Intoxication, criminal offences and suicide attempts in a group of South African problem drinkers

Background. Incidence rates of crime and alcohol abuse in South Africa are unacceptably high. Research suggests a relationship between alcohol and both crime and suicide. This study aims to add to the information base on this topic in South Africa.Methods. This is a cross-sectional record study of criminal offences and suicide attempts in 269 admissions to an alcohol rehabilitation unit in the Western Cape. Types of criminal offences and suicide attempts are described. Relationships are sought between crime, violent crime and suicide attempts on the one hand, and demographic and alcohol-related variables on the other.Results. One hundred and four subjects (39%) had criminal convictions, the majority of which were committed while the subjects were intoxicated. The commonest alcoholrelated crimes were driving-related (17% of subjects) and crimes of violence (15%). Male gender, younger age at initiation of drinking, and earlier onset of problem drinking were significantly associated with criminal behaviour. Violent crime was associated with earlier onset of initial, regular and problem drinking, and maternal alcohol abuse. Suicide attempts (24% of subjects) were associated with female gender, white racial group, not being in a marital relationship, younger current age and early age of problem drinking.Conclusions. There was an association between intoxication and both violent crime and suicide attempts. The importance of population studies and the need for intervention programmes aimed at teenagers who are drinking, are emphasised

Identification and Quantification of Metabolites in a Human Plasma Standard Reference Material by Multiple Mass Spectrometry Methods

peer reviewe

Amphetamine-type stimulant use and HIV/STI risk behaviour among young female sex workers in Phnom Penh, Cambodia

Background: Use of amphetamine-type substances (ATS) has been linked to increased risk of HIV and other sexually transmitted infections (STI) worldwide. In Cambodia, recent ATS use is independently associated with incident STI infection among young female sex workers (FSW). Methods: We conducted 33 in-depth interviews with women (15-29 years old) engaged in sex work to explore ATS use and vulnerability to HIV/STI. Results: Participants reported that ATS, primarily methamphetamine in pill and crystalline forms (yama), were cheap, widely available and commonly used. Yama was described as a “power drug” (thnam kamlang) which enabled women to work long hours and serve more customers. Use of ATS by clients was also common, with some providing drugs for women and/or encouraging their use, often resulting in prolonged sexual activity. Requests for unprotected sex were also more common among intoxicated clients and strategies typically employed to negotiate condom use were less effective. Conclusion: ATS use was highly functional for young women engaged in sex work, facilitating a sense of power and agency and highlighting the occupational significance and normalization of ATS in this setting. This highly gendered dynamic supports the limited but emerging literature on women's use of ATS, which to date has been heavily focused on men. Results indicate an urgent need to increase awareness of the risks associated with ATS use, to provide women with alternative and sustainable options for income generation, to better regulate the conditions of sex work, and to work with FSWs and their clients to develop and promote culturally appropriate harm reduction interventions. Keywords: sex work; amphetamine-type substances; HIV; sexually transmitted infections; risk behaviour; vulnerabilityNI

Intracellular signaling in key pathways is induced by treatment with ultrasound and microbubbles in a leukemia cell line, but not in healthy peripheral blood mononuclear cells

Treatment with ultrasound and microbubbles (sonoporation) to enhance therapeutic efficacy in cancer therapy is rapidly expanding, but there is still very little consensus as to why it works. Despite the original assumption that pore formation in the cell membrane is responsible for increased uptake of drugs, the molecular mechanisms behind this phenomenon are largely unknown. We treated cancer cells (MOLM-13) and healthy peripheral blood mononuclear cells (PBMCs) with ultrasound at three acoustic intensities (74, 501, 2079 mW/cm2) ± microbubbles. We subsequently monitored the intracellular response of a number of key signaling pathways using flow cytometry or western blotting 5 min, 30 min and 2 h post-treatment. This was complemented by studies on uptake of a cell impermeable dye (calcein) and investigations of cell viability (cell count, Hoechst staining and colony forming assay). Ultrasound + microbubbles resulted in both early changes (p38 (Arcsinh ratio at high ultrasound + microbubbles: +0.5), ERK1/2 (+0.7), CREB (+1.3), STAT3 (+0.7) and AKT (+0.5)) and late changes (ribosomal protein S6 (Arcsinh ratio at low ultrasound: +0.6) and eIF2α in protein phosphorylation). Observed changes in protein phosphorylation corresponded to changes in sonoporation efficiency and in viability, predominantly in cancer cells. Sonoporation induced protein phosphorylation in healthy cells was pronounced (p38 (+0.03), ERK1/2 (−0.03), CREB (+0.0), STAT3 (−0.1) and AKT (+0.04) and S6 (+0.2)). This supports the hypothesis that sonoporation may enhance therapeutic efficacy of cancer treatment, without causing damage to healthy cells.publishedVersio

