Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study

BACKGROUND Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study. METHODS Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models. FINDINGS Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p<0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p<0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p<0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p<0·0001). INTERPRETATION Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe. FUNDING EU Seventh Framework Programme.

Tobacco use and related psychosocial risk factors among youth in urban India: Assessment of Project MYTRI follow-up surveys

Project MYTRI (Mobilizing Youth for Tobacco-Related Initiatives in India) was a large 2-year randomized school-based trial with a goal to reduce and prevent tobacco use among students in 6th and 8th grades in Delhi and Chennai in India (n=32 schools). Baseline analyses in 2004 showed that 6th grade students reported more tobacco use than 8 th grade students, opposite of what is typically observed in developed countries like the US. The present study aims to study differences in tobacco use and psychosocial risk factors between the 6th grade cohort and 8th grade cohort, in a compliant sub-sample of control students that were present at all 3 surveys from 2004-06. Both in 2004 and 2005, 6th grade cohort reported significantly greater prevalence of ever use of all tobacco products (cigarettes, bidis, chewing tobacco, any tobacco). These significant differences in ever use of any tobacco between cohorts were maintained by gender, city and socioeconomic status. The 6th grade cohort also reported significantly greater prevalence of current use of tobacco products (cigarettes, chewing tobacco, any tobacco) in 2004. Similar findings were observed for psychosocial risk factors for tobacco use, where the 6th grade cohort scored higher risk than 8th grade cohort on scales for intentions to smoke or chew tobacco and susceptibility to smoke or chew tobacco in 2004 and 2005, and for knowledge of health effects of tobacco in all three years.^ The evidence of early initiation of tobacco use in our 6th grade cohort in India indicates the need to target prevention programs and other tobacco control measures from a younger age in this setting. With increasing proportions of total deaths and lost DALYs in India being attributable to chronic diseases, addressing tobacco use among younger cohorts is even more critical. Increase in tobacco use among youth is a cause for concern with respect to future burden of chronic disease and tobacco-related mortality in many developing countries. Similarly, epidemiological studies that aim to predict future death and disease burden due to tobacco should address the early age at initiation and increasing prevalence rates among younger populations. ^

Diffusely adherent Escherichia coli (DAEC) as a cause of acute diarrhea

Acute diarrhea is the most common medical problem in the developing countries. Infectious agents are responsible for a majority of cases of acute diarrhea. Knowing the cause of acute diarrhea is important to developing plans for disease prevention, control and therapy. Acute diarrhea is caused by many viruses, bacteria and parasites. ^ Travelers to developing countries of the world commonly develop diarrhea as a result of eating contaminated food or drinking contaminated water. About 30-50% of travelers who travel from industrialized countries like United States to the developing countries are at risk of developing diarrhea. High risk areas for travelers' diarrhea are Mexico, Latin America and Southeast Asia. Public restaurants are the common sites for exposure to this type of food-borne infectious disease in travelers. Food becomes contaminated when they are handled by people with fecal content on their hands. ^ The importance of Diffusely Adherent Escherichia Coli (DAEC) in travelers to these areas has not been well studied. Some of the studies looking at DAEC have shown the organism to be present in children without symptoms. Other studies have shown a relationship between DAEC infection and presence of symptoms. I have selected this topic because the patho-physiological processes in DAEC infection that allow intestinal and extra-intestinal infections to develop are not fully understood. DAEC related acute diarrhea is a relatively new topic of public health significance. There is a limited number of studies regarding the virulence and pathogenic mechanisms of DAEC. The presumed virulence factor of the organism is diffuse attachment to the intestinal lining of the infected host. However more research needs to be done to identify the pathogenic mechanisms and virulence factors associated with DAEC infection for better treatment planning and diarrhea prevention. ^

Frequency, severity and distress of dialysis-related symptoms reported by patients on hemodialysis

