Serologic and molecular evidence for Testudinid herpesvirus 2 infection in wild Agassiz's desert tortoises, Gopherus agassizii

Following field observations of wild Agassiz's desert tortoises (Gopherus agassizii) with oral lesions similar to those seen in captive tortoises with herpesvirus infection, we measured the prevalence of antibodies to Testudinid herpesvirus (TeHV) 3 in wild populations of desert tortoises in California. The survey revealed 30.9% antibody prevalence. In 2009 and 2010, two wild adult male desert tortoises, with gross lesions consistent with trauma and puncture wounds, respectively, were necropsied. Tortoise 1 was from the central Mojave Desert and tortoise 2 was from the northeastern Mojave Desert. We extracted DNA from the tongue of tortoise 1 and from the tongue and nasal mucosa of tortoise 2. Sequencing of polymerase chain reaction products of the herpesviral DNA-dependent DNA polymerase gene and the UL39 gene respectively showed 100% nucleotide identity with TeHV2, which was previously detected in an ill captive desert tortoise in California. Although several cases of herpesvirus infection have been described in captive desert tortoises, our findings represent the first conclusive molecular evidence of TeHV2 infection in wild desert tortoises. The serologic findings support cross-reactivity between TeHV2 and TeHV3. Further studies to determine the ecology, prevalence, and clinical significance of this virus in tortoise populations are needed.

Combining follow-up and change data is valid in meta-analyses of continuous outcomes: a meta-epidemiological study

OBJECTIVE To investigate whether it is valid to combine follow-up and change data when conducting meta-analyses of continuous outcomes. STUDY DESIGN AND SETTING Meta-epidemiological study of randomized controlled trials in patients with osteoarthritis of the knee/hip, which assessed patient-reported pain. We calculated standardized mean differences (SMDs) based on follow-up and change data, and pooled within-trial differences in SMDs. We also derived pooled SMDs indicating the largest treatment effect within a trial (optimistic selection of SMDs) and derived pooled SMDs from the estimate indicating the smallest treatment effect within a trial (pessimistic selection of SMDs). RESULTS A total of 21 meta-analyses with 189 trials with 292 randomized comparisons in 41,256 patients were included. On average, SMDs were 0.04 standard deviation units more beneficial when follow-up values were used (difference in SMDs: -0.04; 95% confidence interval: -0.13, 0.06; P=0.44). In 13 meta-analyses (62%), there was a relevant difference in clinical and/or significance level between optimistic and pessimistic pooled SMDs. CONCLUSION On average, there is no relevant difference between follow-up and change data SMDs, and combining these estimates in meta-analysis is generally valid. Decision on which type of data to use when both follow-up and change data are available should be prespecified in the meta-analysis protocol.

Obesity and overweight as a risk factor for pneumonia in polytrauma patients: a retrospective cohort study

BACKGROUND Obesity is a growing problem in western societies. The aim of this retrospective cohort study was to determine the association between the overweight and obese polytrauma patients and pneumonia after injury. METHODS A total of 628 patients with an Injury Severity Score (ISS) of 16 or greater and 16 years or older were included in this retrospective study. The sample was subdivided into three groups as follows: body mass index (BMI) of less than 25 kg/m2; BMI of 25 kg/m2 to 30 kg/m2; and BMI more than 30 kg/m2. The Murray score was assessed at admission and at its maximum during hospitalization to determine pulmonary problems. Pneumonia was defined as bacteriologically positive sputum with appropriate radiologic and laboratory changes (C-reactive protein and interleukin 6). Data are given as mean ± SEM. One-way analysis of variance and the Kruskal-Wallis test were used for the analyses, and the significance level was set at p < 0.05; Bonferroni-Dunn test was performed as post hoc analysis. RESULTS The Abbreviated Injury Scale (AIS) score for the thorax was 3.2 ± 0.1 in the group with a BMI of less than 25 kg/m2, 3.3 ± 0.1 in the group with a BMI of 25 kg/m2 to 30 kg/m2, and 2.8 ± 0.2 in the group with BMI of more than 30 kg/m2 (p = 0.044). The Murray score at admission was elevated with increasing BMI (0.8 ± 0.8 for BMI < 25 kg/m2, 0.9 ± 0.9 for BMI 25–30 kg/m2, and 1.0 ± 0.8 for BMI > 30 kg/m2; p = 0.137); the maximum Murray score during hospitalization revealed significant differences (1.2 ± 0.9 for BMI < 25 kg/m2, 1.6 ± 1.0 for BMI 25–30 kg/m2, and 1.5 ± 0.9 for BMI > 30 kg/m2; p < 0.001). The incidence of pneumonia also increased with increasing BMI (1.6% for BMI < 25 kg/m2, 2.0% for BMI 25–30 kg/m2, and 3.1% for BMI > 30 kg/m2; p = 0.044). CONCLUSION Obesity leads to an increased incidence of pneumonia in a polytrauma situation. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level IV.

