An impaired mitochondrial electron transport chain increases retention of the hypoxia imaging agent diacetylbis(4-methylthiosemicarbazonato)copper II

Radiolabeled diacetylbis(4-methylthiosemicarbazonato)copper^II [Cu^II(atsm)] is an effective positron-emission tomography imaging agent for myocardial ischemia, hypoxic tumors, and brain disorders with regionalized oxidative stress, such as mitochondrial myopathy, encephalopathy, and lactic acidosis with stroke-like episodes (MELAS) and Parkinson’s disease. An excessively elevated reductive state is common to these conditions and has been proposed as an important mechanism affecting cellular retention of Cu from Cu^II(atsm). However, data from whole-cell models to demonstrate this mechanism have not yet been provided. The present study used a unique cell culture model, mitochondrial xenocybrids, to provide whole-cell mechanistic data on cellular retention of Cu from Cu^II(atsm). Genetic incompatibility between nuclear and mitochondrial encoded subunits of the mitochondrial electron transport chain (ETC) in xenocybrid cells compromises normal function of the ETC. As a consequence of this impairment to the ETC we show xenocybrid cells upregulate glycolytic ATP production and accumulate NADH. Compared to control cells the xenocybrid cells retained more Cu after being treated with Cu^II(atsm). By transfecting the cells with a metal-responsive element reporter construct the increase in Cu retention was shown to involve a Cu^II(atsm)-induced increase in intracellular bioavailable Cu specifically within the xenocybrid cells. Parallel experiments using cells grown under hypoxic conditions confirmed that a compromised ETC and elevated NADH levels contribute to increased cellular retention of Cu from CuII(atsm). Using these cell culture models our data demonstrate that compromised ETC function, due to the absence of O2 as the terminal electron acceptor or dysfunction of individual components of the ETC, is an important determinant in driving the intracellular dissociation of Cu^II(atsm) that increases cellular retention of the Cu.

Modification of the National Inpatient Medication Chart improves venous thromboembolism prophylaxis rates in high-risk medical patients

Background : Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality in Australia. While there is well-established evidence for the use of VTE prophylaxis in hospital inpatients, adherence to such guidelines is poor. Aim : The aim of the present study is to assess the impact of education and system change on improving rates of VTE prophylaxis in hospital inpatients. Methods : We performed four consecutive audits of inpatient medical records of a regional hospital service over 2 years. The audits aimed to test the impact of serial interventions at increasing the appropriate use of VTE prophylaxis (based on risk assessment). The interventions were (i) staff education and (ii) a process change that mandated a prophylaxis decision by modifying the National Inpatient Medication Chart with ‘VTE avoidance’ preprinted in the first medication box. Results : Our results from the baseline study showed that of the 236 medical inpatients reviewed, 80% were at high risk of VTE. Of this high-risk cohort, 34.9% (confidence interval (CI) 28–42%) had appropriate prophylaxis decisions. Post the education intervention, 43.2% (CI 37–49%) of the high-risk cohort received appropriate VTE prophylaxis, an improvement of 8.3% (CI −1% to 18%) from baseline. With the subsequent introduction of a process change, 82.1% (CI 66–92%) of the high-risk cohort received appropriate prophylaxis, an improvement of 47.2% and 38.8% (CI 24–54%) when compared with baseline and education respectively. Retention rates at 11 months postsystem change were 73% (CI 55–86%). Conclusions : This study therefore concluded that while education has an impact on rates of appropriate VTE prophylaxis, it is system change that has the most marked and sustained effect.

Obsessive-compulsive disorder and personality disorder - Evidence from the British National Survey of Psychiatric Morbidity 2000

Background Previous studies indicate that most individuals with obsessive-compulsive disorder (OCD) have comorbid personality disorders (PDs), particularly from the anxious cluster. However, the nature and strength of this association remains unclear, as the majority of previous studies have relied heavily on clinical populations. We analysed the prevalence of screen positive personality disorder in a representative sample of adults with OCD living in private households in the UK. Methods A secondary analysis of data from the 2000 British National Survey of Psychiatric Morbidity. The prevalence of PD, as determined by the SCID-II questionnaire, was compared in participants with OCD, with other neuroses and non-neurotic controls. Within the OCD group we also analysed possible differences relating to sex and subtypes of the disorder. Results the prevalence of any screen positive PD in the OCD group (N = 108) was 74%, significantly greater than in both control groups. The most common screen positive categories were paranoid, obsessive-compulsive, avoidant, schizoid and schizotypal. Compared to participants with other neuroses, OCD cases were more likely to screen positively for paranoid, avoidant, schizotypal, dependent and narcissistic PDs. Men with OCD were more likely to screen positively for PDs in general, cluster A PDs, antisocial, obsessive-compulsive and narcissistic categories. The presence of comorbid neuroses in people with OCD had no significant effect on the prevalence of PD. Conclusions Personality pathology is highly prevalent among people with OCD who are living in the community and should be routinely assessed, as it may affect help-seeking behaviour and response to treatment.

