Environmental and behavioral risk factors for moderate or severe rotavirus diarrhea in children less than 24 months

On a global basis rotaviruses are the most important agents involved in childhood diarrhea. In developing countries they account for 6% of all diarrheas and 20% of all diarrhea related deaths of children under 5 years of age, with over 1 billion episodes and over 4 million deaths annually. Given the disease burden, there is a need for better understanding the risk factors involved in rotavirus disease, to identify areas of intervention. In order to provide this information, two areas were developed: a review of the literature, examining the causal evidence for rotavirus diarrhea and a case comparison study. The case comparison study analyzed two areas: identifying climate factors and, identifying environmental and behavioral risk factors. The literature review showed that few analytical studies have identified specific risk factors such as home environment, and a winter seasonal trend for temperate areas, but in key areas evidence is contradictory. The case comparison study for climate factors demonstrated that seasonality occurs in a tropical country like Venezuela and that a complex interplay between weather conditions contribute to the seasonal pattern. A positive association between rain fall (OR 4.1); dew point (OR 2.3) and temperature differential during the day (OR 1.4) and, an inverse association with temperature (OR 0.5) and relative humidity (OR 0.8) was found. This information is useful in understanding the seasonal pattern of rotavirus and for planning health care needs. The second analysis demonstrated that environmental variables such as crowding (OR 14.3), contact with someone with an infectious disease (OR 4.9) and animal ownership (OR 2.3) were important. Restricting the analysis to animal owners demonstrated that living In a rural settling (OR 13.8), defecating in inappropriate places (OR 7.2), crowding(4.2) and indoor animals (4.0) are of importance. Behavioral variables identified were: lack of breast feeding (OR 4.0) and visiting when someone was sick (OR 3.4). Biological and demographic variables of importance were: age, with a dose response relationship; undernurishment (OR 11.3) and household per capita monthly income less than US $ 16.30 (OR 8.5). Using a diarrhea compeer group we found that, although some of the previous variables were of importance, no major differences were found. These findings are important in identifying paths for prevention and further research. ^

Progressive regression of left ventricular hypertrophy two years after bariatric surgery.

BACKGROUND: Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. We hypothesized that the decrease in fat mass and lean mass after weight loss surgery is associated with a decrease in left ventricular mass. METHODS: Fifteen severely obese women (mean body mass index [BMI]: 46.7+/-1.7 kg/m(2)) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic metabolism, together with body mass index (BMI), waist and hip circumferences, body composition (fat mass and lean mass), and resting energy expenditure were measured at 0, 3, 9, 12, and 24 months. RESULTS: Left ventricular mass continued to decrease linearly over the entire period of observation, while rates of weight loss, loss of lean mass, loss of fat mass, and resting energy expenditure all plateaued at 9 [corrected] months (P <.001 for all). Parameters of systemic metabolism normalized by 9 months, and showed no further change at 24 months after surgery. CONCLUSIONS: Even though parameters of obesity, including BMI and body composition, plateau, the benefits of bariatric surgery on systemic metabolism and left ventricular mass are sustained. We propose that the progressive decrease of left ventricular mass after weight loss surgery is regulated by neurohumoral factors, and may contribute to improved long-term survival.

Body weight, insulin resistance, and serum adipokine levels 2 years after 2 types of bariatric surgery.

OBJECTIVE: Bariatric surgery reverses obesity-related comorbidities, including type 2 diabetes mellitus. Several studies have already described differences in anthropometrics and body composition in patients undergoing Roux-en-Y gastric bypass compared with laparoscopic adjustable gastric banding, but the role of adipokines in the outcomes after the different types of surgery is not known. Differences in weight loss and reversal of insulin resistance exist between the 2 groups and correlate with changes in adipokines. METHODS: Fifteen severely obese women (mean body mass index [BMI]: 46.7 kg/m(2)) underwent 2 types of laparoscopic weight loss surgery (Roux-en-Y gastric bypass=10, adjustable gastric banding=5). Weight, waist and hip circumference, body composition, plasma metabolic markers, and lipids were measured at set intervals during a 24-month period after surgery. RESULTS: At 24 months, patients who underwent Roux-en-Y were overweight (BMI 29.7 kg/m(2)), whereas patients who underwent gastric banding remained obese (BMI 36.3 kg/m(2)). Patients who underwent Roux-en-Y lost significantly more fat mass than patients who underwent gastric banding (mean difference 16.8 kg, P<.05). Likewise, leptin levels were lower in the patients who underwent Roux-en-Y (P=.003), and levels correlated with weight loss, loss of fat mass, insulin levels, and Homeostasis Model of Assessment 2. Adiponectin correlated with insulin levels and Homeostasis Model of Assessment 2 (r=-0.653, P=.04 and r=-0.674, P=.032, respectively) in the patients who underwent Roux-en-Y at 24 months. CONCLUSION: After 2 years, weight loss and normalization of metabolic parameters were less pronounced in patients who underwent gastric banding compared with patients who underwent Roux-en-Y gastric bypass. Our findings require confirmation in a prospective randomized trial.

