2014. Results: A total of 762 054 individuals were selected. The mean age was 35.48 years and 71.14% were men. Significant risk variables in the model included manual occupations, being a smoker or exsmoker, diabetes mellitus, antihypertensive treatment, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and lipid-lowering treatment; in men, the model also included alcohol consumption, body mass index, a family history of early coronary disease in first-degree relatives, renal failure, and diastolic blood pressure. The area under the curve receiver operating characteristic was 0.84 (95%CI, 0.82-0.85) in men and 0.73 (95%CI, 0.66-0.80) in women. Calibration showed underestimation in low-risk deciles and overestimation in high-risk deciles. Conclusions: The new lifetime cardiovascular risk model has satisfactory discrimination and calibration, with better results in men than in women

Considerations for clinical curation, classification, and reporting of low-penetrance and low effect size variants associated with disease risk.

PURPOSE: Clinically relevant variants exhibit a wide range of penetrance. Medical practice has traditionally focused on highly penetrant variants with large effect sizes and, consequently, classification and clinical reporting frameworks are tailored to that variant type. At the other end of the penetrance spectrum, where variants are often referred to as "risk alleles," traditional frameworks are no longer appropriate. This has led to inconsistency in how such variants are interpreted and classified. Here, we describe a conceptual framework to begin addressing this gap. METHODS: We used a set of risk alleles to define data elements that can characterize the validity of reported disease associations. We assigned weight to these data elements and established classification categories expressing confidence levels. This framework was then expanded to develop criteria for inclusion of risk alleles on clinical reports. RESULTS: Foundational data elements include cohort size, quality of phenotyping, statistical significance, and replication of results. Criteria for determining inclusion of risk alleles on clinical reports include presence of clinical management guidelines, effect size, severity of the associated phenotype, and effectiveness of intervention. CONCLUSION: This framework represents an approach for classifying risk alleles and can serve as a foundation to catalyze community efforts for refinement.

MDGC-MS analysis of essential oils from Protium heptaphyllum (Aubl. ) and their antifungal activity against Candida specie / Análise MDGC-MS de óleos essenciais de Protium heptaphyllum (Aubl. ) e sua atividade antifúngica contra espécies de Candida

ABSTRACT Protium heptaphyllum is found in the Amazon region, and in various Brazilian states and South American countries. Also Known as almecega, it produces an oil resin used in traditional medicine as analgesic, anti-inflammatory, cicatrizant and expectorant, it is rich in pentacyclic triterpenes and essential oil. The main objective of this study was to analyze the chemical composition of P. heptaphyllumresin (OEPh) over different extraction times and to evaluate their antifungal activity against Candida species, obtained from gardeners with onychomycosis, using the disk diffusion method. The OEPh was obtained by hydrodistillation and analyzed by Multidimensional Gas Chromatography coupled with Mass Spectrometry (MDGC / MS). Candida species were obtained from lesions on the nails of horticulturist from a community garden in the city of Teresina, Piauí, Brazil. The antifungal activity in concentrations of 1000 µg/L, 500 µg/L and 250 µg/L, PROTOCOL M44-A2 (CLSI 2009) OEPh was tested. The main constituents identified were: l-limonene, α-terpineol, p-cineol, o-cymene and α-phellandrene, however, its composition varies significantly with extraction time. All species, except C. rugosa, were inhibited with halo (≥ 14 mm) at 1000 μg / L. C. krusei is naturally resistant to the drug fluconazole, but when tested with OEPh the clinical species (case 9) demonstrated sensitivity in three dilutions (halo ≤ 10 ≥ 14) and the standard strain was inhibited at concentration of 1000 μg/Lg / L (halo 14mm). A similar situation also occurred with the standard strain of C. parapsilosis (halo ≥ 11mm). OEPh has considerable antifungal activity, which merits further investigation for alternative clinical applications, since this species is widely distributed in our community, and it presents good yields, and also has important therapeutic applications.