Where do Latin America and the Caribbean stand in relation to the eLAC2007 Plan of Action?: evidence from available information

Includes bibliography

Summary report of the Caribbean meeting of experts on Implementation of the SIDS Plan of Action

The Caribbean Meeting of Experts on Implementation of the SIDS Programme of Action, held at the Holiday Inn Hotel, Port of Spain, Trinidad and Tobago, 17-19 May 1995 was convened to review progress towards implementation of the SIDS Programme of Action (SIDS-POA), to discuss constraints on the effective implementation of the Programme and to agree on priority areas for action. It was organized by the Economic Commission for Latin America and the Caribbean/Caribbean Development and Cooperation Committee (ECLAC/CDCC), in collaboration with the United Nations Development Programme’s Special Unit for Technical Cooperation among Developing Countries (UNDP/TCDC), the United Nations Environment Programme (UNEP), the University of the West Indies Centre for Environment and Development (UWICED), and the Caribbean Community (CARICOM). A copy of the programme and a list of documents are attached to this report as Annex I and II respectively.

Reforma agrária na Amazônia?: avaliação do II Plano Nacional de Reforma Agrária no território rural do Baixo Tocantins – PA

Esta pesquisa teve como objetivo principal fazer uma avaliação do Programa Novos Assentamentos contido no II Plano Nacional de Reforma Agrária. O recorte espacial foi o Território Rural do Baixo Tocantins a partir do Assentamento Araxiteua, localizado no município do Acará – nordeste do Estado do Pará. Foi utilizada a metodologia de métodos mistos. Esse estudo focalizou a aplicação de questionários com 80 chefes de famílias que foram entrevistadas com a técnica de pesquisas não estruturadas com um técnico do INCRA, o Presidente do Conselho Municipal de Desenvolvimento Rural Sustentável do Acará, um representante do Departamento de Educação do Campo desse município, o Presidente da Associação dos Assentados do Assentamento Araxiteua e alguns chefes de famílias. O recorte temporal da pesquisa foi de 2006 a 2011. Os resultados demonstram que os impactos foram mais positivos do que negativos. O impacto negativo foi mensurado a partir da variável social. As variáveis social, territorial e econômica resultaram em uma melhoria na renda e na qualidade de vida dos assentados. Destacam-se como negativos a não aplicação da assistência técnica, a não aplicação do PRONERA e não liberação do crédito apoio mulher. Como positivos, a liberação e aplicação do crédito inicial, a introdução da rede de energia elétrica e a facilidade do acesso ao PRONAF. Conclui-se que o II Plano Nacional de Reforma Agrária cumpriu uma parcela significativa dos seus objetivos.

Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.

Angiotensin II type 2 receptor (AT2R) is associated with increased tolerance of the hyperthyroid heart to ischemia-reperfusion

Background Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against Ischemia/Reperfusion (I/R) injury. Type 2 Angiotensin II receptors (AT2R) are shown to be upregulated in cardiac hypertrophy observed in hyperthyroidism and this receptor has been reported to mediate cardioprotection against ischemic injury. Methods The aim of the present study was to evaluate the role of AT2R in the recovery of myocardium after I/R in isolated hearts from T3 treated rats. MaleWistar rats were treated with triiodothyronine (T3; 7 μg/100 gBW/day, i.p.) in the presence or not of a specific AT2R blocker (PD123,319; 10 mg/Kg) for 14 days, while normal rats served as control. After treatment, isolated hearts were perfused in Langendorff mode; after 30 min of stabilization, hearts were subjected to 20 min of zero-flow global ischemia followed by 25 min, 35 min and 45 min of reperfusion. Results T3 treatment induced cardiac hypertrophy, which was not changed by PD treatment. Post-ischemic recovery of cardiac function was increased in T3-treated hearts after 35 min and 45 min of reperfusion as compared to control and the ischemic contracture was accelerated and intensified. AT2R blockade was able to return the evaluated functional parameters of cardiac performance (LVDP, +dP/dtmáx and −dP/dtmin) to the control condition. Furthermore, AT2R blockade prevented the increase in AMPK expression levels induced by T3, suggesting its possible involvement in this process. Conclusion AT2R plays a significant role in T3-induced cardioprotection.