{\it In vivo\/} induction of DNA changes in cervicovaginal epithelium by perinatal estrogen exposure

Epidemiological studies have associated estrogens with human neoplasm such as the endometrium, cervix, vagina, breast, and liver. Perinatal exposure to natural (17$\beta$-estradiol (17$\beta$-E$\sb2)\rbrack$ and synthetic (diethylstilbestrol (DES)) estrogens induces neoplastic changes in humans and rodents. Previous studies demonstrated that neonatal 17$\beta$-E$\sb2$ treatment increased the nuclear DNA content of mouse cervicovaginal epithelium that preceded histologically evident neoplasia. In order to determine whether this effect was specific to 17$\beta$-E$\sb2,$ associated with chromosomal changes, and relevant to the human, female BALB/c mice were treated neonatally with either 17$\alpha$-estradiol (17$\alpha$-E$\sb2)$ and 5$\beta$-dihydrotestosterone ($5\beta$-DHT), both inactive steroids in adult reproductive tissue, or 17$\beta$-E$\sb2.$ Ten-day-old mice received pellet implants of 17$\beta$-E$\sb2,$ 17$\alpha$-E$\sb2,$ $5\beta$-DHT, or cholesterol. Seventy-day-old cervicovaginal tracts were examined histologically and flow cytometrically. 17$\beta$-E$\sb2$-treated animals were evaluated by fluorescent in situ hybridization (FISH) using a probe specific for chromosome 1. Trisomy of chromosomes 1, 7, 11, and 17 was evaluated by FISH in cervicovaginal material from 19 DES-exposed and 19 control patients.^ $17\beta$-E$\sb2, 17\alpha$-E$\sb2$, and $5\beta$-DHT-induced dramatic developmental and histological changes in the cervicovaginal tract, including hypospadia, hyperplasia, and persistent cornification. The changes induced by 17$\alpha$-E$\sb2$ were equivalent to 17$\beta$-E$\sb2.$ Neonatal 17$\alpha$-E$\sb2$-induced adenosquamous cervicovaginal tumors at 24 months. 17$\alpha$-E$\sb2$ and $5\beta$-DHT significantly increased the nuclear DNA content over control animals, but at significantly lower levels than 17$\beta$-E$\sb2.$ DNA ploidy changes were highest (80%) in animals treated neonatally and secondarily with 17$\beta$-E$\sb2.$ Secondary 17$\alpha$-E$\sb2$ and $5\beta$-DHT administration, unlike 17$\beta$-E$\sb2,$ didn't significantly increase DNA content. Chromosome 1 trisomy incidence was 66% in neonatal 17$\beta$-E$\sb2$-treated animals. Trisomy was evident in 4 DES-exposed patients: one patient with trisomy of chromosomes 1, 7, and 11; one patient with chromosome 7 trisomy; and two patients with chromosome 1 trisomy. These data demonstrated the biological effects of 17$\alpha$-E$\sb2$ and $5\beta$-DHT were age-dependent, 17$\alpha$-E$\sb2$ was equivalent to 17$\beta$-E$\sb2$ and tumorigenic when administered neonatally, and histological changes were not steroid specific. Chromosomal changes were associated with increased nuclear DNA content and chromosomal changes may be an early event in the development of tumors in human DES-exposed tissues. ^

Household risk factors and the health and nutritional status of children in rural Honduras

