Losartan Decreases p42/44 MAPK Signaling and Preserves LZ+ MYPT1 Expression

Heart failure is associated with impairment in nitric oxide (NO) mediated vasodilatation, which has been demonstrated to result from a reduction in the relative expression of the leucine zipper positive (LZ+) isoform of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase. Further, captopril preserves normal LZ+ MYPT1 expression, the sensitivity to cGMP-mediated vasodilatation and modulates the expression of genes in the p42/44 MAPK and p38 MAPK signaling cascades. This study tests whether angiotensin receptor blockade (ARB) with losartan decreases p42/44 MAPK or p38 MAPK signaling and preserves LZ+ MYPT1 expression in a rat infarct model of heart failure. In aortic smooth muscle, p42/44 MAPK activation increases and LZ+ MYPT1 expression falls after LAD ligation. Losartan treatment decreases the activation of p42/44 MAPK to the uninfarcted control level and preserves normal LZ+ MYPT1 expression. The expression and activation of p38 MAPK, however, is low and does not change following LAD ligation or with losartan therapy. These data suggest that either reducing or blocking the effects of circulating angiotensin II, both decreases the activation of the p42/44 MAPK signaling cascade and preserves LZ+ MYPT1 expression. Thus, the ability of ACE-inhibitors and ARBs to modulate the vascular phenotype, to preserve normal flow mediated vasodilatation may explain the beneficial effects of these drugs compared to other forms of afterload reduction in the treatment of heart failure

Towards Electrosynthesis in Shewanella: Energetics of Reversing the Mtr Pathway for Reductive Metabolism

Bioelectrochemical systems rely on microorganisms to link complex oxidation/reduction reactions to electrodes. For example, in Shewanella oneidensis strain MR-1, an electron transfer conduit consisting of cytochromes and structural proteins, known as the Mtr respiratory pathway, catalyzes electron flow from cytoplasmic oxidative reactions to electrodes. Reversing this electron flow to drive microbial reductive metabolism offers a possible route for electrosynthesis of high value fuels and chemicals. We examined electron flow from electrodes into Shewanella to determine the feasibility of this process, the molecular components of reductive electron flow, and what driving forces were required. Addition of fumarate to a film of S. oneidensis adhering to a graphite electrode poised at −0.36 V versus standard hydrogen electrode (SHE) immediately led to electron uptake, while a mutant lacking the periplasmic fumarate reductase FccA was unable to utilize electrodes for fumarate reduction. Deletion of the gene encoding the outer membrane cytochrome-anchoring protein MtrB eliminated 88% of fumarate reduction. A mutant lacking the periplasmic cytochrome MtrA demonstrated more severe defects. Surprisingly, disruption of menC, which prevents menaquinone biosynthesis, eliminated 85% of electron flux. Deletion of the gene encoding the quinone-linked cytochrome CymA had a similar negative effect, which showed that electrons primarily flowed from outer membrane cytochromes into the quinone pool, and back to periplasmic FccA. Soluble redox mediators only partially restored electron transfer in mutants, suggesting that soluble shuttles could not replace periplasmic protein-protein interactions. This work demonstrates that the Mtr pathway can power reductive reactions, shows this conduit is functionally reversible, and provides new evidence for distinct CymA:MtrA and CymA:FccA respiratory units

Predicting intention to treat HIV-infected patients among Tanzanian and Sudanese medical and dental students using the theory of planned behaviour - a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic poses significant challenges to the low income countries in sub Saharan Africa (SSA), affecting the attrition rate among health care workers, their level of motivation, and absenteeism from work. Little is known about how to deal with deterioration of human resources in the health care systems. This study aimed to predict the intention to provide surgical treatment to HIV infected patients among medical- and dental students in Tanzania and Sudan using an extended version of the Theory of Planned Behaviour (TPB).</p> <p>Methods</p> <p>Four hundred and seventy five medical- and dental students at the University of Dar es Salaam (mean age, 25 yr) and 642 dental students attending 6 public and private dental faculties in Khartoum (mean age 21.7 yr) completed self-administered TPB questionnaires in 2005 and 2007, respectively.</p> <p>Results</p> <p>Both Tanzanian and Sudanese students demonstrated strong intentions to provide care for people with HIV and AIDS. Stepwise linear regression revealed that the TPB accounted for 51% (43% in Tanzania and Sudan) of the variance in intention across study sites. After having controlled for country and past behaviour, the TPB in terms of attitudes, subjective norms and perceived behavioural control accounted for 34% and moral norms for an additional 2,3% of the explainable variance in intention. Across both study sites, attitudes were the strongest predictor of intention followed in descending order by subjective norms, moral norms and perceived behavioural control.</p> <p>Conclusion</p> <p>The TPB is applicable to students' care delivery intentions in the context of HIV and AIDS across the two SSA countries investigated. It is suggested that attitudes, subjective norms, moral norms and perceived behavioural control are key factors in students' willingness to treat AIDS and HIV infected patients and should be targets of interventions aimed at improving the quality of health care delivery in this context.</p

