Acute and Chronic Altitude-Induced Cognitive Dysfunction in Children and Adolescents.

OBJECTIVE To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. STUDY DESIGN We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. RESULTS Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. CONCLUSIONS Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities.

Predicting 5- and 10-year survival in older women with early-stage breast cancer: self-rated health and walking ability.

OBJECTIVES To determine life expectancy for older women with breast cancer. DESIGN Prospective longitudinal study with 10 years of follow-up data. SETTING Hospitals or collaborating tumor registries in four geographic regions (Los Angeles, California; Minnesota; North Carolina; Rhode Island). PARTICIPANTS Women aged 65 and older at time of breast cancer diagnosis with Stage I to IIIA disease with measures of self-rated health (SRH) and walking ability at baseline (N = 615; 17% aged ≥80, 52% Stage I, 58% with ≥2 comorbidities). MEASUREMENTS Baseline SRH, baseline self-reported walking ability, all-cause and breast cancer-specific estimated probability of 5- and 10-year survival. RESULTS At the time of breast cancer diagnosis, 39% of women reported poor SRH, and 28% reported limited ability to walk several blocks. The all-cause survival curves appear to separate after approximately 3 years, and the difference in survival probability between those with low SRH and limited walking ability and those with high SRH and no walking ability limitation was significant (0.708 vs 0.855 at 5 years, P ≤ .001; 0.300 vs 0.648 at 10 years, P < .001). There were no differences between the groups in breast cancer-specific survival at 5 and 10 years (P = .66 at 5 years, P = .16 at 10 years). CONCLUSION The combination of low SRH and limited ability to walk several blocks at diagnosis is an important predictor of worse all-cause survival at 5 and 10 years. These self-report measures easily assessed in clinical practice may be an effective strategy to improve treatment decision-making in older adults with cancer.

T- and B-cell responses and previous exposure to hepatitis B virus in 'anti-HBc alone' patients.

A serologic response to hepatitis B virus (HBV) defined as 'anti-HBc alone' is commonly observed, but its significance remains unclear. This study aimed to define the relationship between 'anti-HBc alone' serostatus and HBV infection, including HBV-specific T- and B-cell memory responses. We enrolled 31 'anti-HBc alone' patients. Total HBV DNA and cccDNA were tested by nested polymerase chain reaction (PCR) analysis in liver samples from 22 'anti-HBc alone' patients vs controls (chronic or resolved HBV infection), followed by HBsAg/HBcAg immunohistochemical (IHC) staining. IFN-γ secretion by HBV-specific T cells was compared in individuals who were 'anti-HBc alone' (n = 27), resolved HBV (n = 21), chronic HBV (n = 24) and 12 healthy controls using enzyme-linked immunospot (ELISpot) assays. An HBsAg-IgG B-cell ELISpot assay was performed in 'anti-HBc alone' patients before and after one dose of recombinant HBsAg vaccine. The majority (23/31, 74.2%) of the 'anti-HBc alone' individuals were co-infected with HCV. Infrequent intrahepatic total HBV DNA (2/22, 9.1%) and cccDNA (1/22, 4.5%) were detected in biopsies; HBsAg and HBcAg IHC staining was negative. HBV-specific T-cell responses were similar between 'anti-HBc alone' individuals and HBV resolvers. Circulating HBV-memory B-cell responses were detected in all 'anti-HBc alone' individuals, consistent with an HBsAg-specific memory pool. After one HBV vaccine dose, increased anti-HBs antibody levels were observed, accompanied by an expansion of HBsAg-specific memory B cells (P = 0.0226). 'Anti-HBc alone' individuals showed HBV-specific T-cell and memory B-cell responses typical of previous viral exposure and protective memory, suggesting a resolved infection.

Dish Detection and Segmentation for Dietary Assessment on Smartphones

Diet-related chronic diseases severely affect personal and global health. However, managing or treating these diseases currently requires long training and high personal involvement to succeed. Computer vision systems could assist with the assessment of diet by detecting and recognizing different foods and their portions in images. We propose novel methods for detecting a dish in an image and segmenting its contents with and without user interaction. All methods were evaluated on a database of over 1600 manually annotated images. The dish detection scored an average of 99% accuracy with a .2s/image run time, while the automatic and semi-automatic dish segmentation methods reached average accuracies of 88% and 91% respectively, with an average run time of .5s/image, outperforming competing solutions.

