Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat.

Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2'-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned locomotion but not with the prevention of cocaine-induced sensitization.

Assisted reproductive technology and obstetric outcome in couples when the male partner has a chronic viral disease.

BACKGROUND Assisted reproductive technology (ART) with washed semen can achieve pregnancy with minimal risk of horizontal and vertical transmission of chronic viral diseases (CVD) such as human immunodeficiency virus (HIV), hepati- tis C virus (HCV) and hepatitis B virus (HBV) among serodiscordant couples. How- ever, few studies have been made of the use made by these couples of ARTs or of the obstetric results achieved. MATERIALS AND METHODS In this retrospective study, 93 men who were seropositive for HIV, HCV or HBV and who underwent assisted reproduction treatment at our centre (Hospital Universitario Virgen de las Nieves, Granada, Spain) were included. Washed semen was tested to detect viral particles. Non-infected women were tested before and after each treatment, as were the neonates at birth and after three months. RESULTS A total of 62 sperm samples were washed, and none were positive for the detec- tion of viral molecules. Semen samples from 34 HBV positive males were not washed since the female partner had immunity to hepatitis B. In total, 38 clinical pregnancies were achieved (22% per cycle and 40.9% per couple) out of 173 cycles initiated, and 28 births were achieved (16.2% per cycle and 30.1% per couple), producing 34 live births. The rate of multiple pregnancies was 21.4%. Obstetric and neonatal results were similar in the groups of couples studied. At follow-up, no seroconversion was detected in the women or neonates. CONCLUSION Sperm washing and intracytoplasmic sperm injection are shown to be a safe and effective option for reducing the risk of transmission or super infection in serodiscordant or concordant couples who wish to have a child. Pregnancies ob- tained by ART in couples when the male is CVD infected achieve good obstetric and neonatal results.

Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.

PURPOSE: Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS: A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS: Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION: Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.

Estimation of Aedes aegypti (Diptera: Culicidae) population size and adult male survival in an urban area in Panama

Traditional mosquito control strategies rely heavily on the use of chemical insecticides. However, concerns about the efficiency of traditional control methods, environmental impact and emerging pesticide resistance have highlighted the necessity for developing innovative tools for mosquito control. Some novel strategies, including release of insects carrying a dominant lethal gene (RIDL®), rely on the sustained release of modified male mosquitoes and therefore benefit from a thorough understanding of the biology of the male of the species. In this report we present the results of a mark-release-recapture study aimed at: (i) establishing the survival in the field of laboratory-reared, wild-type male Aedes aegypti and (b) estimating the size of the local adult Ae. aegypti population. The study took place in Panama, a country where recent increases in the incidence and severity of dengue cases have prompted health authorities to evaluate alternative strategies for vector control. Results suggest a life expectancy of 2.3 days for released male mosquitoes (confidence interval: 1.78-2.86). Overall, the male mosquito population was estimated at 58 males/ha (range 12-81 males/ha), which can be extrapolated to an average of 0.64 pupae/person for the study area. The practical implications of these results are discussed.

Positive feedback in the transition from sexual reproduction to parthenogenesis.

Understanding how new phenotypes evolve is challenging because intermediate stages in transitions from ancestral to derived phenotypes often remain elusive. Here we describe and evaluate a new mechanism facilitating the transition from sexual reproduction to parthenogenesis. In many sexually reproducing species, a small proportion of unfertilized eggs can hatch spontaneously ('tychoparthenogenesis') and develop into females. Using an analytical model, we show that if females are mate-limited, tychoparthenogenesis can result in the loss of males through a positive feedback mechanism whereby tychoparthenogenesis generates female-biased sex ratios and increasing mate limitation. As a result, the strength of selection for tychoparthenogenesis increases in concert with the proportion of tychoparthenogenetic offspring in the sexual population. We then tested the hypothesis that mate limitation selects for tychoparthenogenesis and generates female-biased sex ratios, using data from natural populations of sexually reproducing Timema stick insects. Across 41 populations, both the tychoparthenogenesis rates and the proportions of females increased exponentially as the density of individuals decreased, consistent with the idea that low densities of individuals result in mate limitation and selection for reproductive insurance through tychoparthenogenesis. Our model and data from Timema populations provide evidence for a simple mechanism through which parthenogenesis can evolve rapidly in a sexual population.

Development of a new tool for assessing health-related quality of life in patients with primary hyperparathyroidism.