During this cross-sectional study, both quantitative and qualitative research methods were used to elucidate the role that household environment and sanitation play in the nutritional status of children in a rural Honduran community. Anthropometric measurements were taken as measures of nutritional status among children under five years of age, while interviews regarding the household environment were conducted with their primary caregivers. Community participatory activities were conducted with primary caregivers, and results from water quality testing were analyzed for E. coli contamination. Anthropometric results were compared using the 1977 NCHS Growth Charts and the 2006 WHO Child Growth Standard to examine the implications of using the new WHO standard. The references showed generally good or excellent agreement between z-score categories, except among height-for-age classifications for males 24-35.9 months and weight-for-age classifications for males older than 24 months. Comparing the proportion of stunted, underweight, and wasted children, using the WHO standard generally resulted in higher proportions of stunting, lower underweight proportions, and higher overweight proportions. Logistic regression was used to determine which household and sanitation factors most influenced the growth of children. Results suggest only having water from a spring, stream, or other type of surface water as the primary source of drinking water is a significant risk factor for stunting. A protective association was seen between the household wealth index and stunting. Through participatory activities, the community provided insight on health issues important for improving child health. These activities yielded findings to be harnessed as a powerful resource to unify efforts for change. The qualitative findings were triangulated with the quantitative interview and water testing results to provide intervention recommendations for the community and its primary health care clinic. Recommendations include educating the community on best water consumption practices and encouraging the completion of at least some primary education for primary caregivers to improve child health. It is recommended that a community health worker program be developed to support and implement community interventions to improve water use and household sanitation behaviors and to encourage the involvement of the community in targeting and guiding successful interventions. ^

Role of ovarian cancer antigen CA125/MUC16 in development and cancer

Cancer antigen 125 (CA125) is a tumor antigen that is routinely used to monitor the disease progress and the outcome of treatment in ovarian cancer patients. Elevated serum levels of CA125 are detected in over 80% of epithelial ovarian cancer patients. CA125 is a high molecular weight (>1M Dalton) mucin-type glycoprotein encoded by the MUC16 gene on human chromosome 19. Although MUC16 has served as the best serum marker for monitoring growth of ovarian cancer, roles for MUC16 in normal physiology and ovarian cancer are largely unknown. To understand the biological functions of MUC16, I characterized a mouse Muc16 homolog on chromosome 9 by means of expression pattern profiling, phenotype analysis of Muc16 knockout mice, and in vitro and in vivo studies of Muc16 null transformed ovarian surface epithelial (OSE) cells. ^ The mouse Muc16 homolog shares a conserved genomic structure with human MUC16. In addition to being expressed in mouse ovarian cancer, mouse Muc16 mRNA and protein were expressed in the mesothelia covering the heart, lung, ovary, oviduct, spleen, testis, and uterus. The conserved genomic structure and expression pattern of mouse Muc16 to human MUC16 suggests that mouse Muc16 is the ortholog of human MUC16. To understand the biological functions of Muc16, I generated Muc16 knockout mice. Muc16 knockout mice were viable, fertile and normal by one year of age. However, between 18 and 24 months of age, Muc16 knockout mice developed various tissue abnormalities such as ovarian cysts and tumors of the liver and other peritoneal organs. To determine the role of MUC16 in ovarian cancer progression, I established Muc16 null transformed ovarian surface epithelial (OSE) cell lines, following the same method to develop mouse model of epithelial ovarian cancer (Orsulic et al., 2002). Loss of Muc16 did not affect cell morphology, cell proliferation rate, or tumorigenic potential. However, Muc16-null OSE cells showed decreased attachment to extracellular matrix proteins as well as to primary mouse peritoneal mesothelial cells. Peritoneal mesothelia are the most frequent implantation sites of ovarian cancer. Furthermore, a pilot transplantation assay suggests that Muc16 null transformed OSE cells formed less disseminated tumors in the peritoneal cavity compared to wild-type OSE cells. ^ In conclusion, these results demonstrate that MUC16 is not required for normal mouse development or reproduction, but plays important roles in tissue homeostasis, ovarian cancer cell adhesion and dissemination. This study provides the first in vivo evidence of the roles of MUC16 in development, as well as ovarian cancer progression and dissemination. These studies offer valuable insights into possible mechanisms of ovarian cancer development and potential molecular targets for ovarian cancer treatment. ^