Purpose. To determine which symptoms are the most reported, occur most frequently, have the greatest severity, and cause the most bother for hemodialysis (HD) patients and to determine if the symptoms experienced differ between the first (HD 1) and second (HD 2) treatments of the week. ^ Design. An observational, comparative design was used to determine participants' HD symptoms experience on HD 1 and HD 2, and the effect of the symptom experience on Quality of Life (QOL). One hundred subjects were recruited from five dialysis centers. ^ Methods. The adapted Dialysis Frequency, Severity and Symptom Burden Index (DFSSBI) and the Medical Outcomes Study Short Form 36 (MOS SF 36) were administered (N = 99) on HD 1 and the DFSSBI again on HD 2. Data were analyzed for significance among symptoms experience test scores in relation to HD 1 and HD 2, QOL, and gender and age. ^ Results. Of 31 symptoms assessed, respondents reported an average of 9.69 symptoms on HD 1 and 7.51 symptoms on HD 2. Overall, more symptoms were reported, and were more frequent, severe and bothersome on HD 1 when the level of metabolic waste is highest. The most reported symptoms included tiredness, dry skin, difficulty falling asleep, itching, numbness/tingling, difficulty staying asleep, decreased interest in sex, and bone/joint pain. Females scored consistently higher than males in the four symptom dimensions. The respondents reported about the same as the population norm (50) on the physical component summary score of the MOS SF 36 and higher than the norm (65.23) on the mental component summary score. ^ Conclusion. The study findings highlighted the fact that hemodialysis patients experience multiple symptoms that can be frequent, severe, and bothersome. Interventions should be developed and tested to reduce symptom burden and improve QOL. ^

Investigating the pathogenicity of mutations in two ubiquitously expressed housekeeping genes that cause autosomal dominant retinitis pigmentosa

The purpose of this dissertation research was to investigate potential mechanisms through which mutations in two ubiquitously expressed genes, inosine monophosphate dehydrogenase 1 (IMPDH1) and pre-mRNA processing factor 31 (PRPF31), cause autosomal dominant retinitis pigmentosa (adRP) but have no other apparent clinical consequences. Basic properties of the gene and gene product, such as expression and protein levels, were examined. The purpose of our research is to understand the genetic basis of inherited retinopathies such as retinitis pigmentosa (RP). RP is a heterogeneous retinal dystrophy that affects approximately one in 3,700 individuals, making it the most common heritable retinal degenerative disease worldwide. Currently, mutations in 35 genes are known to cause RP and additional loci have been mapped but the underlying gene is not yet known. Often the genes associated with RP are integral to the biological processes underlying vision, making their role in retinal disease easy to explain. However, the mechanisms by which other genes cause RP are not apparent, especially widely-expressed genes. For IMPDH1, this research characterized the enzymatic properties of retinal isoforms. Results show that the retinal isoforms have enzymatic functions similar to the previously known canonical IMPDH1 whether or not an adRP pigmentosa mutation is included in the protein. For PRPF31, this research tested the hypothesis that functional haploinsufficiency is the cause of disease and relates to nonpenetrance in some individuals. Studies in patients with known mutations show that haploinsufficiency is the likely cause of disease, however, we did not confirm that non-penetrant individuals are protected from disease via increased expression of the wild type allele. Information gleaned from these functional studies, and the testing methods developed in tandem, will contribute to future research on disease mechanism related to adRP. ^

Nursing-related medication errors: A review of factors that facilitate and hinder error reporting, and recommendations for improvement

Medication errors, one of the most frequent types of medical errors, are a common cause of patient harm in hospital systems today. Nurses at the bedside are in a position to encounter many of these errors since they are there at the start of the process (ordering/prescribing) and the end of the process (administration). One of the recommendations from the IOM (Institute of Medicine) report, "To Err is Human," was for organizations to identify and learn from medical errors through event reporting systems. While many organizations have reporting systems in place, research studies report a significant amount of underreporting by nurses. A systematic review of the literature was performed to identify contributing factors related to the reporting and not reporting of medication errors by nurses at the bedside.^ Articles included in the literature review were primary or secondary studies, dated January 1, 2000 – July 2009, related to nursing medication error reporting. All 634 articles were reviewed with an algorithm developed to standardize the review process and help filter out those that did not meet the study criteria. In addition, 142 article bibliographies were reviewed to find additional studies that were not found in the original literature search.^ After reviewing the 634 articles and the additional 108 articles discovered in the bibliography review, 41 articles met the study criteria and were used in the systematic literature review results.^ Fear of punitive reactions to medication errors was a frequent barrier to error reporting. Nurses fear reactions from their leadership, peers, patients and their families, nursing boards, and the media. Anonymous reporting systems and departments/organizations with a strong safety culture in place helped to encourage the reporting of medication errors by nursing staff.^ Many of the studies included in this literature review do not allow results that can be generalized. The majority of them took place in single institutions/organizations with limited sample sizes. Stronger studies with larger sample sizes need to be performed, utilizing data collection methods that have been validated, to determine stronger correlations between safety cultures and nurse error reporting.^