RESUMO Protium heptaphyllum é encontrada na região amazônica, em vários estados do Brasil e países da América do Sul. Conhecida como almecega produz uma resina oleosa usada na medicina popular como analgésica, antiinflamatória, cicatrizante e expectorante, é rica em triterpenos pentaciclicos e óleo essencial. O objetivo principal do presente trabalho foi analisar a composição química do óleo essencial da resina P. heptaphyllum (OEPh) em diferentes tempo de extração e avaliarsuaatividade antifúngica contra espécies de Candida, isoladas de horticultores com onicomicoses, por método de disco-difusão. O OEPh foi obtido por hidrodestilação, analisado por Cromatografia Gasosa Multidimensinal Acoplada a Espectrometria de Massas (MDGC/MS). As espécies de Candida foram obtidas de lesões nas unhas de horticultores de uma horta comunitária na cidade de Teresina, Piauí, Brasil. Testou-se a atividade antifúngica do OEPhnas concentrações de 1000 μg/L, 500 μg/L e 250 μg/L, protocolo M44-A2 (CLSI 2009). Os principais constituintes identificados foram l- limoneno, α-terpineol, p-cineol, o-cimeno e α-felandreno, entretanto, sua composição varia significativamente em decorrência do tempo de extração. Todas as espécies, exceto a C. rugosa, foram inibidas com halo ( Χ ≥ 14 mm) na concentração de 1000 μg/L. C. krusei é naturalmente resistente ao fármaco fluconazol, mas quando testado com OEPh,a espécie clínico (caso 9) demonstrou sensibilidade nas três diluições (halo Χ ≤ 10 ≥ 14) e a cepa padrão foi inibida na concentração de 1000 μg/L (halo Χ 14mm). Fato semelhante também ocorreu com a cepa padrão de C. parapsilosis (halo Χ ≥ 11mm). O OEPh possui atividade antifúngica considerável, merecendo uma investigação mais aprofundada para aplicações clínicas alternativas, uma vez que esta espécie é amplamente distribuída em nossa comunidade, apresenta bom rendimento e, ainda, aplicações terapêuticas importantes.

Multivariate pattern classification reveals differential brain activation during emotional processing in individuals with psychosis proneness.

Among the general population, individuals with subthreshold psychotic-like experiences, or psychosis proneness (PP), can be psychometrically identified and are thought to have a 10-fold increased risk of psychosis. They also show impairments in measures of emotional functioning parallel to schizophrenia. Whilst previous studies have revealed altered brain activation in patients with schizophrenia during emotional processing, it is unclear whether these alterations are also expressed in individuals with high PP. Here we used Support Vector Machine (SVM) to perform multivariate pattern classification based on brain activation during emotional processing in 20 individuals with high PP and 20 comparison subjects (low PP). In addition, we performed a standard univariate analysis based on the General Linear Model (GLM) on the same data for comparison. The experimental task involved passively viewing negative and neutral pictures from the International Affective Picture System (IAPS). SVM allowed classification of the two groups with statistically significant accuracy (p=0.017) and identified group differences within an emotional circuitry including the amygdala, insula, anterior cingulate and medial prefrontal cortex. In contrast, the standard univariate analysis did not detect any significant between-group differences. Our results reveal a distributed and subtle set of alterations in brain function within the emotional circuitry of individuals with high PP, providing neurobiological support for the notion of dysfunctional emotional circuitry in this group. In addition, these alterations are best detected using a multivariate approach rather than standard univariate methods. Further application of this approach may aid in characterising people at clinical and genetic risk of developing psychosis.

Gender-specific differences in effects of prenatal and postnatal environmental tobacco smoke exposure on respiratory symptoms in 23,474 children with and without allergic predisposition: results from 25 districts of northeast China.

To assess the interaction of environmental tobacco smoke (ETS) exposure and allergic predisposition regarding respiratory health among Chinese children, a sample of 23,474 children (6-13 years old) was studied from 25 districts in Liaoning province, China. The results showed that children without allergic predisposition were more susceptible to ETS than children with allergic predisposition. Among children without allergic predisposition, ETS exposure was associated with more respiratory symptoms and diseases in boys than in girls; In utero ETS exposure was associated with history of asthma (OR, 1.86; 95% CI, 1.44-2.40) and current asthma (OR, 2.25; 95% CI, 1.48-3.44) only among boys without allergic predisposition. Among children with allergic predisposition, more associations between ETS exposure and respiratory symptoms and diseases were detected in girls. In conclusion, ETS exposure was more evident in boys without family atopy history and more associations were detected in girls with family atopy history.

Proof of principle: the predisposition, infection, response, organ failure sepsis staging system.