The RNA binding proteins RBM38 and DND1 are repressed in AML and have a novel function in APL differentiation

The RNA binding proteins RBM binding motif protein 38 (RBM38) and DEAD END 1 (DND1) selectively stabilize mRNAs by attenuating RNAse activity or protecting them from micro(mi)RNA-mediated cleavage. Furthermore, both proteins can efficiently stabilize the mRNA of the cell cycle inhibitor p21(CIP1). Since acute myeloid leukemia (AML) differentiation requires cell cycle arrest and RBM38 as well as DND1 have antiproliferative functions, we hypothesized that decreased RBM38 and DND1 expression may contribute to the differentiation block seen in this disease. We first quantified RBM38 and DND1 mRNA expression in clinical AML patient samples and CD34(+) progenitor cells and mature granulocytes from healthy donors. We found significantly lower RBM38 and DND1 mRNA levels in AML blasts and CD34(+) progenitor cells as compared to mature neutrophils from healthy donors. Furthermore, the lowest expression of both RBM38 and DND1 mRNA correlated with t(8;21). In addition, neutrophil differentiation of CD34(+) cells in vitro with G-CSF (granulocyte colony stimulating factor) resulted in a significant increase of RBM38 and DND1 mRNA levels. Similarly, neutrophil differentiation of NB4 acute promyelocytic leukemia (APL) cells was associated with a significant induction of RBM38 and DND1 expression. To address the function of RBM38 and DND1 in neutrophil differentiation, we generated two independent NB4RBM38 as well as DND1 knockdown cell lines. Inhibition of both RBM38 and DND1 mRNA significantly attenuated NB4 differentiation and resulted in decreased p21(CIP1) mRNA expression. Our results clearly indicate that expression of the RNA binding proteins RBM38 and DND1 is repressed in primary AML patients, that neutrophil differentiation is dependent on increased expression of both proteins, and that these proteins have a critical role in regulating p21(CIP1) expression during APL differentiation.

Hepatitis B Infection, Viral Load and Resistance in HIV-Infected Patients in Mozambique and Zambia.

BACKGROUND Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. METHODS We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. RESULTS Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192-8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22-5.53) and CD4 cell count below 200/μl (2.58, 1.20-5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. CONCLUSION One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults.

A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection.

Sentinel lymph node (SLN) detection techniques have the potential to change the standard of surgical care for patients with prostate cancer. We performed a lymphatic mapping study and determined the value of fluorescence SLN detection with indocyanine green (ICG) for the detection of lymph node metastases in intermediate- and high-risk patients undergoing radical prostatectomy and extended pelvic lymph node dissection. A total of 42 patients received systematic or specific ICG injections into the prostate base, the midportion, the apex, the left lobe, or the right lobe. We found (1) that external and internal iliac regions encompass the majority of SLNs, (2) that common iliac regions contain up to 22% of all SLNs, (3) that a prostatic lobe can drain into the contralateral group of pelvic lymph nodes, and (4) that the fossa of Marcille also receives significant drainage. Among the 12 patients who received systematic ICG injections, 5 (42%) had a total of 29 lymph node metastases. Of these, 16 nodes were ICG positive, yielding 55% sensitivity. The complex drainage pattern of the prostate and the low sensitivity of ICG for the detection of lymph node metastases reported in our study highlight the difficulties related to the implementation of SNL techniques in prostate cancer. PATIENT SUMMARY There is controversy about how extensive lymph node dissection (LND) should be during prostatectomy. We investigated the lymphatic drainage of the prostate and whether sentinel node fluorescence techniques would be useful to detect node metastases. We found that the drainage pattern is complex and that the sentinel node technique is not able to replace extended pelvic LND.

Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation

Aldosterone is an important factor supporting placental growth and fetal development. Recently, expression of placental growth factor (PlGF) has been observed in response to aldosterone exposure in different models of atherosclerosis. Thus, we hypothesized that aldosterone up-regulates growth-adaptive angiogenesis in pregnancy, via increased placental PlGF expression. We followed normotensive pregnant women (n = 24) throughout pregnancy and confirmed these results in a second independent first trimester cohort (n = 36). Urinary tetrahydroaldosterone was measured by gas chromatography-mass spectrometry and corrected for creatinine. Circulating PlGF concentrations were determined by ELISA. Additionally, cultured cell lines, adrenocortical H295R and choriocarcinoma BeWo cells, as well as primary human third trimester trophoblasts were tested in vitro. PlGF serum concentrations positively correlated with urinary tetrahydroaldosterone corrected for creatinine in these two independent cohorts. This observation was not due to PlGF, which did not induce aldosterone production in cultured H295R cells. On the other hand, PlGF expression was specifically enhanced by aldosterone in the presence of forskolin (p < 0.01) in trophoblasts. A pronounced stimulation of PlGF expression was observed with reduced glucose concentrations simulating starvation (p < 0.001). In conclusion, aldosterone stimulates placental PlGF production, enhancing its availability during human pregnancy, a response amplified by reduced glucose supply. Given the crucial role of PlGF in maintaining a healthy pregnancy, these data support a key role of aldosterone for a healthy pregnancy outcome.

A randomized trial of the effects of the noble gases helium and argon on neuroprotection in a rodent cardiac arrest model.

BACKGROUND The noble gas xenon is considered as a neuroprotective agent, but availability of the gas is limited. Studies on neuroprotection with the abundant noble gases helium and argon demonstrated mixed results, and data regarding neuroprotection after cardiac arrest are scant. We tested the hypothesis that administration of 50% helium or 50% argon for 24 h after resuscitation from cardiac arrest improves clinical and histological outcome in our 8 min rat cardiac arrest model. METHODS Forty animals had cardiac arrest induced with intravenous potassium/esmolol and were randomized to post-resuscitation ventilation with either helium/oxygen, argon/oxygen or air/oxygen for 24 h. Eight additional animals without cardiac arrest served as reference, these animals were not randomized and not included into the statistical analysis. Primary outcome was assessment of neuronal damage in histology of the region I of hippocampus proper (CA1) from those animals surviving until day 5. Secondary outcome was evaluation of neurobehavior by daily testing of a Neurodeficit Score (NDS), the Tape Removal Test (TRT), a simple vertical pole test (VPT) and the Open Field Test (OFT). Because of the non-parametric distribution of the data, the histological assessments were compared with the Kruskal-Wallis test. Treatment effect in repeated measured assessments was estimated with a linear regression with clustered robust standard errors (SE), where normality is less important. RESULTS Twenty-nine out of 40 rats survived until day 5 with significant initial deficits in neurobehavioral, but rapid improvement within all groups randomized to cardiac arrest. There were no statistical significant differences between groups neither in the histological nor in neurobehavioral assessment. CONCLUSIONS The replacement of air with either helium or argon in a 50:50 air/oxygen mixture for 24 h did not improve histological or clinical outcome in rats subjected to 8 min of cardiac arrest.

A program manual to assist with implementation of a volunteer health and wellness program

Based on the success of a community health and wellness program, Wellness in the City, delivered in Dallas County by trained volunteers, Texas Cooperative Extension (TCE) decided to pilot the program in 16 counties in North and East Texas. Before implementing the program, TCE wanted the Dallas County program to be reviewed and revised as needed to meet the diverse community needs in the pilot counties. TCE also asked for an implementation manual to be developed for the county agents to utilize. ^ To achieve these objectives, I first reviewed literature on other volunteer-implemented health interventions in the U.S. to see how they were planned, disseminated, implemented, and evaluated. Next, I reviewed the Wellness in the City program and materials. I applied all the information I gathered up to that point to the program development committee meetings (committee included seven TCE county agents, a TCE regional program director, and me). The program structure and training materials were revised based on our research and program implementation experience. These changes were made to ensure adequate training for the volunteers and to create a program that is applicable in the communities it will be piloted in. ^ With the program structure and training presentations developed, next I focused on compiling the implementation manual, which includes program details and volunteer recruitment, training, and management materials. The goal was to create a manual with everything the county agents will need to implement the program, so they can focus their efforts on putting the manual to use and recruiting and managing the volunteers. The final step was developing a program evaluation form for the agents to complete. It includes questions to assess the agents' thoughts about the training content, the feasibility of implementing the program using the manual, and the challenges of the program. ^