Secondary data analysis of lead screening compliance in high-risk children

Introduction. Despite the ban of lead-containing gasoline and paint, childhood lead poisoning remains a public health issue. Furthermore, a Medicaid-eligible child is 8 times more likely to have an elevated blood lead level (EBLL) than a non-Medicaid child, which is the primary reason for the early detection lead screening mandate for ages 12 and 24 months among the Medicaid population. Based on field observations, there was evidence that suggested a screening compliance issue. Objective. The purpose of this study was to analyze blood lead screening compliance in previously lead poisoned Medicaid children and test for an association between timely lead screening and timely childhood immunizations. The mean months between follow-up tests were also examined for a significant difference between the non-compliant and compliant lead screened children. Methods. Access to the surveillance data of all childhood lead poisoned cases in Bexar County was granted by the San Antonio Metropolitan Health District. A database was constructed and analyzed using descriptive statistics, logistic regression methods and non-parametric tests. Lead screening at 12 months of age was analyzed separately from lead screening at 24 months. The small portion of the population who were also related were included in one analysis and removed from a second analysis to check for significance. Gender, ethnicity, age of home, and having a sibling with an EBLL were ruled out as confounders for the association tests but ethnicity and age of home were adjusted in the nonparametric tests. Results. There was a strong significant association between lead screening compliance at 12 months and childhood immunization compliance, with or without including related children (p<0.00). However, there was no significant association between the two variables at the age of 24 months. Furthermore, there was no significant difference between the median of the mean months of follow-up blood tests among the non-compliant and compliant lead screened population for at the 12 month screening group but there was a significant difference at the 24 month screening group (p<0.01). Discussion. Descriptive statistics showed that 61% and 56% of the previously lead poisoned Medicaid population did not receive their 12 and 24 month mandated lead screening on time, respectively. This suggests that their elevated blood lead level may have been diagnosed earlier in their childhood. Furthermore, a child who is compliant with their lead screening at 12 months of age is 2.36 times more likely to also receive their childhood immunizations on time compared to a child who was not compliant with their 12 month screening. Even though there was no statistical significant association found for the 24 month group, the public health significance of a screening compliance issue is no less important. The Texas Medicaid program needs to enforce lead screening compliance because it is evident that there has been no monitoring system in place. Further recommendations include a need for an increased focus on parental education and the importance of taking their children for wellness exams on time.^

The Impact of Title IV-E Training on Case Outcomes for Children Serviced by CPS

This study was designed to determine if the professional social work education provided by Title IV-E stipends leads to better case outcomes for children serviced by a southern state in the U.S. Desired case outcomes included lower levels of recurrence of child maltreatment, lower levels of foster care re-entries, greater stability of foster care placements, more reunifications with families within 12 months of placement in foster care, and more adoptions within 24 months of being placed in foster care. Data were obtained from the state’s case outcome records. The findings from the study indicate that Title IV-E stipend workers had significantly better outcomes than Non-Title IV-E workers in two areas: reunifications within twelve months and finalized adoptions within twenty-four months. In addition, non-Title IV-E workers with social work degrees were significantly more likely to achieve positive outcomes regarding recurrence of maltreatment, stability of foster care placement, and length of time to achieve adoption. The study recommends that state child protective service (CPS) agencies continue to offer Title IV-E child welfare training programs and hire degreed social workers. CPS should also continue to support the Title IV-E program and encourage employees to participate in the program. In addition, it is recommended that jobs be restructured to maximize activities that positively impact case outcomes and that the salaries of CPSworkers be increased. Additional research should also be conducted to contribute to a better understanding of other factors that positively impact case outcomes.

In-utero exposure to chemotherapy: What are the long term effects?

There is not a large body of evidence on in-utero exposure to chemotherapy for pregnancy-associated cancers to help determine the long term effects on offspring. This study is a systematic review of long term follow-up to find evidence for adverse outcomes in exposed offspring. In order for studies to be eligible for this systematic review, they had to have a median follow up of at least 24 months with the resulting child. PubMed, Medline, and Scopus were the databases used, and we included all eligible articles, regardless of the date of publication. The search resulted in six articles meeting the eligibility requirements. The review of findings of these studies suggested that there is not enough evidence to make a determination of the risk of chemotherapy for the offspring. Exposed children in the sample of reviewed papers did have some medical conditions, but the rate and type did not differ from the non-exposed population. However, a limitation of this literature review is the very small sample size of publications on this important topic. This finding of few studies on this topic is an important result of this systematic review. More research and long term follow-up studies must be conducted to address this issue.^