OBJECTIVE: In an effort to improve upon the traditional sepsis syndrome definitions, the predisposition, infection, response, organ dysfunction (PIRO) model was proposed to better characterize sepsis. The objective of this investigation was to derive and validate a sepsis staging system based on the PIRO concept that risk stratifies patients with suspected infection. DESIGN: Three independent, observational, prospective cohorts were studied. A derivation cohort (n = 2,132) was used to create the PIRO score, identifying independent predictors of mortality. Individual values were assigned to create the weighted integer score for each parameter, yielding the final PIRO score. The prognostic performance was then investigated in independent internal (n = 4,618) and external (n = 1,004) validation cohorts. SETTING: Two large U.S. tertiary care centers. PATIENTS: Patients admitted to the hospital from the emergency department with suspected infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The PIRO staging system was created by combining components of predisposition (age, chronic obstructive pulmonary disease, liver disease, nursing home residency, and malignancy with and without metastasis), infection (pneumonia and cellulitis), response (tachypnea, bandemia, and tachycardia), and organ dysfunction (renal, respiratory, cardiac, metabolic, and hematologic). The derived PIRO score showed stepwise increase in mortality with increasing points and high discriminatory ability with an area under the curve of 0.90 in the derivation cohort, 0.86 in internal validation, and 0.83 in external validation. CONCLUSIONS: This study provides evidence-based support for the PIRO approach to sepsis staging. Future efforts may utilize this approach with additional parameters (e.g., genetics and novel biochemical markers) to develop further the PIRO stratification system.

Objective determination of Fitzpatrick skin type.

The overall aim of this Ph.D. project was to clarify what the subjective Fitzpatrick skin type represents with regard to the skin's reaction to UVR. Fitzpatrick skin type is used as an expression of the constitutive UV-sensitivity. It has been used for guiding dose-levels in phototherapy and is an important risk factor for skin cancer. The subjective Fitzpatrick skin type and the measured skin type PPF (pigment protection factor, calculated based on a skin reflectance measurement, predicts the UV-dose (SED) to give 1 MED) were investigated parallelly in relation to the clinically determined dose to erythema (MED) and/or pigmentation (MMD) to determine which one related best. PPF is an established method for assessing UV-sensitivity by predicting SED to MED. UV-dose to MED and/or MMD was determined after single UV-exposure to Solar Simulator on nates (n= 84) and after single and multiple (5, 6 or 12) UV-exposures (n = 24-62) on the back to four UV-sources (nUVB, Solar, bUVA and UVA1). SED to MMD was also related to wavelength. MED was only determined after a single and four UV-exposures to narrowband UVB (nUVB) and Solar Simulator (Solar). Volunteers with a broad range of constitutive pigmentation (skin types I-V) were included. Equal MMD doses (predetermined after a single UV-exposure) were used at the multiple exposures. The absolute increase in pigmentation after 6 and 12 UV-exposures, where steady-state pigmentation was reached, was independent of skin type and therefore could not enter into the calculations. But it proved that the MMD determinations after single exposure were correct and could be used at multiple UV-exposures. In contrary to what we expected, our results indicate that people may refer to the constitutive pigmentation, when they reply to the question of Fitzpatrick skin type. This applied to both erythema and pigmentation response as both dose to MED and MMD showed a better correlation to nates than to the back. As expected, our results from the back indicate that people seem to refer to sun sensitivity after multiple exposures to the sun rather than a single sun exposure, when they reply to the question of Fitzpatrick skin type. Hence, both SED to MED and SED to MMD are better correlated to skin type after respectively 4 and 5 exposures to Solar Simulator and nUVB compared to 1 exposure. Only when tanning is preceded by erythema there is a relation between SED to MMD and skin type/PPF. Thus only after nUVB and Solar. For nUVB and Solar there was a linear relation between erythema and tanning ability with the intercept different from zero. In spite of what we expected based on the literature, the correlation was better between SED to MED and skin type than between SED to MMD and skin type. This applied to single and multiple exposures and to single calculations and multiple regression analyses. The long-waved UVA1 and broadband UVA should definitely not be used for skin type determination, as there was no relation between MMD and skin type/PPF. Both nUVB and Solar can be considered. Finally, based on the objective parameters: pre-exposure pigmentation measured by skin reflectance, MED and MMD we tried to predict the Fitzpatrick skin type by multinominal logistic regression analyses to evaluate the significance of the different parameters for the subjective skin type classification and thereby hopefully enlighten what Fitzpatrick skin type represents. For single UV-exposure only the pre-exposure pigmentation worked as a predictor of Fitzpatrick skin type, and that is what PPF is based on. When this parameter was removed, only SED to MED was significant. Our model succeeds better to classify people correct after multiple UV-exposure compared to a single UV-exposure. PPF was predicted likewise and was highly correlated to SED to MED, as expected, and even higher correlated to Fitzpatrick skin type. SED to MMD was not significant. This study confirms that Fitzpatrick skin type is an unreliable predictor of UV-sensitivity with regard to MED- and MMD test. Fitzpatrick skin type in epidemiological context (risk for skin cancer) stands for burns and ability to tan may represent "cumulative" dose. SED to MED is equivalent to burns. PPF may also indirectly represent cumulative dose--the less pigmented the skin the more UVR penetrates the epidermis and will be able to accumulate and induce skin cancer. Our results indicate that Fitzpatrick skin type predominantly is determined by the skin pigmentation and that the second most important objective parameter is SED to MED (and not SED to MMD). This explains why Fitzpatrick skin type, eventhough being an unreliable predictor of UV-sensitivity, still plays an important role in epidemiology with regard to estimation of risk of skin cancer. This study showed that PPF can predict the UV-sensitivity also with regard to the tanning ability (MMD), can be applied to multiple UV-exposures and to a broader pigmentation spectrum. PPF is preferred to predict the individual UV-sensitivity rather than the subjective Fitzpatrick skin type, confirmed for both nates and back, single as well as repetitive UV-exposures. It should therefore be considered to concentrate on skin reflectance measurements.