Opportunities and risks in reconciling conservation and development in a post-Soviet setting: The example of the Tajik National Park

In the Tajik National Park (TNP) - a high-altitude area of nearly 26,000 km2 in Central Asia - past and present human activities visibly contrast with standard conservation requirements for protected areas worldwide. This paper focuses on resource management, and highlights three major processes that threaten both the sustainable use of natural resources and the preservation of nature per se: (i) intensified use of biomass as a fuel resource, (ii) inappropriate pasture management, and (iii) increased pressure on endangered wildlife. From analysis of these processes - their historical background, root causes, trends and interrelationships - options and needs to improve park management are proposed and discussed.

Implementing the Global Plan of Action on workers' health: Components to protect health care workers

Health care workers are at risk for percutaneous injuries and infection with blood born pathogens due to needle stick injuries with contaminated needles. The most common pathogens transmitted are hepatitis B, and C and HIV/AIDS. According to the WHO Global Plan of Action (GPA) a large gap exist between and within countries with regards to the health status of workers and their exposure to occupational risk. Less than 15% of the world's work forces have access to occupational health services despite the availability of effective interventions that can prevent occupational hazards, or protect and promote health in the workplace. The 2006 World Health Report declared that there is a global crisis in the health care work force. 1 in 400 of the world's health care workers work in Sub-Saharan Africa. 1 in 3 work in the U.S or Canada. The shortage of health care workers is worst in Southeast Asia and Sub-Saharan Africa. These countries have the highest burden of exposure to contaminated sharps. They rarely, if ever monitor the exposure or health impact of occupational ailments and injuries on workers. Many injuries are unreported. Occupational health services in the developing world are virtually non existent. Many health care workers leave their home countries and go to work in other countries where the working conditions, occupational services included, are better. The inability of countries to provide the necessary numbers of health care workers to provide a high level of health coverage is a threat to national and international public health security. Immunizing health care workers against hepatitis B and providing them PEP, PPE, education and safety training is an essential part of increasing and maintaining the numbers of health care workers in the critical shortage areas. ^

Compilation of scientific results of the OASIS project

Seamounts are of great interest to science, industry and conservation because of their potential role as 'stirring rods' of the oceans, their enhanced productivity, their high local biodiversity, and the growing exploitation of their natural resources. This is accompanied by rising concern about the threats to seamount ecosystems, e.g. through over-fishing and the impact of trawling. OASIS described the functioning characteristics of seamount ecosystems. OASIS' integrated hydrographic, biogeochemical and biological information. Based on two case studies. The scientific results, condensed in conceptual and mass balanced ecosystem models, were applied to outline a model management plan as well as site-specific management plans for the seamounts investigated. OASIS addressed five main objectives: Objective 1: To identify and describe the physical forcing mechanisms effecting seamount systems Objective 2: To assess the origin, quality and dynamics of particulate organic material within the water column and surface sediment at seamounts. Objective 3: To describe aspects of the biodiversity and the ecology of seamount biota, to assess their dynamics and the maintenance of their production. Objective 4: Modelling the trophic ecology of seamount ecosystems. Objective 5: Application of scientific knowledge to practical conservation.

Annotated record of the detailed examination of Mn deposits from SAFARI II cruise stations

The cores and dredges described at this site were taken on the SAFARI II cruise from 21 July until 1 September 1981 by the MusÈum National d'Histoire Naturelle from the R/V Marion Dufresne. A total of 65 cores, dredges and camera stations were recovered and are available at MNHN for sampling and study.

Specific interaction of the yeast cis-Golgi syntaxin Sed5p and the coat protein complex II component Sec24p of endoplasmic reticulum-derived transport vesicles

The generation of transport vesicles at the endoplasmic reticulum (ER) depends on cytosolic proteins, which, in the form of subcomplexes (Sec23p/Sec24p; Sec13p/Sec31p) are recruited to the ER membrane by GTP-bound Sar1p and form the coat protein complex II (COPII). Using affinity chromatography and two-hybrid analyses, we found that the essential COPII component Sec24p, but not Sec23p, binds to the cis-Golgi syntaxin Sed5p. Sec24p/Sed5p interaction in vitro was not dependent on the presence of [Sar1p⋅GTP]. The binding of Sec24p to Sed5p is specific; none of the other seven yeast syntaxins bound to this COPII component. Whereas the interaction site of Sec23p is within the N-terminal half of the 926-aa-long Sec24p (amino acid residues 56–549), Sed5p binds to the N- and C-terminal halves of the protein. Destruction by mutagenesis of a potential zinc finger within the N-terminal half of Sec24p led to a nonfunctional protein that was still able to bind Sec23p and Sed5p. Sec24p/Sed5p binding might be relevant for cargo selection during transport-vesicle formation and/or for vesicle targeting to the cis-Golgi.