Characterization and Clinical Relevance of ALDHbright Populations in Prostate Cancer

PURPOSE High aldehyde dehydrogenase (ALDH) has been suggested to selectively mark cells with high tumorigenic potential in established prostate cancer cell lines. However, the existence of cells with high ALDH activity (ALDH(bright)) in primary prostate cancer specimens has not been shown so far. We investigated the presence, phenotype, and clinical significance of ALDH(bright) populations in clinical prostate cancer specimens. EXPERIMENTAL DESIGN We used ALDEFLUOR technology and fluorescence-activated cell-sorting (FACS) staining to identify and characterize ALDH(bright) populations in cells freshly isolated from clinical prostate cancer specimens. Expression of genes encoding ALDH-specific isoforms was evaluated by quantitative real-time PCR in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer tissues. ALDH1A1-specific expression and prognostic significance were assessed by staining two tissue microarrays that included more than 500 samples of BPH, prostatic intraepithelial neoplasia (PIN), and multistage prostate cancer. RESULTS ALDH(bright) cells were detectable in freshly excised prostate cancer specimens (n = 39) and were mainly included within the EpCAM((+)) and Trop2((+)) cell populations. Although several ALDH isoforms were expressed to high extents in prostate cancer, only ALDH1A1 gene expression significantly correlated with ALDH activity (P < 0.01) and was increased in cancers with high Gleason scores (P = 0.03). Most importantly, ALDH1A1 protein was expressed significantly more frequently and at higher levels in advanced-stage than in low-stage prostate cancer and BPH. Notably, ALDH1A1 positivity was associated with poor survival (P = 0.02) in hormone-naïve patients. CONCLUSIONS Our data indicate that ALDH contributes to the identification of subsets of prostate cancer cells of potentially high clinical relevance.

Dusty punch cards and an eternal enigma: high-density lipoproteins and atherosclerosis

Epidemiological, clinical, and experimental evidence has accumulated during the last decades suggesting that high-density lipoproteins (HDLs) may protect from atherosclerosis and its clinical consequences. However, more than 55 years after the first description of the link between HDL and heart attacks, many facets of the biochemistry, function, and clinical significance of HDL remain enigmatic. This applies particularly to the completely unexpected results that became available from some recent clinical trials of nicotinic acid and of inhibitors of cholesteryl ester transfer protein (CETP). The concept that raising HDL cholesterol by pharmacological means would decrease the risk of vascular disease has therefore been challenged.

Self-reported attenuated psychotic-like experiences in help-seeking adolescents and their association with age, functioning and psychopathology

OBJECTIVE Self-rated attenuated psychotic-like experiences (APLEs) are increasingly used to screen for ultra-high-risk (UHR) across all ages. However, self-rated psychotic-like experiences (PLEs), in particular perception-related ones, were more frequent in children and adolescents, in which they possessed less clinical significance. We therefore explored the prevalence of different factors of APLEs in help-seeking adolescents, and their relationship with age, functioning and psychopathology METHOD As a part of the "Liberiamo il Futuro" project, help-seeking adolescents (N=171; 11-18years, 53% male) were screened with the 92-item Prodromal Questionnaire (PQ-92). A factor analysis was performed on the PQ-92 positive items (i.e., APLEs) to identify different APLE-factors. These were assessed for their association with age, functioning and psychopathology using regression analyses. RESULTS APLEs were very common in help-seeking adolescents, and formed four factors: "Conceptual Disorganization and Suspiciousness", "Perceptual Abnormalities", "Bizarre Experiences", and "Magical Ideation". Associations with age and functioning but not psychopathology were found for "Perceptual Abnormalities" that was significantly more severe in 11-12-year-olds, while "Conceptual Disorganization and Suspiciousness" was significantly related to psychopathology. CONCLUSION In line with findings on PLEs, prevalence and clinical significance of APLEs, especially perception-related ones, might depend on age and thus neurodevelopmental stage, and may fall within the normal spectrum of experience during childhood. This should be considered when screening for UHR status in younger age groups