Humanized Ovarian Cancer Patient-Derived Xenografts for Improved Preclinical Evaluation of Immunotherapies

High-grade serous ovarian cancer (HGSOC) has poor prognosis and new treatment modalities are needed. Immunotherapy, with checkpoint inhibitors, have demonstrated limited impact. To evaluate the suitability for immunotherapeutics, contextualized preclinical models are required to secure meaningful clinical translation. Therefore, we developed and characterized humanized patient-derived xenograft (hu PDX) murine models of HGSOC, which were established by orthotopic implantation of tumor cell suspensions and intravenous injection of CD34+ cells isolated from umbilical cord blood samples. The developing human immune system in NSG and NSGS mice was followed longitudinally by flow cytometry and characterized by mass cytometry with a panel of 34 surface markers. Molecular imaging of tumor burden, survival analysis, and characterization of tumor-infiltrating immune cells was performed to assess the treatment response to anti-PD-1 (nivolumab) monotherapy. Successful generation of hu PDX models was achieved. Mice treated with nivolumab showed a decrease in tumor burden, however no significant survival benefit was identified when compared to untreated controls. No correlation was seen between PD-L1 expression and CD8 T cell infiltration and response parameters. As the characterization showed an immune infiltration of predominantly myeloid cells, similar to what is observed in HGSOC patients, the models may have the potential to evaluate the importance of myeloid cell immunomodulation as well.publishedVersio

OS FATORES AMBIENTAIS E SUA RELAÇÃO COM O BAIXO PESO AO NASCER NO EXTREMO SUL DO BRASIL

<!-- /* Font Definitions */ @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-1610611985 1107304683 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:PT-BR; mso-fareast-language:PT-BR;} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:10.0pt; mso-ansi-font-size:10.0pt; mso-bidi-font-size:10.0pt;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> The study of cases and check-ups performed in Rio Grande county/RS, aimed to evaluate Low Birth Weight (LBW) in newborns of mothers residing near the industrial section in the town, and thought to be exposed to environmental pollution. 547 mothers who gave birth in hospital maternity units were interviewed between April and November 2003. The sample was made up of 138 cases and 409 check-ups. The results show that the location of the mothers residence in the area in question showed a greater odds ratio to LBW both in the bivaried analysis (RO 1.87; IC95 % 0.95-3.66) and the multivaried analysis (RO=4.67; IC95 % 0.95-22.90), but the p values were closer to the established cut off point (p=0.067 and p=0.057, respectively). Thus a relation between exposure to pollutants and LBW is shown, although additional studies are needed to clarify this issue area. These results show that it is important for health care workers, and especially by nurses, to take into account environmental issues regarding planning, development and prenatal care of pregnant women, as well as extended assistance to their children after birth.Esta investigación  de casos y controles, realizada en el municipio de  Rio Grande/RS, tuvo como objetivo evaluar el bajo peso al nacer (BPN) en recién-nacidos de madres que viven en las proximidades del área industrial de esta ciudad, consideradas más expuestas a la polución ambiental. Participaron de la encuesta  547 madres que alumbraron en las maternidades en los meses de abril a noviembre de 2003.  La muestra estuvo compuesta de 138 casos y 409 controles. Los resultados muestran que el lugar de la vivienda materna en el área expuesta presentó razones de odds mayores para BPN tanto en el análisis bivariado (RO 1,87; IC95% 0,95-3,66), cuanto en el análisis multivariado  (RO= 4,67; IC95% 0,95-22,90), pero los valores de p ubicándose mucho cerca del punto de corte establecido  (p=0,067 e p=0,057, respectivamente). De esta forma, se ve que hay una relación entre la exposición a contaminantes y BPN, pero son necesarios otros estudios para poder responder a esta cuestión con más claridad. Esos resultados muestran la necesidad de que la influencia ambiental sea considerada por parte de todo el grupo de salud, y por el enfermero en especial, tanto en lo que se refiere al planeamiento, desarrollo y acompañamiento  pre-natal  de las gestantes, como también, en el seguimiento de la asistencia a sus niños después del nacimiento  Este estudo de casos e controles, realizado no município de Rio Grande/RS, teve como objetivo avaliar o baixo peso ao nascer (BPN) em recém-nascidos de mães residentes nas proximidades da área industrial deste município, consideradas mais expostas à poluição ambiental. Foram entrevistadas 547 mães que deram à luz nas maternidades do município, durante os meses de abril a novembro de 2003. A amostra foi composta por 138 casos e 409 controles. Os resultados mostram que o local da residência materna na área exposta apresentou razões de odds maiores para BPN tanto na análise bivariada (RO 1,87; IC95% 0,95-3,66), quanto na análise multivariada (RO= 4,67; IC95% 0,95-22,90), mas os valores de p situaram-se muito próximos ao ponto de corte estabelecido (p=0,067 e p=0,057, respectivamente). Desta maneira, esboça-se uma relação entre exposição a poluentes e BPN, mas são necessários outros estudos  para poder responder a esta questão com maior clareza. Esses resultados mostram a necessidade de que a influência ambiental seja considerada por parte de toda a equipe de saúde, e pelo enfermeiro em especial, tanto no que se refere ao planejamento, desenvolvimento e acompanhamento pré-natal das gestantes, como também, no seguimento da assistência de suas crianças, após o nascimento. &nbsp

