The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Light-independent degradation of stromal proteins in intact chloroplasts isolated from Pisum sativum L. leaves: requirement for divalent cations

Intact chloroplasts were isolated from mature pea (Pisum sativum L.) leaves in order to study the degradation of several stromal proteins in organello. Changes in the abundances of ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39), phosphoribulokinase (EC 2.7.1.19), glutamine synthetase (EC 6.3.1.2) and ferredoxin-dependent glutamine:α-ketoglutarate aminotransferase (glutamate synthase; EC 1.4.7.1) were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Coomassie-staining of the gels or immunoblotting using specific antibodies for the different enzymes. Degradation of several stromal proteins was strongly stimulated when intact chloroplasts were incubated in the light in the presence of dithiothreitol. Since free radicals may artificially accumulate in the chloroplast under such conditions and interfere with the stability of stromal proteins, the general relevance of these processes remains questionable. In the absence of light, proteolysis proceeded slowly in isolated chloroplasts and was not stimulated by dithiothreitol. Inhibition by ethylenediaminetetraacetic acid (EDTA), 1,10-phenanthroline or excess zinc ions as well as the requirement for divalent cations suggested that a zinc-containing metalloprotease participated in this process. Furthermore, light-independent degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase and phosphoribulokinase was enhanced in chloroplasts isolated from leaves in which senescence was accelerated by nitrogen starvation. Our results indicate that light-independent stromal protein degradation in intact chloroplasts may be analogous to proteolysis that occurs in intact leaves during senescence.

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study.

OBJECTIVE To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). DESIGN Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. METHODS Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. RESULTS In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. CONCLUSIONS Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

Evidence of secondary dengue infection and potential for association with clinical depression in a subset of a randomly selected cohort in South Texas

Globally, dengue is an emerging disease resulting in an estimated 50 million new cases and 22, 000 deaths each year. Anecdotally, depression has been reported as a possible sequelae of dengue virus infection. To test the association, we performed a cross-sectional analysis in a selected sub-set of participants from the Cameron County Hispanic Cohort (CCHC) in South Texas. All study subjects in the analysis had Center for Epidemiological Studies Depression scale (CES-D) scores and were tested for dengue antibodies using stored plasma. We found that 5.0% of participants tested either positive or equivocal for anti-dengue IgG antibodies using the capture antibody test, which detects acute secondary infections. Logistic regression identified that evidence of acute secondary dengue infection was not associated with depression (Odds Ratio [OR] = 0.97, 95%Confidence Interval [CI] 0.47-1.98); however, both being female (OR = 1.53, 95%CI 1.09-2.15) and obese body mass index (BMI > 30) (OR = 1.84, 95%CI 1.19-2.84) were associated with depression. ^

Factors associated with hospital admission of elder cardiovascular patients in an emergency center

Context. Healthcare utilization of elder cardiovascular patients in United States will increase in near future, due to an aging population. This trend could burden urban emergency centers, which have become a source of primary care. ^ Objective. The objective of this study was to determine the association of age, gender, ethnicity, insurance and other presenting variables on hospital admission in an emergency center for elder cardiovascular patients. ^ Design, setting and participants. An anonymous retrospective review of emergency center patient login records of an urban emergency center in the years 2004 and 2005 was conducted. Elder patients (age ≥ 65 years) with cardiovascular disease (ICD91 390-459) were included. Multivariate logistic regression analysis was used to identify independent factors for hospital admission. Four major cardiovascular reasons for hospitalisation – ischemic heart disease, heart failure, hypertensive disorders and stroke were analysed separately. ^ Results. The number of elder patients in the emergency center is increasing, the most common reason for their visit was hypertension. Majority (59%) of the 12,306 elder patients were female. Forty five percent were uninsured and 1,973 patients had cardiovascular disease. Older age (OR 1.10; CI 1.02-1.19) was associated with a marginal increase in hospital admission in elder stroke patients. Elder females compared to elder males were more likely to be hospitalised for ischemic heart disease (OR 2.71; CI 1.22-6.00) and heart failure (OR 1.58; CI 1.001-2.52). Furthermore, insured elder heart failure patients (OR 0.54; CI 0.31-0.93) and elder African American heart failure patients (OR 0.32; CI 0.13-0.75) were less likely to be hospitalised. Ambulance use was associated with greater hospital admissions in elder cardiovascular patients studied, except for stroke. ^ Conclusion. Appropriate health care distribution policies are needed for elder patients, particularly elder females, uninsured, and racial/ethnic minorities. These findings could help triage nurse evaluations in emergency centers to identify patients who were more likely to be hospitalised to offer urgent care and schedule appointments in primary care clinics. In addition, health care plans could be formulated to improve elder primary care, decrease overcrowding in emergency centers, and decrease elder healthcare costs in the future. ^