BACKGROUND Several studies in recent years have evaluated Health Related Quality of Life (HRQoL) of patients with primary hyperparathyroidism (PHPT). No disease specific questionnaires are available to assess the impact of the disease. The aim of this research is to describe the development of a new disease specific Quality of Life (QoL) questionnaire for use specifically with PHPT patients. METHODS A conceptual model was developed describing the impact of the disease and its symptoms on QoL domains. A literature review was conducted to identify the most relevant domains. A focus group with experts was used to validate the domains; 24 patients were also interviewed to complement the information from the patient's perspective. A content analysis of the interviews was performed to identify items related with the impact of the disease, leading to PHPQoL-V.1 which was presented to a sample of 67 patients. Reliability was assessed by Cronbach's coefficient alpha and item-total score correlations. Validity was assessed by a factor analysis performed to determine the number of domains. Rasch analysis was carried out in order to refine the questionnaire items. RESULTS 259 items were extracted from the interviews that were subsequently reduced to 34 items. Cronbach's coefficient alpha was 0.92. The factor analysis extracted two domains (physical and emotional). After Rasch analysis the questionnaire PHPQoL-V.2 kept 16 items (9 physical and 7 emotional). The questionnaire was developed in a Spanish population and the final version was translated to English through translation and back-translation. CONCLUSION The first disease specific HRQoL questionnaire for PHPT patients (PHPQoL-16) has been developed. Validation studies designed to assess measurement properties of this tool are currently underway.

Should screening for Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-men who have sex with men be recommended?

INTRODUCTION Sexually transmitted infections (STI) like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been associated with increased risk of HIV acquisition (1). It has been also described as a high prevalence of asymptomatic CT and NG infections in men who have sex with men (MSM) (2). The aim of this study was to know the prevalence of CT and/or NG infections in asymptomatic HIV-MSM and the related factors. MATERIALS AND METHODS Prospective study of a cohort of asymptomatic HIV-MSM with follow-up in Malaga (southern Spain) during October 2012-May 2014. Patients with an opportunistic event or who received active antibiotic therapy for CT and/or NG in the previous month were excluded. All of them completed a questionnaire about sexual behaviour, barrier methods and recreational drugs use. Demographical, epidemiological, clinical, analytical and therapeutic data were also collected. Pharyngeal and rectal swabs, and urine samples were collected to be tested for CT and NG by nucleic acid amplification test (c4800 CT/NG. Roche Diagnostics, Mannheim, Germany) (3). STATISTICS ANALYSIS SPSS 17.0. RESULTS 255 patients were asked to participate and 248 of them accepted. Median age was 37.7 (30.6-46.3) years, median time since HIV diagnosis was 47.7 (10.5-104.1) months, and median CD4 cells count was 607 (440-824) cell/µL. There were 195 (78.6%) patients on antiretroviral therapy; 81.5% of them had undetectable viral load. 80.5% of the patients had a past history of STI. Infection by CT and/or NG was diagnosed in 24 (9.7%) patients. Overall four urine samples, two pharyngeal, and 15 rectal ones were positive for CT, and five pharyngeal and five rectal swabs were positive for NG. Two patients were co-infected by CT and NG: one with CT in urine and both in rectum, another with CT in urine and rectum and NG in pharynx. One patient presented CT in pharynx and rectum, and two patients NG in pharynx and rectum. Positive CT and/or NG tests were only related with detectable HIV viral load (OR 3.08, 95% CI 1.2-7.4; p=0.01). It was not related with sexual behaviour, nor with alcohol or recreational drugs use. CONCLUSIONS STI screening had a great acceptance in this population. There was a high prevalence of asymptomatic CT and/or NG infections. Rectum sample was the most effective one. Viral suppression could protect from these STI. Screening should be recommended in HIV-MSM.

Increased condom use without other major changes in sexual behavior among the general population in Switzerland.

The expression of DNA topoisomerase II alpha and beta genes was studied in murine normal tissues. Northern blot analysis using probes specific for the two genes showed that the patterns of expression were different among 22 tissues of adult mice. Expression levels of topoisomerase II alpha gene were high in proliferating tissues, such as bone marrow and spleen, and undetectable or low in 17 other tissues. In contrast, high or intermediate expression of topoisomerase II beta gene was found in a variety of tissues (15) of adult mice, including those with no proliferating cells. Topoisomerase II gene expression was also studied during murine development. In whole embryos both genes were expressed at higher levels in early than late stages of embryogenesis. Heart, brain and liver of embryos two days before delivery, and these same tissues plus lung and thymus of newborn (1-day-old) mice expressed appreciable levels of the two genes. Interestingly, a post-natal induction of the beta gene expression was observed in the brain but not in the liver; conversely, the expression of the alpha gene was increased 1 day after birth in the liver but not in the brain. However, gene expression of a proliferation-associated enzyme, thymidylate synthase, was similar in these tissues between embryos and newborns. Thus, the two genes were differentially regulated in the post-natal period, and a tissue-specific role may be suggested for the two isoenzymes in the development of differentiated tissues such as the brain and liver. Based on the differential patterns of expression of the two isoforms, this analysis indicates that topoisomerase II alpha may be a specific marker of cell proliferation, whereas topoisomerase II beta may be implicated in functions of DNA metabolism other than replication.