Evaluation of racial and ethnic disparities of glycemic control in the Health and Retirement Study. 2003 Diabetes Survey

Objective. To examine and evaluate racial and ethnic disparities in glycemic control among HRS respondents with diabetes aged 55-94 years. ^ Methods. The HRS Diabetes 2003 database provides data on blood-drawn glycemic control and self-reported demographics, socioeconomic status, clinical, health access and self-care characteristics. 1,141 non-Hispanic White, non-Hispanic Black, and Hispanic respondents were included in multiple logistic regression of glycemic control. ^ Results. The rate of poor control was significantly higher among Blacks (61.5%, 105/171) and Hispanics (65.3% 72/110) than among Whites (45.0% 387/860) (p < 0.01). After controlling for influential covariates and interactions, Blacks and Hispanics had a three-fold increased risk for poor control compared to Whites when duration was five years or less. ^ Conclusions. Clinical and self-perception variables, like duration, medication, and self-rated poor diabetes control affected glycemic control independent of race and ethnicity, but there remains unexplained racial and ethnic disparities for newly-diagnosed individuals. This is the first study to find an interaction between duration and race and ethnicity on glycemic control. Future research should incorporate cultural beliefs and attitudes about diabetes control that may explain the racial and ethnic disparity. ^

A formative evaluation of the American Diabetes Association's Choosing Health and Sensible Exercise childhood obesity intervention

Background. The increasing prevalence of overweight among youth in the United States, and the parallel rise in related medical comorbidities has led to a growing need for efficient weight-management interventions. Purpose. The aim of this study was to evaluate the effects of the Choosing Health and Sensible Exercise (C.H.A.S.E.) childhood obesity prevention program on Body Mass Index (BMI), physical activity and dietary behaviors. Methods. This study utilized de-identified data collected during the fall 2006 session of the C.H.A.S.E. program. A total of 65 students at Woodview Elementary School and Deepwater Elementary School participated in this intervention. The C.H.A.S.E. program is a 10-week obesity prevention program that focuses on nutrition and physical activity education. Collection of height and weight data, and a health behavior survey was conducted during the first and last week of the intervention. Paired t-tests were used to determine statistically significant differences between pre- and post-intervention measurements. One-way analysis of variance was used to adjust for potential confounders, such as gender, age, BMI category ("normal weight", "at risk overweight", or "overweight"), and self-reported weight loss goals. Data were analyzed using STATA, v. 9.2. Results. A significant decrease in mean BMI (p< 0.05) was found after the 10-week intervention. While the results were statistically significant for the group as a whole, changes in BMI were not significant when stratified by age, sex, or ethnicity. The mean overall scores for the behavior survey did not change significantly pre- and post-intervention; however, significant differences were found in the dietary intention scale, indicating that students were more likely to intend to make healthier food choices (p<0.05). No statistically significant decreases in BMI were found when stratified for baseline BMI-for-age percentiles or baseline weight loss efforts (p>0.05). Conclusion. The results of this evaluation provide information that will be useful in planning and implementing an effective childhood obesity intervention in the future. Changes in the self-reported dietary intentions and BMI show that the C.H.A.S.E. program is capable of modifying food choice selection and decreasing BMI. Results from the behavior questionnaire indicate that students in the intervention program were making changes in a positive direction. Future implementation of the C.H.A.S.E. program, as well as other childhood obesity interventions, may want to consider incorporating additional strategies to increase knowledge and other behavioral constructs associated with decreased BMI. In addition, obesity prevention programs may want to increase parental involvement and increase the dose or intensity of the intervention. ^

Improving the health and well-being of women at risk for neural tube defect recurrence