Case-control study of factors associated with virologic failure in HIV-infected children on HAART in Botswana, a developing African country

According to the United Nations Program on HIV/AIDS (UNAIDS, 2008), in 2007 about 67 per cent of all HIV-infected patients in the world were in Sub-Saharan Africa, with 35% of new infections and 38% of the AIDS deaths occurring in Southern Africa. Globally, the number of children younger than 15 years of age infected with HIV increased from 1.6 million in 2001 to 2.0 million in 2007 and almost 90% of these were in Sub-Saharan Africa. (UNAIDS, 2008).^ Both clinical and laboratory monitoring of children on Highly Active Anti-Retroviral Therapy (HAART) are important and necessary to optimize outcomes. Laboratory monitoring of HIV viral load and genotype resistance testing, which are important in patient follow-up to optimize treatment success, are both generally expensive and beyond the healthcare budgets of most developing countries. This is especially true for the impoverished Sub-Saharan African nations. It is therefore important to identify those factors that are associated with virologic failure in HIV-infected Sub-Saharan African children. This will inform practitioners in these countries so that they can predict which patients are more likely to develop virologic failure and therefore target the limited laboratory monitoring budgets towards these at-risk patients. The objective of this study was to examine those factors that are associated with virologic failure in HIV-infected children taking Highly Active Anti-retroviral Therapy in Botswana, a developing Sub-Saharan African country. We examined these factors in a Case-Control study using medical records of HIV-infected children and adolescents on HAART at the Botswana-Baylor Children's Clinical Center of Excellence (BBCCCOE) in Gaborone, Botswana. Univariate and Multivariate Regression Analyses were performed to identify predictors of virologic failure in these children.^ The study population comprised of 197 cases (those with virologic failure) and 544 controls (those with virologic success) with ages ranging from 3 months to 16 years at baseline. Poor adherence (pill count <95% on at least 3 consecutive occasions) was the strongest independent predictor of virologic failure (adjusted OR = 269.97, 95% CI = 104.13 to 699.92; P < 0.001). Other independent predictors of virologic failure identified were: First Line NNRTI with Nevirapine (OR = 2.99, 95% CI = 1.19 to7.54; P = 0.020), Baseline HIV-1 Viral Load >750,000/ml (OR = 257, 95% CI = 1.47 to 8.63; P = 0.005), Positive History of PMTCT (OR = 11.65, 95% CI = 3.04-44.57; P < 0.001), Multiple Care-givers (>=3) (OR = 2.56, 95% CI = 1.06 to 6.19; P = 0.036) and Residence in a Village (OR = 2.85, 95% CI = 1.36 to 5.97; P = 0.005).^ The results of this study may help to improve virologic outcomes and reduce the costs of caring for HIV-infected children in resource-limited settings. ^ Keywords: Virologic Failure, Highly Active Anti-Retroviral Therapy, Sub-Saharan Africa, Children, Adherence.^

Early stage breast cancer and comorbidities: Their impact on breast cancer disease-free survival differences by ethnicity