The impact of body mass index and gender on the development of infectious complications in polytrauma patients

Purpose The aim was to test the impact of body mass index (BMI) and gender on infectious complications after polytrauma. Methods A total of 651 patients were included in this retrospective study, with an Injury Severity Score (ISS) C16 and age C16 years. The sample was subdivided into three groups: BMI\25 kg/m2, BMI 25–30 kg/m2, and BMI[30 kg/m2, and a female and a male group. Infectious complications were observed for 31 days after admission. Data are given as mean ± standard errors of the means. Analysis of variance, Kruskal–Wallis test, v2 tests, and Pearson’s correlation were used for the analyses and the significance level was set at P\0.05. Results The overall infection rates were 31.0 % in the BMI\25 kg/m2 group, 29.0 % in the BMI 25–30 kg/m2 group, and 24.5 % in the BMI[30 kg/m2 group (P = 0.519). The female patients developed significantly fewer infectious complications than the male patients (26.8 vs. 73.2 %; P\0.001). The incidence of death was significantly decreased according to the BMI group (8.8 vs. 7.2 vs. 1.5 %; P\0.0001) and the female population had a significantly lower mortality rate (4.1 vs. 13.4 %; P\0.0001). Pearson’s correlations between the Abbreviated Injury Scale (AIS) score and the corresponding infectious foci were not significant. Conclusion Higher BMI seems to be protective against polytrauma-associated death but not polytrauma-associated infections, and female gender protects against both polytrauma- associated infections and death. Understanding gender-specific immunomodulation could improve the outcome of polytrauma patients.

The roles of religiosity and affluence for adolescents' family orientation: Multilevel analyses of 18 cultures

Recent sociological and psychological debates concern the nature of the relation between changing religious beliefs and changing significance of the family. The current study analyzes multilevel relations between religiosity (personal and culture-level) and several aspects of family orientation for n = 4902 adolescents from 18 nations/areas from diverse cultural contexts covering a number of religious denominations with data from the Value-of-Children-Study (Trommsdorff & Nauck, 2005). In addition, cultural values from the World Values Survey representing religious versus secular values as well as survival versus self- expression values are examined at the cultural level of analysis as a joint effect with nation-level economic development. Results showed that religiosity/religious values were positively related to all aspects of adolescents’ family orientation at the individual as well as the cultural level, while societal affluence was only related to a loss of importance of the traditional and hierarchical aspects of family orientation. Postmaterialist self-expression values were unrelated to adolescents’ family orientation.

Epitheliocystis and the importance of Chlamydia-related bacteria on fish health

This book offers unique coverage of all presently known amoeba-resistant microorganisms and their significance in the study of infectious diseases. It highlights the role of free-living amoebae as a widespread evolutionary crib for the development of virulence traits in resistant microbes, including the ability of intracellular bacteria to survive to other phagocytic cells such as human macrophages. The emphasis is on public health risks associated with the presence in drinking water of intra-amoebal bacteria as well as the ecology and pathogenic role of amoebae-resisting bacteria as new emerging human pathogens

Insulin, CCAAT/enhancer-binding proteins and lactate regulate the human 11β-hydroxysteroid dehydrogenase type 2 gene expression in colon cancer cell lines.

11β-Hydroxysteroid dehydrogenases (11beta-HSD) modulate mineralocorticoid receptor transactivation by glucocorticoids and regulate access to the glucocorticoid receptor. The isozyme 11beta-HSD2 is selectively expressed in mineralocorticoid target tissues and its activity is reduced in various disease states with abnormal sodium retention and hypertension, including the apparent mineralocorticoid excess. As 50% of patients with essential hypertension are insulin resistant and hyperinsulinemic, we hypothesized that insulin downregulates the 11beta-HSD2 activity. In the present study we show that insulin reduced the 11beta-HSD2 activity in cancer colon cell lines (HCT116, SW620 and HT-29) at the transcriptional level, in a time and dose dependent manner. The downregulation was reversible and required new protein synthesis. Pathway analysis using mRNA profiling revealed that insulin treatment modified the expression of the transcription factor family C/EBPs (CCAAT/enhancer-binding proteins) but also of glycolysis related enzymes. Western blot and real time PCR confirmed an upregulation of C/EBP beta isoforms (LAP and LIP) with a more pronounced increase in the inhibitory isoform LIP. EMSA and reporter gene assays demonstrated the role of C/EBP beta isoforms in HSD11B2 gene expression regulation. In addition, secretion of lactate, a byproduct of glycolysis, was shown to mediate insulin-dependent HSD11B2 downregulation. In summary, we demonstrate that insulin downregulates HSD11B2 through increased LIP expression and augmented lactate secretion. Such mechanisms are of interest and potential significance for sodium reabsorption in the colon.