There is growing interest in providing women with internatal care, a package of healthcare and ancillary services that can improve their health during the period after the termination of one pregnancy but before the conception of the next pregnancy. Women who have had a pregnancy affected by a neural tube defect can especially benefit from internatal care because they are at increased risk for recurrence and improvements to their health during the inter-pregnancy period can prevent future negative birth outcomes. The dissertation provides three papers that inform the content of internatal care for women at risk for recurrence by examining descriptive epidemiology to develop an accurate risk profile of the population, assessing whether women at risk for recurrence would benefit from a psychosocial intervention, and determining how to improve health promotion efforts targeting folic acid use.^ Paper one identifies information relevant for developing risk profiles and conducting risk assessments. A number of investigations have found that the risk for neural tube defects differs between non-Hispanic Whites and Hispanics. To understand the risk difference, the descriptive epidemiology of spina bifida and anencephaly was examined for Hispanics and non-Hispanic Whites based on data from the Texas Birth Defects Registry for the years 1999 through 2004. Crude and adjusted birth prevalence ratios and corresponding 95% confidence intervals were calculated between descriptive epidemiologic characteristics and anencephaly and spina bifida for non-Hispanic Whites and for Hispanics. In both race/ethnic groups, anencephaly expressed an inverse relationship with maternal age and a positive linear relationship with parity. Both relationships were stronger in non-Hispanic Whites. Female infants had a higher risk for anencephaly in non-Hispanic Whites. Lower maternal education was associated with increased risk for spina bifida in Hispanics.^ Paper two assesses the need for a psychosocial intervention. For mothers who have children with spina bifida, the transition to motherhood can be stressful. This qualitative study explored the process of becoming a mother to a child with spina bifida focusing particularly on stress and coping in the immediate postnatal environment. Semi-structured interviews were conducted with six mothers who have children with spina bifida. Mothers were asked about their initial emotional and problem-based coping efforts, the quality and kind of support provided by health providers, and the characteristics of their meaning-based coping efforts; questions matched Transactional Model of Stress and Coping (TMSC) constructs. Analysis of the responses revealed a number of modifiable stress and coping transactions, the most salient being: health providers are in a position to address beliefs about self-causality and prevent mothers from experiencing the repercussions that stem from maintaining these beliefs. ^ Paper three identifies considerations when creating health promotion materials targeting folic acid use. A brochure was designed using concepts from the Precaution Adoption Process Model (PAPM). Three focus groups comprising 26 mothers of children with spina bifida evaluated the brochure. One focus group was conducted in Spanish-only, the other two focus groups were conducted in English and Spanish combined. Qualitative analysis of coded transcripts revealed that a brochure is a helpful adjunct. Questions about folic acid support the inclusion of an insert with basic information. There may be a need to develop different educational material for Hispanics so the importance of folic acid is provided in a situational context. Some participants blamed themselves for their pregnancy outcome which may affect their receptivity to messages in the brochure. The women's desire for photographs that affect their perception of threat and their identification with the second role model indicate they belong to PAPM Stage 2 and 3. Participants preferred colorful envelopes, high quality paper, intimidating photographs, simple words, conversational style sentences, and positive messages.^ These papers develop the content of risk assessment, psychosocial intervention, and health promotion components of internatal care as they apply to women at risk for recurrence. The findings provided evidence for considering parity and maternal age when assessing nutritional risk. The two dissimilarities between the two race/ethnic groups, infant sex and maternal education lent support to creating separate risk profiles. Interviews with mothers of children with spina bifida revealed the existence of unmet needs-suggesting that a psychosocial intervention provided as part of internatal care can strengthen and support women's well-being. Segmenting the audience according to race/ethnicity and PAPM stage can improve the relevance of print materials promoting folic acid use.^

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. ^

Demographic and social factors which influence periodontal disease using the National Health and Nutritional Examination Survey (NHANES)

Periodontal diseases include the various forms of gingivitis and periodontitis. Scientific literature submits 80% of the population suffers from some form of periodontal disease. The comparison of studies measuring periodontal disease is difficult because researchers use various parameters and indexes to define disease severity. The purposes of this paper were to examine the associations of gingival bleeding and 3 or more millimeters periodontal attachment loss, and age, sex, income, race/ethnicity, current tobacco use, dental visits, health insurance, stroke, heart attack, and diabetes using the periodontal examination population from the National Health and Nutritional Examination Survey (NHANES) 1999-2004. ^ When all risk factors were analyzed in the model as a whole sex, race/ethnicity, poverty, and education were statistically significant for bleeding on probing. When all risk factors were analyzed in the model as a whole sex, age, and education were statistically significant for loss of attachment. ^