The long-term consequences of retrieval demands during working memory

Although it is well known that distraction impairs immediate retrieval of items maintained in working memory (WM; e.g., during complex span tasks), some evidence suggests that these items are more likely to be recalled from episodic memory (EM) compared with items that were studied without any distraction (e.g., during simple span tasks). One account for this delayed advantage of complex span over simple span, or the McCabe effect (McCabe, Journal of Memory and Language, 58[2], 480–494, 2008), is that complex span affords covert retrieval opportunities that facilitate later retrieval from EM by cumulatively reactivating each successively presented item after distraction. This explanation focuses on the processing that occurs during presentation and maintenance of the items, but no work to date has explored whether the differential demands of immediate retrieval between simple and complex span may explain the effect. Accordingly, these experiments examined the impact of immediate retrieval demands on the McCabe effect by comparing typical immediate serial-recall instructions (i.e., recalling the words in their exact order of presentation) to immediate free-recall (Experiments 1–2) and no-recall (Experiments 2 and 3) instructions. The results suggested that the nature of retrieval may constrain the McCabe effect in some situations (Experiments 1–2), but its demands do not drive the McCabe effect given that it was observed in both serial-recall and no-recall conditions (Experiment 3). Instead, activities such as covert retrieval during the processing phase may underlie the McCabe effect, thus further evidencing the importance of processing in WM for the long-term retention of information

Perfil nosológico de centro de referência em dermatologia no estado do Amazonas - Brasil Nosological profile in a dermatology referral center in the state of Amazonas -Brazil

FUNDAMENTOS: As doenças de pele estão associadas a alta morbidade, baixa mortalidade e baixa proporção de hospitalização. Entretanto, podem causar considerável interferência no bem-estar físico e emocional do indivíduo. Várias delas atingem grandes contingentes populacionais, havendo necessidade de intervenções específicas para seu controle. OBJETIVO: Descrever a frequência das dermatoses diagnosticadas em serviço de dermatologia na cidade de Manaus, capital do estado do Amazonas. MÉTODOS: Coletaram-se dados registrados sobre sexo, idade, procedência e diagnósticos referentes à primeira consulta dos pacientes atendidos entre janeiro de 2000 e dezembro de 2007. RESULTADOS: Das 56.024 consultas registradas, obtiveram-se 56.720 diagnósticos dermatológicos, sendo mais comuns as doenças sexualmente transmissíveis (25,12%), as dermatoses alérgicas (14,03%), as dermatoses não especificadas (13,01%), a hanseníase (6,34%) e acne, seborreia e afins (5,05%). A frequência foi semelhante para ambos os sexos, a faixa etária de 20-29 anos foi predominante e Manaus foi a procedência mais referida. CONCLUSÕES: O padrão das doenças cutâneas identificadas neste estudo pode servir como linha de base para que gestores do sistema de saúde da região desenvolvam estratégias de prevenção e controle das dermatoses mais comuns, com ênfase nas doenças sexualmente transmissíveis, doenças cutâneas alérgicas, hanseníase e acne<br>BACKGROUNDS: Fundaments: Skin diseases are associated wih high morbidity, low mortality and low rate of hospitalization. However, they can cause considerable interference in physical and emotional well-being of the individual. Several of them reach large population, requiring specific interventions for their control. OBJECTIVE: To describe the frequency of skin disease diagnosed in the dermatology service in Manaus, capital of Amazonas State. METHODS: We collected data on registered sex, age, origin and diagnostics for the first consultation of patients attended between January 2000 and December 2007. RESULTS: Of the 56.024 recorded visits, we obtained 56.720 cases of dermatological diagnoses, being the most common sexually transmitted diseases (25,12%), allergic skin disesases (14,03%), unspecified dermatoses (13,01%), leprosy (6,34%) and acne, seborrhea and related diseases (5,05%). The frequency was similar for both sexes, aged 20-29 years predominated and Manaus the origin most reported. CONCLUSIONS: The pattern of skin diseases identified in this study may serve as a baseline to managers of health system in the region develop strategies for prevention and control of dermatoses, with emphasis on sexually transmitted diseases, allergic skin diseases, leprosy and acn