A critical review: Why isn't "cold pasteurization" being used widespread as a method to prevent food-related illnesses as a result of the consumption of ready-to-eat, fresh fruits, and vegetables

The Centers for Disease Control estimates that foodborne diseases cause approximately 76 million illnesses, 325,000 hospitalizations, and 5,000 deaths in the United States each year. The American public is becoming more health conscious and there has been an increase in the dietary intake of fresh fruits and vegetables. Affluence and demand for convenience has allowed consumers to opt for pre-processed packaged fresh fruits and vegetables. These pre-processed foods are considered Ready-to-Eat. They have many of the advantages of fresh produce without the inconvenience of processing at home. After seeing a decline in food-related illnesses between 1996 and 2004, due to an improvement in meat and poultry safety, tainted produce has tilted the numbers back. This has resulted in none of the Healthy People 2010 targets for food-related illness reduction being reached. Irradiation has been shown to be effective in eliminating many of the foodborne pathogens. The application of irradiation as a food safety treatment has been widely endorsed by many of the major associations involved with food safety and public health. Despite these endorsements there has been very little use of this technology to date for reducing the disease burden associated with the consumption of these products. A review of the available literature since the passage of the 1996 Food Quality Protection Act was conducted on the barriers to implementing irradiation as a food safety process for fresh fruits and vegetables. The impediments to adopting widespread utilization of irradiation food processing as a food safety measure involve a complex array of legislative, regulatory, industry, and consumer issues. The FDA’s approval process limits the expansion of the list of foods approved for the application of irradiation as a food safety process. There is also a lack of capacity within the industry to meet the needs of a geographically dispersed industry.^

Model simulation output data (CCSM3) related to uplift of African topography and the intensification of upwelling in the Benguela region

The Benguela Current, located off the west coast of southern Africa, is tied to a highly productive upwelling system**1. Over the past 12 million years, the current has cooled, and upwelling has intensified**2, 3, 4. These changes have been variously linked to atmospheric and oceanic changes associated with the glaciation of Antarctica and global cooling**5, the closure of the Central American Seaway**1, 6 or the further restriction of the Indonesian Seaway**3. The upwelling intensification also occurred during a period of substantial uplift of the African continent**7, 8. Here we use a coupled ocean-atmosphere general circulation model to test the effect of African uplift on Benguela upwelling. In our simulations, uplift in the East African Rift system and in southern and southwestern Africa induces an intensification of coastal low-level winds, which leads to increased oceanic upwelling of cool subsurface waters. We compare the effect of African uplift with the simulated impact of the Central American Seaway closure9, Indonesian Throughflow restriction10 and Antarctic glaciation**11, and find that African uplift has at least an equally strong influence as each of the three other factors. We therefore conclude that African uplift was an important factor in driving the cooling and strengthening of the Benguela Current and coastal upwelling during the late Miocene and Pliocene epochs.

Experiment on wound activated production of Prostaglandin E2 and related toxic compounds in populations of Gracilaria vermiculophylla

The capacity of the East Asian seaweed Gracilaria vermiculophylla ("Ogonori") for production of prostaglandin E2 from arachidonic acid occasionally causes food poisoning after ingestion. During the last two decades the alga has been introduced to Europe and North America. Non-native populations have been shown to be generally less palatable to marine herbivores than native populations. We hypothesized that the difference in palatability among populations could be due to differences in the algal content of prostaglandins. We therefore compared the capacity for wound-activated production of prostaglandins and other eicosatetraenoid oxylipins among five native populations in East Asia and seven non-native populations in Europe and NW Mexico, using a targeted metabolomics approach. In two independent experiments non-native populations exhibited a significant tendency to produce more eicosatetraenoids than native populations after acclimation to identical conditions and subsequent artificial wounding. Fourteen out of 15 eicosatetraenoids that were detected in experiment I and all 19 eicosatetraenoids that were detected in experiment II reached higher mean concentrations in non-native than in native specimens. The datasets generated in both experiments are contained in http://doi.pangaea.de/10.1594/PANGAEA.855008. Wounding of non-native specimens resulted on average in 390 % more 15-keto-PGE2, in 90 % more PGE2, in 37 % more PGA2 and in 96 % more 7,8-di-hydroxy eicosatetraenoic acid than wounding of native specimens. The dataset underlying this statement is contained in http://doi.pangaea.de/10.1594/PANGAEA.854847. Not only PGE2, but also PGA2 and dihydroxylated eicosatetraenoic acid are known to deter various biological enemies of G. vermiculophylla that cause tissue or cell wounding, and in the present study the latter two compounds also repelled the mesograzer Littorina brevicula. The dataset underlying this statement is contained in http://doi.pangaea.de/10.1594/PANGAEA.854922. Non-native populations of G. vermiculophylla are thus more defended against herbivory than native populations. This increased capacity for activated chemical defense may have contributed to their invasion success and at the same time it poses an elevated risk for human food safety.