Postnatal persistent infection with classical Swine Fever virus and its immunological implications.

It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed. In addition to the epidemiological and economic significance of persistent CSFV infection, this model could be useful for understanding the mechanisms of viral persistence.

Children's Perceptions of Male and Female Athletes as Presented in Sports Illustrated for Kids

Despite gains made by Title IX in the past 36 years, including increased female participation in high school and collegiate sport, there is evidence that gender equity in sport is not fully achieved. Researchers target the media because they tend to shape social values and disseminate information to the masses (Kane, 1978, in Fink & Kensicki, 2002). As sports become more pervasive, framing theory has become particularly relevant. The purpose of this study is to build on the Hardin et al. (2002) study by examining the relationship among media sports coverage, gender equity in sport and the perceptions young sports fans begin to form about gender and sport based on media consumption. The researcher hypothesized that since women face discrimination in sport starting from the time that they choose to participate, children will perceive male athletes and their sports as more legitimate. Additionally, the media play a major role in shaping the views of audiences, so the way that they represent male and female athletes, including juxtaposing them, may have an impact on children. The researcher conducted a content analysis of 24 Sports Illustrated for Kids issues from 1996 to 1999 and 24 issues from 2006 to 2007. The researcher analyzed the content of photographs (N=3219) and of headlines (N=762) by using the definitions determined by Hardin et al. (2002). We found that there is a disproportionate amount of coverage devoted to male athletes and that the discrepancy between media representation between men and women in sport has grown since the mid-1990s. This study also includes a focus group conducted with three children from a community swimming program in a northeastern town and found that those children were acutely aware of the differences between men and women in sport based on the discussion. The researcher does not attempt to find a causal relationship between these children’s perceptions and the way media represents them, but rather uses the focus group to complement the content analysis. As children become sports consumers in later life, future research exploring the relationship between children’s perceptions and the media’s representations need to be done before causality and the significance of media effects are determined.

Validity and reliability of using MVP 4 Function Walk4Life digital pedometers to assess physical activity levels among preschool-aged Head Start children

The Surgeon General recommends preschoolers 3-5 years old accumulate 60 minutes of moderate-to-vigorous physical activity (MVPA) per day. However, there is limited data measuring physical activity (PA) and MVPA amongst this population. The purpose of this cross-sectional study is to determine the validity, reliability, and feasibility of using MVP 4 Function Walk4Life digital pedometers (MVP-4) in measuring MVPA among preschoolers using the newly modified direct observational technique, System for Observing Fitness Instruction Time-Preschool Version (SOFIT-P) as the gold standard. An ethnically diverse population of 3-5 year old underserved children were recruited from two Harris County Department of Education (HCDE) Head Start centers. For 2 days at baseline and 2 days at post-test, 75 children enrolled wore MVP-4 pedometers for approximately 6-hours per observation day and were observed using SOFIT-P during predominantly active times. Statistical analyses used Pearson "r" correlation coefficients to determine mean minutes of PA and MVPA, convergent and criterion validity, and reliability. Significance was set at p = <0.05. Feasibility was determined through process evaluation information collected during this study via observations from data collectors and teacher input. Results show mean minutes of PA and MVPA ranged between 30-42 and 11-14 minutes, respectively. Convergent validity comparing BMI percentiles with MVP-4 PA outcomes show no significance at pre-test; however, each measurement at post-test showed significance for MVPA (p = 0.0247, p = 0.0056), respectively. Criterion validity comparing percent MVPA time between SOFIT-P and MVP-4 pedometers was determined; however, results deemed insufficient due to inconsistency in observation times while using the newly developed SOFIT-P. Reliability measures show no significance at pre-test, yet show significant results for all PA outcomes at post-test (p = 0.001, p = 0.001, p = 0.0010, p = 0.003), respectively. Finally, MVP-4 pedometers lacked feasibility due to logistical barriers in design. Researchers feel the significant results at post-test are secondary to increased familiarity and more accurate placement of pedometers across time. Researchers suggest manufacturers of MVP-4 pedometers further modify the instrument for ease of use with this population, following which future studies ought to determine validity using objective measures or all-day direct observation techniques.^