Selling sex in unsafe spaces: Sex work risk environments in Phnom Penh, Cambodia

Background The risk environment framework provides a valuable but under-utilised heuristic for understanding environmental vulnerability to HIV and other sexually transmitted infections among female sex workers. Brothels have been shown to be safer than street-based sex work, with higher rates of consistent condom use and lower HIV prevalence. While entertainment venues are also assumed to be safer than street-based sex work, few studies have examined environmental influences on vulnerability to HIV in this context. Methods As part of the Young Women's Health Study, a prospective observational study of young women (15-29 years) engaged in sex work in Phnom Penh, we conducted in-depth interviews (n = 33) to explore vulnerability to HIV/STI and related harms. Interviews were conducted in Khmer by trained interviewers, transcribed and translated into English and analysed for thematic content. Results The intensification of anti-prostitution and anti-trafficking efforts in Cambodia has increased the number of women working in entertainment venues and on the street. Our results confirm that street-based sex work places women at risk of HIV/STI infection and identify significant environmental risks related to entertainment-based sex work, including limited access to condoms and alcohol-related intoxication. Our data also indicate that exposure to violence and interactions with the police are mediated by the settings in which sex is sold. In particular, transacting sex in environments such as guest houses where there is little or no oversight in the form of peer or managerial support or protection, may increase vulnerability to HIV/STI. Conclusions Entertainment venues may also provide a high risk environment for sex work. Our results indicate that strategies designed to address HIV prevention among brothel-based FSWs in Cambodia have not translated well to street and entertainment-based sex work venues in which increasing numbers of women are working. There is an urgent need for targeted interventions, supported by legal and policy reforms, designed to reduce the environmental risks of sex work in these settings. Future research should seek to investigate sex work venues as risk environments, explore the role of different business models in mediating these environments, and identify and quantify exposure to risk in different occupational settings. Keywords: sex work; risk; environment; vulnerability; HIV; STI; young women; entertainment; Cambodi

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Quality and effectiveness of different approaches to primary care delivery in Brazil

BACKGROUND: Since 1994, Brazil has developed a primary care system based on multidisciplinary teams which include not only a physician and a nurse, but also 4–6 lay community health workers. This system now consists of 26,650 teams, covering 46% of the Brazilian population. Yet relatively few investigations have examined its effectiveness, especially in contrast with that of the traditional multi-specialty physician team approach it is replacing, or that of other existing family medicine approaches placing less emphasis on lay community health workers. Primary health care can be defined through its domains of access to first contact, continuity, coordination, comprehensiveness, community orientation and family orientation. These attributes can be ascertained via instruments such as the Primary Care Assessment Tool (PCATool), and correlated with the effectiveness of care. The objectives of our study are to validate the adult version of this instrument in Portuguese, identify the extent (quality) of primary care present in different models of primary care services, and correlate this extent with measures of process and outcomes in patients with diabetes, hypertension and coronary heart disease (CHD). METHODS/DESIGN: We are conducting a population-based cross-sectional study of primary care in the municipality of Porto Alegre. We will interview a random sample totaling 3000 adults residing in geographic areas covered by four distinct models of primary care of the Brazilian national health system or, alternatively, by one nationally prominent complementary health care service, as well as the physicians and nurses of the health teams of these services. Interviews query perceived quality of care (PCATool-Adult Version), patient satisfaction, and process indicators of management of diabetes, hypertension and known CHD. We are measuring blood pressure, anthropometrics and, in adults with known diabetes, glycated hemoglobin. DISCUSSION: We hope to contribute not only by validating the PCATool-Adult Version for use in Brazil, but also by furnishing ample data concerning the appropriate mix of health care professionals in the primary care team, a question of international import. Once validated, future use of this instrument should help direct advances aiming at improving the quality of primary care in Brazil