Who Develops Innovations in Medicine for the Poor? Trends in Patent Applications Related to Medicines for HIV/AIDS, Tuberculosis, Malaria and Neglected Diseases

Who invents medicines for the poor of the world? This question becomes very important where the WTO allows low income countries to be unbound by the TRIPS agreement. This agreement concerns medicines for infectious diseases such as HIV/AIDS, tuberculosis and malaria. These diseases cause serious damage to low income countries. Under these circumstances, some scholars wonder if anyone will continue innovative activities related to treating these diseases. This paper sought to answer this question by collecting and analyzing patent data of medicines and vaccines for diseases using the database of the Japan Patent Office. Results indicate that private firms have led in innovation not only for global diseases such as HIV/AIDS but also diseases such as malaria that are spreading exclusively in low income countries. Innovation for the three infectious diseases is diverse among firms, and frequent patent applications by high-performing pharmaceutical firms appear prominent even after R&D expenditure, economies of scale, and economies of scope are taken into account.

As Estratégias de Marketing e de Comunicação utilizadas na Educação a Distância

Este trabalho visa conhecer e analisar as ferramentas de marketing e de comunicação utilizadas pela Universidade Metodista de São Paulo, pela Universidade Anhembi Morumbi e pela Universidade de São Paulo em seus cursos de Educação a Distância, bem como nas disciplinas semipresenciais oferecidas pelas referidas instituições, através de pesquisas nos sites e entrevistas com os responsáveis pela elaboração da EaD nas instituições. Tenciona ainda, comparar as estratégias criadas por essas instituições no desenvolvimento de seus cursos e disciplinas, além de conhecer e analisar a comunicação elaborada por elas, como forma de divulgar e persuadir seus públicos-alvo. Objetiva também buscar o conhecimento e a percepção que seus alunos possuem desses cursos e disciplinas e da Educação a Distância como um todo, através de entrevistas individuais e utilizando um questionário estruturado.(AU)

As Estratégias de Marketing e de Comunicação utilizadas na Educação a Distância

Este trabalho visa conhecer e analisar as ferramentas de marketing e de comunicação utilizadas pela Universidade Metodista de São Paulo, pela Universidade Anhembi Morumbi e pela Universidade de São Paulo em seus cursos de Educação a Distância, bem como nas disciplinas semipresenciais oferecidas pelas referidas instituições, através de pesquisas nos sites e entrevistas com os responsáveis pela elaboração da EaD nas instituições. Tenciona ainda, comparar as estratégias criadas por essas instituições no desenvolvimento de seus cursos e disciplinas, além de conhecer e analisar a comunicação elaborada por elas, como forma de divulgar e persuadir seus públicos-alvo. Objetiva também buscar o conhecimento e a percepção que seus alunos possuem desses cursos e disciplinas e da Educação a Distância como um todo, através de entrevistas individuais e utilizando um questionário estruturado.(AU)

RELIGIÃO E MARKETING PESSOAL: UMA ANÁLISE DA IMAGEM PESSOAL DOS BISPOS, PASTORES, OBREIROS E OBREIRAS DA IGREJA UNIVERSAL DO REINO DE DEUS