Hormone therapy and physical activity as predictors of lung cancer risk and survival: The California Teachers Study

Cigarette smoking is responsible for the majority of lung cancer cases worldwide; however, a proportion of never smokers still develop lung cancer over their lifetime, prompting investigation into additional factors that may modify lung cancer incidence, as well as mortality. Although hormone therapy (HT), physical activity (PA), and lung cancer have been previously examined, the associations remain unclear. This study investigated exposure to HT and PA that may modulate underlying mechanisms of lung cancer etiology and progression among women by using existing, de-identified data from the California Teachers Study (CTS).^ The CTS cohort, established in 1995–1996, has 133,479 active and retired female teachers and administrators, recruited through the California State Teachers Retirement System, and followed annually for cancer diagnosis, death, and change of address. Each woman enrolled in the CTS returned a questionnaire covering a wide variety of issues related to cancer risk and women's health, including recent and past HT use and physical activity, as well as active and environmental cigarette smoke exposure. Complete data to assess the associations between HT and lung cancer risk and survival were available for 60,592 postmenopausal women. Between 1995 and 2007, 727 of these women were diagnosed with invasive lung cancer; 441 of these died. Complete data to assess the associations between PA and lung cancer risk and survival were available for 118,513 women. Between 1995 and 2007, 853 of these women were diagnosed with invasive lung cancer; 516 of these died.^ After careful adjustment for smoking habits and other potential confounders, no measure of HT use was associated with lung cancer risk; however, any HT use (vs. no use) was associated with a decrease in lung-cancer-specific mortality. Specifically, among women who only used estrogen (E-only), decreases in lung cancer mortality were seen for recent use, but not for former use; no association was observed for estrogen plus progestin (E+P). Furthermore, among former users of HT, a statistically significant decrease in lung cancer mortality was observed for E-only use within 5 years prior to baseline, but not for E-only use >5 years prior to baseline. Neither long-term recreational PA nor recent recreational PA alone were associated with lung cancer risk; however, among women with a BMI<25 and ever smokers, high long-term moderate+strenuous PA was associated with a decrease in lung cancer risk. Women with non-local disease showed a decrease in lung cancer mortality associated with increasing duration of strenuous long-term activity, and 1.50-3.00 h/wk/y of recent moderate or recent strenuous PA. Long-term moderate PA was associated with decreased lung cancer mortality in never smokers, whereas recent moderate PA was associated with increased lung cancer mortality in current smokers. ^ Placing our findings in the context of the current literature, HT does not appear to be associated with lung cancer risk and previous studies reporting a protective effect of HT use on lung cancer risk may be subject to residual confounding by smoking. Looking at our findings regarding PA overall, the evidence still remains inconclusive regarding whether or not physical activity influence lung cancer risk or mortality. Our results suggest that recreational PA may associated with decreased lung cancer risk among women with BMI<25 and ever smoking-women; however, residual confounding by smoking should be strongly considered. To our knowledge, this is the first study to investigate lifetime recreational PA and lung cancer mortality among women. Our results contribute to the growing body of knowledge regarding non-smoking-related risk factors for lung cancer incidence and mortality among women. Given the potential clinical and interventional significance, further study and validation of these findings is warranted.^

International comparison of wait times and quality of care: A pilot study

During the healthcare reform debate in the United States in 2009/2010, many health policy experts expressed a concern that expanding coverage would increase waiting times for patients to obtain care. Many complained that delays in obtaining care in turn would compromise the quality of healthcare in the United States. Using data from The Commonwealth Fund 2010 International Health Policy Survey in Eleven Countries, this study explored the relationship between wait times and quality of care, employing a wait time scale and several quality of care indicators present in the dataset. The impact of wait times on quality was assessed. Increased wait time was expected to reduce quality of care. However, this study found that wait times correlated with better health outcomes for some measures, and had no association with others. Since this is a pilot study and statistical significance was not achieved for any of the correlations, further research is needed to confirm and deepen the findings. However, if future studies confirm this finding, an emphasis on reducing wait times at the expense of other health system level performance variables may be inappropriate. ^