Adolescents health in Georgia: a national portrait.

The aim of the study was to assess the basic indicators of health of adolescents in Georgia. A self-administered anonymous questionnaire was adapted from the Swiss Survey (SMASH2002), translated into Georgian and other languages mainly used in schools (Russian, Armenian and Azeri). It contained 87 questions. Two-stage cluster sampling was devised. Weight was adjusted. A total of 599 classes were selected. All questionnaires before being processed into the Epidata (www.epidata.dk) were edited. The final data were analysed by SPSS 11.0. General health status was considered as excellent and very good by 34.0+/-0.8% of respondents. 21.5% claimed to never miss the school due to the illness. The frequencies of physical disability and chronic diseases were 8.0% and 5.0% correspondingly. Among health-related problems the most frequent are problems with teeth, headache and acne. 5.9% of girls had some kind of gynecological problems quite often and very often. Performed survey is a first one done among adolescents in Georgia. It gave us basic information for planning and implementation of necessary measures in order to improve the health of adolescents and raise awareness of professionals involved in health care and prevention settings for adolescents. The data can be also used for monitoring of health status of adolescents in Georgia.

The role of polymerase chain reaction of high-risk human papilloma virus in the screening of high-grade squamous intraepithelial lesions in the anal mucosa of human immunodeficiency virus-positive males having sex with males.

OBJECTIVES To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM). METHODS This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation. RESULTS Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82). CONCLUSIONS When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV-positive patients. HPV suppression with treatment protects against the appearance of HSIL.

Oral and general health-related quality of life in patients treated for oral cancer compared to control group.

BACKGROUND Health-related quality of life (HRQoL) is gaining importance as a valuable outcome measure in oral cancer area. The aim of this study was to assess the general and oral HRQoL of oral and oropharyngeal cancer patients 6 or more months after treatment and compare them with a population free from this disease. METHODS A cross-sectional study was carried out with patients treated for oral cancer at least 6 months post-treatment and a gender and age group matched control group. HRQoL was measured with the 12-Item Short Form Health Survey (SF-12); oral HRQoL (OHRQoL) was evaluated using the Oral Health Impact Profile (OHIP-14) and the Oral Impacts on Daily Performances (OIDP). Multivariable regression models assessed the association between the outcomes (SF-12, OHIP-14 and OIDP) and the exposure (patients versus controls), adjusting for sex, age, social class, functional tooth units and presence of illness. RESULTS For patients (n = 142) and controls (n = 142), 64.1% were males. The mean age was 65.2 (standard deviation (sd): 12.9) years in patients and 67.5 (sd: 13.7) years in controls. Patients had worse SF-12 Physical Component Summary scores than controls even in fully the adjusted model [β-coefficient = -0.11 (95% CI: -5.12-(-0.16)]. The differences in SF-12 Mental Component Summary were not statistically significant. Regarding OHRQoL patients had 11.63 (95% CI: 6.77-20.01) higher odds for the OHIP-14 and 21.26 (95% CI: 11.54-39.13) higher odds for OIDP of being in a worse category of OHRQoL compared to controls in the fully adjusted model. CONCLUSION At least 6 months after treatment, oral cancer patients had worse OHRQoL, worse physical HRQoL and similar psychological HRQoL than the general population.

Are the health messages in schoolbooks based on scientific evidence? A descriptive study.

BACKGROUND Most textbooks contains messages relating to health. This profuse information requires analysis with regards to the quality of such information. The objective was to identify the scientific evidence on which the health messages in textbooks are based. METHODS The degree of evidence on which such messages are based was identified and the messages were subsequently classified into three categories: Messages with high, medium or low levels of evidence; Messages with an unknown level of evidence; and Messages with no known evidence. RESULTS 844 messages were studied. Of this total, 61% were classified as messages with an unknown level of evidence. Less than 15% fell into the category where the level of evidence was known and less than 6% were classified as possessing high levels of evidence. More than 70% of the messages relating to "Balanced Diets and Malnutrition", "Food Hygiene", "Tobacco", "Sexual behaviour and AIDS" and "Rest and ergonomics" are based on an unknown level of evidence. "Oral health" registered the highest percentage of messages based on a high level of evidence (37.5%), followed by "Pregnancy and newly born infants" (35%). Of the total, 24.6% are not based on any known evidence. Two of the messages appeared to contravene known evidence. CONCLUSION Many of the messages included in school textbooks are not based on scientific evidence. Standards must be established to facilitate the production of texts that include messages that are based on the best available evidence and which can improve children's health more effectively.