A risk factor study of coccidioidomycosis by controlling differential misclassifications of exposure and susceptibility using a landscape ecology approach.

State-reported coccidioidomycosis cases in Arizona have dramatically increased since 1997, raising concerns about a possible epidemic, its cause, and associated risk factors, including spatio-temporal differences in susceptibility and exposure. This stratified, two-stage, cross-sectional study evaluates inherent, socio-economic, and environmental risk factors of coccidioidomycosis from information collected during an address-based telephone survey of 5460 households containing 14,105 individuals in greater Tucson, Arizona. Three geomorphic and two demographic strata controlled for differences in group-level exposures and susceptibility, and assured recruitment of a minority population. Logistic regression of self-reported cases indicates that location of residence by geomorphic and demographic strata was a risk factor that confounded the associations of coccidioidomycosis with age, race-ethnicity, and educational attainment. The risk due to age is more evenly distributed across the population than bivariate results when individual- and group-level exposure and susceptibility factors are controlled. Similarly the association for being Hispanic decreased from strong bivariate 0.28 odds ratio to a weak multivariate 0.75. Location of residence confounded the risk due to race-ethnicity and was an effect modifier of risk due to age. Differential misclassification of exposure to Coccidioides spores and susceptibility to coccidioidomycosis was reduced through landscape stratification by demographics and geomorphic types. Landscape epidemiological studies of diseases with strong environmental and demographic determinants can reduce residual confounding and account for spatial and temporal differences between neighborhoods and at broader scales.

Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non-Hodgkin's lymphoma: the ESCALE study (SFCE).

The role of a family history of cancer in the etiology of childhood hematopoietic malignancies was investigated using the data from the ESCALE study. ESCALE, a population-based case-control study, was carried out in France over the period, 2003-2004. A total of 773 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma (HL), 163 of non-Hodgkin's lymphoma (NHL) and 1,681 population-based controls were included. The controls were randomly selected from the French population and were frequency matched with the cases on age and gender. Cancer history in first- and second-degree relatives was reported by the mothers in a structured telephone questionnaire that was the same for the cases and controls. Odds ratios (ORs) were estimated using an unconditional regression model taking into account the stratification variables and potential confounders. A family history of cancer was associated with an increased risk of HL (OR = 1.5 [1.0-2.2]) and NHL (OR = 1.8 [1.3-2.5]), but not AL (OR = 1.0 [0.9-1.2]). The ORs were higher when at least 2 relatives had a history of cancer or when 1 case occurred before age 46 years. Only HL was significantly associated with a family history of hematopoietic malignancies (OR = 2.0 [1.0-3.8]), mainly because of a significant association with a history of HL (OR = 5.4 [1.3-22]). In conclusion, the study findings support the hypothesis of familial susceptibility to childhood lymphoma, but do not suggest familial susceptibility to childhood AL.