The retrospective cohort study examined the association between the presence of comorbidities and breast cancer disease-free survival rates among racial/ethnic groups. The study population consisted of 2389 women with stage I and II invasive breast cancer who were diagnosed and treated at the M.D. Anderson Cancer Center between 1985 and 2000. It has been suggested that as the number of comorbidities increases, breast cancer mortality increases. It is known that African Americans and Hispanics are considered to be at a higher risk for comorbid conditions such as hypertension and diabetes compared to Caucasian women (23) (10). When compared to Caucasian women, African American women also have a higher breast cancer mortality rate (1). As a result, the study also examined whether comorbid conditions contribute to racial differences in breast cancer disease-free survival. Among the study population, 24% suffered from breast cancer recurrence, 6% died from breast cancer and 24% died from all causes. The mean age was 56 with 41% of the population being women between the ages of 40-55. One or more comorbidities were reported in 84 (36%) African Americans (OR 1.57; 95% CI 1.19-2.10), 58 (31%) Hispanics (OR 1.25; 95% CI 0.90-1.74) compared to the reference group of 531 (27%) Caucasians. Additionally, African American women were significantly more likely to suffer from either a breast cancer recurrence or breast cancer death (OR 1.5; 95% CI 0.70-1.41) when compared to Caucasian women. Multivariate analysis found hypertension (HR 1.22; 95% CI 0.99-1.49; p<0.05) to be statistically significant and a potential prognostic tool for disease-free survival with African American women (OR 2.96; 95% 2.25-3.90) more likely to suffer from hypertension when compared to Caucasian women. When compared to Caucasian women, Hispanics were also more likely to suffer from hypertension (OR 1.33; 95% CI 0.96-1.83). This suggests that comorbid conditions like hypertension could account for the racial disparities that exist when comparing breast cancer survival rates. Future studies should investigate this relationship further.^

Estrogen-induced gene expression and patient survival in high-grade serous carcinoma of the ovary

Background. Assessment of estrogen receptor (ER) expression has inconsistent utility as a prognostic marker in epithelial ovarian carcinoma. In breast and endometrial cancers, the use of estrogen-induced gene panels, rather than ER expression alone, has shown improved prognostic capability. Specifically, over-expression of estrogen-induced genes in these tumors is associated with a better prognosis and signifies estrogen sensitivity that can be exploited with hormone antagonizing agents. It was therefore hypothesized that estrogen-induced gene expression in ovarian carcinoma would successfully predict outcomes and differentiate between tumors of varying estrogen sensitivities. Methods. Two hundred nineteen (219) patients with ovarian cancer who underwent surgery at M. D. Anderson between 2004 and 2007 were identified. Of these, eighty-three (83) patients were selected for inclusion because they had advanced stage, high-grade serous carcinoma of the ovary or peritoneum, had not received neoadjuvant chemotherapy, and had readily available frozen tissue for study. All patients had also received adjuvant treatment with platinum and taxane agents. The expression of seven genes known to be induced by estrogen in the female reproductive tract (EIG121, sFRP1, sFRP4, RALDH2, PR, IGF-1, and ER) was measured using qRT-PCR. Unsupervised cluster analyses of multiple gene permutations were used to categorize patients as high or low estrogen-induced gene expressors. QPCR gene expression results were then compared to ER and PR immunohistochemical (IHC) expression. Cox proportional hazards models were used to evaluate the effects of both individual genes and selected gene clusters on patient survival. Results. Median follow-up time was 38.7 months (range 1-68 months). In a multivariate model, overall survival was predicted by sFRP1 expression (HR 1.10 [1.02-1.19], p=0.01) and EIG121 expression (HR 1.28 [1.10-1.49], p<0.01). A cluster defined by EIG121 and ER was further examined because that combination appeared to reasonably segregate tumors into distinct groups of high and low estrogen-induced gene expressors. Shorter overall survival was associated with high estrogen-induced gene expressors (HR 2.84 [1.11-7.30], p=0.03), even after adjustment for race, age, body mass index, and residual disease at debulking. No difference in IHC ER or PR expression was noted between gene clusters. Conclusion. In sharp contrast to breast and endometrial cancers, high estrogen-induced gene expression predicts shorter overall survival in patients with high-grade serous ovarian carcinoma. An estrogen-induced gene biomarker panel may have utility as prognostic indicator and may be useful to guide management with estrogen antagonists in this population.^

Low birthweight and the risk of developing subsequent high blood pressure and/or dyslipidemia in childhood