Este trabalho tem por objetivo analisar a forma de construção da imagem dos bispos, pastores, obreiros e obreiras da Igreja Universal do Reino de Deus (IURD), por meio da ferramenta de marketing pessoal (MP). A utilização do MP por tais agentes religiosos é uma maneira de melhorar a interação simbólica entre líderes e fiéis e atrair o público para os templos. A IURD foi escolhida para esta análise por usar de vários procedimentos que estão relacionados com as técnicas de MP, no sentido de sofisticar a aparência visual de sua liderança, a fim de representar um discurso de prosperidade disseminado pela instituição. Cremos que é dessa forma que a IURD atrai o público por meio da imagem criada dos líderes, mediante uma aparência visual sofisticada. Na pesquisa dessa Igreja, encontramos que a ferramenta de MP usada pelos seus membros hierárquicos contribui para o crescimento e a consolidação desse empreendimento no mercado religioso. A construção da imagem que estamos tratando é planejada a partir da matriz imagética do líder principal da Igreja Universal, Edir Bezerra Macedo. Por meio da imagem central do bispo Macedo é que a liderança é marcada ou estigmatizada com um perfil estético respaldado por uma noção de sucesso. Utilizamos a pesquisa bibliográfica e observação participante como método de pesquisa e ainda, pesquisamos o jornal Folha Universal e averiguamos alguns programas televisivos exibidos na TV Record, analisando o marketing pessoal da liderança em questão. Assim, verificamos que as interfaces de presentação da boa imagem produzida por meio de técnicas corporais, roupas e acessórios, favorece a representação desses líderes nos seus principais canais de comunicação, templos e televisão.(AU)

RELIGIÃO E MARKETING PESSOAL: UMA ANÁLISE DA IMAGEM PESSOAL DOS BISPOS, PASTORES, OBREIROS E OBREIRAS DA IGREJA UNIVERSAL DO REINO DE DEUS

Este trabalho tem por objetivo analisar a forma de construção da imagem dos bispos, pastores, obreiros e obreiras da Igreja Universal do Reino de Deus (IURD), por meio da ferramenta de marketing pessoal (MP). A utilização do MP por tais agentes religiosos é uma maneira de melhorar a interação simbólica entre líderes e fiéis e atrair o público para os templos. A IURD foi escolhida para esta análise por usar de vários procedimentos que estão relacionados com as técnicas de MP, no sentido de sofisticar a aparência visual de sua liderança, a fim de representar um discurso de prosperidade disseminado pela instituição. Cremos que é dessa forma que a IURD atrai o público por meio da imagem criada dos líderes, mediante uma aparência visual sofisticada. Na pesquisa dessa Igreja, encontramos que a ferramenta de MP usada pelos seus membros hierárquicos contribui para o crescimento e a consolidação desse empreendimento no mercado religioso. A construção da imagem que estamos tratando é planejada a partir da matriz imagética do líder principal da Igreja Universal, Edir Bezerra Macedo. Por meio da imagem central do bispo Macedo é que a liderança é marcada ou estigmatizada com um perfil estético respaldado por uma noção de sucesso. Utilizamos a pesquisa bibliográfica e observação participante como método de pesquisa e ainda, pesquisamos o jornal Folha Universal e averiguamos alguns programas televisivos exibidos na TV Record, analisando o marketing pessoal da liderança em questão. Assim, verificamos que as interfaces de presentação da boa imagem produzida por meio de técnicas corporais, roupas e acessórios, favorece a representação desses líderes nos seus principais canais de comunicação, templos e televisão.(AU)

Analysis of three structurally related antiviral compounds in complex with human rhinovirus 16

Rhinoviruses are a frequent cause of the common cold. A series of antirhinoviral compounds have been developed that bind into a hydrophobic pocket in the viral capsid, stabilizing the capsid and interfering with cell attachment. The structures of a variety of such compounds, complexed with rhinovirus serotypes 14, 16, 1A, and 3, previously have been examined. Three chemically similar compounds, closely related to a drug that is undergoing phase III clinical trials, were chosen to determine the structural impact of the heteroatoms in one of the three rings. The compounds were found to have binding modes that depend on their electronic distribution. In the compound with the lowest efficacy, the terminal ring is displaced by 1 Å and rotated by 180° relative to the structure of the other two. The greater polarity of the terminal ring in one of the three compounds leads to a small displacement of its position relative to the other compounds in the hydrophobic end of the antiviral compound binding pocket to a site where it makes fewer interactions. Its lower efficacy is likely to be the result of the reduced number of interactions. A region of conserved residues has been identified near the entrance to the binding pocket where there is a corresponding conservation of the mode of binding of these compounds to different serotypes. Thus, variations in residues lining the more hydrophobic end of the pocket are primarily responsible for the differences in drug efficacies.