Sexual dimorphism of the human mandible: demonstration by elliptical Fourier analysis.

A new quantitative approach of the mandibular sexual dimorphism, based on computer-aided image analysis and elliptical Fourier analysis of the mandibular outline in lateral view is presented. This method was applied to a series of 117 dentulous mandibles from 69 male and 48 female individuals native of Rhenish countries. Statistical discriminant analysis of the elliptical Fourier harmonics allowed the demonstration of a significant sexual dimorphism in 97.1% of males and 91.7% of females, i.e. in a higher proportion than in previous studies using classical metrical approaches. This original method opens interesting perspectives for increasing the accuracy of sex identification in current anthropological practice and in forensic procedures.

Ageing prisoners' health care: analysing the legal settings in Europe and the United States.

BACKGROUND: Relatively little is known about the current health care situation and the legal rights of ageing prisoners worldwide. To date, only a few studies have investigated their rights to health care. However, elderly prisoners need special attention. OBJECTIVE: The aim of this article is to critically review the health care situation of older prisoners by analysing the relevant national and international legal frameworks with a particular focus on Switzerland, England and Wales, and the United States (U.S.). METHODS: Publications on legal frameworks were searched using Web of Science, PubMed, MEDLINE, HeinOnline, and the National Criminal Justice Reference Service. Searches utilizing combinations of keywords relating to ageing prisoners were performed. Relevant reports and policy documents were obtained in order to understand the legal settings in Switzerland, England and Wales, and the U.S. All articles, reports, and policy documents published in English and German between 1774 to June 2012 were included for analysis. Using a comparative approach, an outline was completed to distinguish positive policies in this area. Regulatory approaches were investigated through evaluations of soft laws applicable in Europe and U.S. Supreme Court judgements. RESULTS: Even though several documents could be interpreted as guaranteeing adequate health care for ageing prisoners, there is no specific regulation that addresses this issue completely. The Vienna International Plan of Action on Ageing contributes the most by providing an in-depth analysis of the health care needs of older persons. Still, critical analysis of retrieved documents reveals the lack of specific legislation regarding the health care for ageing prisoners. CONCLUSION: No consistent regulation delineates the provision of health care for ageing prisoners. Neither national nor international institutions have enforceable laws that secure the precarious situation of older adults in prisons. To initiate a change, this work presents critical issues that must be addressed to protect the right to health care and well-being of ageing prisoners. Additionally, it is important to design legal structures and guidelines which acknowledge and accommodate the needs of ageing prisoners.

Effectiveness of a pediatric palliative home care team as experienced by parents and health care professionals.

OBJECTIVES: Little data are available on palliative home care for children. The objective of this study was to evaluate the effectiveness of a specialized pediatric palliative home care team (PPHCT) as experienced by parents and health care professionals (HCPs). METHODS: Parents and HCPs involved in the care of terminally ill children who died and whom the PPHCT was in charge of were surveyed with questionnaires focusing on satisfaction with the PPHCT, satisfaction with the course of the dying phase, and the development of anxiety, depression, and prolonged grief disorder. RESULTS: Forty-three parent dyads participated (return rate, 88%). Satisfaction with the PPHCT scored a median of 10 (numeric rating scale, 0-10). The child's death was predominantly experienced as very peaceful (median, 9); 71% died at home. According to parents, involvement of the PPHCT led to highly significant (p<0.001) improvements in the children's symptoms and quality of life, as well as in aspects of communication and administrative barrier reduction. Anxiety was detected in 25% of parents, depression in 19%, and prolonged grief disorder in 13%. HCPs (return rate, 83%) evaluated all investigated care domains (particularly cooperation/communication/family support) as being significantly improved (p<0.001). Thirty-five percent of HCPs felt uncertain concerning pediatric palliative care; 79% would welcome specific training opportunities. CONCLUSIONS: Involvement of a PPHCT is experienced as a substantial improvement of care by parents and HCPs. Coordination of palliative care during the last phase of life appears to be an important quality factor for the home care of dying children and their families.