The association between birthweight and blood pressure (BP), and birthweight and serum lipid concentrations at age 7 through 11 years was examined in 1446 black and white children. The prevalence ratio (with 95% confidence interval) for being in the race-, sex- and age-specific upper decile of diastolic BP in children born with low birthweight (LBW, $<$2500 grams) versus children with birthweight $\geq$2500 grams was for black boys, 2.66 (1.24-5.70). In the other race-sex groups for diastolic BP, and in all race-sex groups for systolic BP this ratio did not differ from one. Among white boys with LBW, but not in the other race-sex groups, higher than expected percentages of subjects were in the highest decile group of triglyceride concentrations (0.01 $<$ p $<$ 0.05). The prevalence ratio was 2.42 (1.19-4.91). When prematures were excluded only more than expected white girls with LBW were in the highest decile group of triglyceride concentrations. The prevalence ratio was 3.23 (1.16-9.00). Prevalence ratios for triglyceride concentrations in black boys and girls, and for LDL/HDL-C ratio, cholesterol and VLDL-C concentrations in all race-sex groups were not different from one in analyses including and in those excluding prematures. Mean triglyceride concentrations stratified by tertiles of Quetelet Index, race and sex showed a strongly positive association between triglyceride concentrations and Quetelet Index, and in the upper tertile of the Quetelet Index an association between LBW and raised triglyceride concentrations. Multiple linear regression analyses showed that after adjusting for sex, race and age present Quetelet Index (p $<$ 0.001) is a much stronger predictor of systolic and diastolic BP, and also of LDL-C/HDL-C ratio and triglyceride concentrations in this age group than birthweight (p $>$ 0.05). Thus, an association between LBW and subsequent risk for elevated BP was confirmed for diastolic BP in black boys, but not for the other race-sex groups, and not for systolic BP in any group. This is the first study finding an association between LBW and elevated triglyceride concentrations in boys (white and black) and girls (white). A follow-up study to assess whether the findings can be confirmed at adult age is recommended. ^

Evaluación del rendimiento y calidad de cultivares de ajo colorado fertirrigados con nitrógeno

El objetivo de este trabajo fue diferenciar cultivares monoclonales de ajos colorados argentinos por sus características productivas, de calidad y respuesta a la fertilización nitrogenada en la región de Cuyo. Durante la campaña 2003 se realizó un ensayo en La Consulta, San Carlos, Mendoza, Argentina (950 msnm; 33° 42' S y 69° 04' W). El diseño experimental fue en franjas con parcelas divididas dispuestas en un diseño de bloques completos al azar de tres repeticiones en el cual las dosis de nitrógeno (75, 150, 225 y 300 kg de N·ha-1) incorporadas como SolUAN (30 % N) se asignaron a las parcelas principales y las subparcelas correspondieron a cinco clones de ajo: Fuego INTA, Sureño INTA, Gostoso INTA, Inco 30 y Rubí INTA. Se adicionó además un tratamiento control sin nitrógeno. En el análisis estadístico de los rendimientos (r2 = 0,81; cv%: 8,48 y p < 0,0001) se detectaron efectos significativos de las variables cultivares y dosis de fertilización nitrogenada pero no de la interacción de ambas. Se determinó que en suelos con contenidos medios de nitrógeno total (800 mg·kg-1), la dosis que maximiza los rendimientos es de 150 kg N·ha-1 en todas las cultivares salvo Gostoso cuyo valor crítico resultó mayor que el resto. El incremento de rendimiento atribuible a la fertirrigación con 150 kg N·ha-1 respecto del testigo fue: 45 % en Rubí (17,7 t· ha-1), 31 % en Fuego (15,3 t·ha-1), 19 % en Inco (15,4 t·ha-1) y 23 % en Sureño (13 t·ha-1). Gostoso aumentó un 21 % (13,8 t·ha-1) su rendimiento respecto del testigo con la dosis de 300 kg N·ha-1. El análisis de clasificación jerárquica permitió agrupar los genotipos según su potencial productivo, de mayor a menor, en tres clases: I: cv. Rubí ; II: cv. Inco 30 y cv. Fuego; III: cv. Sureño y Gostoso. La fertilización nitrogenada incrementó la manifestación de malformaciones en todas las cultivares respecto del testigo sin fertilización, excepto Sureño que presentó mayores anormalidades en el tratamiento testigo sin fertilizar.

Mineralogy of altered whole rocks from ODP Sites 193-1188 and 193-1189, PACMANUS field

Postcruise X-ray diffraction (XRD) data for 95 whole-rock samples from Holes 1188A, 1188F, 1189A, and 1189B are presented. The samples represent alteration types recovered during Leg 193. The data set is incorporated into the shipboard XRD data set. Based on the newly obtained XRD data, distribution of alteration phases were redrawn for Ocean Drilling Program Sites 1188 and 1189.