Circulating adhesion molecules in apoE-deficient mouse strains with different atherosclerosis susceptibility.

Recruitment of inflammatory cells in the arterial wall by vascular adhesion molecules plays a key role in development of atherosclerosis. Apolipoprotein E-deficient (apoE(-/-)) mice have spontaneous hyperlipidemia and develop all phases of atherosclerotic lesions. We sought to examine plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and sP-selectin in two apoE(-/-) strains C57BL/6 (B6) and BALB/c with early or advanced lesions. Mice were fed chow or a Western diet containing 42% fat, 0.15% cholesterol, and 19.5% casein. On either diet, BALB/c.apoE(-/-) mice developed much smaller atherosclerotic lesions and displayed significantly lower levels of sVCAM-1 and sP-selectin than B6.apoE(-/-) mice. The Western diet significantly elevated sVCAM-1 levels in both strains and sP-selectin levels in B6.apoE(-/-) mice. BALB/c.apoE(-/-) mice exhibited 2-fold higher HDL cholesterol levels on the chow diet and 15-fold higher HDL levels on the Western diet than B6.apoE(-/-) mice, although the two strains had comparable levels of total cholesterol and triglyceride. Thus, increased atherosclerosis is accompanied by increases in circulating VCAM-1 and P-selectin levels in the two apoE(-/-) mouse strains, and the high HDL level may protect against atherosclerosis by inhibiting the expression of adhesion molecules in BALB/c.apoE(-/-) mice.

Perceived breast cancer risk: heuristic reasoning and search for a dominance structure.

Studies suggest that people construct their risk perceptions by using inferential rules called heuristics. The purpose of this study was to identify heuristics that influence perceived breast cancer risk. We examined 11 interviews from women of diverse ethnic/cultural backgrounds who were recruited from community settings. Narratives in which women elaborated about their own breast cancer risk were analyzed with Argument and Heuristic Reasoning Analysis methodology, which is based on applied logic. The availability, simulation, representativeness, affect, and perceived control heuristics, and search for a dominance structure were commonly used for making risk assessments. Risk assessments were based on experiences with an abnormal breast symptom, experiences with affected family members and friends, beliefs about living a healthy lifestyle, and trust in health providers. Assessment of the potential threat of a breast symptom was facilitated by the search for a dominance structure. Experiences with family members and friends were incorporated into risk assessments through the availability, simulation, representativeness, and affect heuristics. Mistrust in health providers led to an inappropriate dependence on the perceived control heuristic. Identified heuristics appear to create predictable biases and suggest that perceived breast cancer risk is based on common cognitive patterns.

Distinguishing genetic disease and genetic susceptibility.

With the increasing awareness of the involvement of genetic factors in disease, questions arise as to what distinguishes genetic from non-genetic disease, and what constitutes a genetic susceptibility. A general framework, reflecting the structure of biological explanations, is presented in which such distinctions can be made. We conclude that such distinctions are objective and are based on the biological facts; they are not "social constructions" nor do they presuppose resolution of philosophical problems regarding causation.

Suscetibilidade de Biomphalaria tenagophila e Biomphalaria glabrata de uma mesma regiao a duas cepas de Schistosoma mansoni / Susceptibility of Biomphalaria tenagophila and Biomphalaria glabrata from the same region to two brazilian strains of Schistoma mansoni

Em testes de suscetibilidade, a B. tenagophila (Ouro Branco - MG) mostrou-se positiva a partir da terceira geracao mantida em laboratorio para a cepa SJ de S. mansoni, em dois testes separados. Usando-se um "pool" de miracidios para as infeccoes em massa as taxas de positividade foram 5 por cento e 10 por cento, enquanto que para a cepa LE a taxa foi de 1 por cento. Com exemplares da terceira geracao expostos individualmente a 10 miracidios, a taxa de positividade de B. tenagophila (OB, MG) foi de 2 por cento para a cepa LE.AB. glabrata (Gage - MG), apresentou, em um unico teste, 58 por cento de positividade para a cepa LE, em condicoes laboratoriais. como controle para as infeccoes com a cepa SJ foi utilizado a B. tenagophila da Cabo Frio, RJ, que apresentou positividade de 47 a 85 por cento e a B. glabrata (BH) que apresentou positividade de 40 a 75 por cento.