Virulence related sequences: insights provided by comparative genomics of Streptococcus uberis of differing virulence

Background: Streptococcus uberis, a Gram-positive, catalase-negative member of the family Streptococcaceae is an important environmental pathogen responsible for a significant proportion of subclinical and clinical bovine intramammary infections. Currently, the genome of only a single reference strain (0140J) has been described. Here we present a comparative analysis of complete draft genome sequences of an additional twelve S. uberis strains. Results: Pan and core genome analysis revealed the core genome common to all strains to be 1,550 genes in 1,509 orthologous clusters, complemented by 115-246 accessory genes present in one or more S. uberis strains but absent in the reference strain 0140J. Most of the previously predicted virulent genes were present in the core genome of all 13 strains but gene gain/loss was observed between the isolates in CDS associated with clustered regularly interspaced short palindromic repeats (CRISPRs), prophage and bacteriocin production. Experimental challenge experiments confirmed strain EF20 as non-virulent; only able to infect in a transient manner that did not result in clinical mastitis. Comparison of the genome sequence of EF20 with the validated virulent strain 0140J identified genes associated with virulence, however these did not relate clearly with clinical/non-clinical status of infection. Conclusion: The gain/loss of mobile genetic elements such as CRISPRs and prophage are a potential driving force for evolutionary change. This first “whole-genome” comparison of strains isolated from clinical vs non-clinical intramammary infections including the type virulent vs non-virulent strains did not identify simple gene gain/loss rules that readily explain, or be confidently associated with, differences in virulence. This suggests that a more complex dynamic determines infection potential and clinical outcome not simply gene content

Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis

Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses. TLR4 is the most studied of the TLRs, and its primary exogenous ligand is lipopolysaccharide, a component of Gram-negative bacterial walls. In the absence of exogenous microbes, endogenous ligands including damage-associated molecular pattern molecules from damaged matrix and injured cells can also activate TLR4 signaling. In humans, single nucleotide polymorphisms of the TLR4 gene have an effect on its signal transduction and on associated risks of specific diseases, including cirrhosis. In liver, TLR4 is expressed by all parenchymal and non-parenchymal cell types, and contributes to tissue damage caused by a variety of etiologies. Intact TLR4 signaling was identified in hepatic stellate cells (HSCs), the major fibrogenic cell type in injured liver, and mediates key responses including an inflammatory phenotype, fibrogenesis and anti-apoptotic properties. Further clarification of the function and endogenous ligands of TLR4 signaling in HSCs and other liver cells could uncover novel mechanisms of fibrogenesis and facilitate the development of therapeutic strategies

Hemorragia maciça do intestino grosso: o que está ao nosso alcance? Massive large bowel bleeding: what is within our reach?

A forma de avaliar e lidar com a hemorragia aguda digestiva baixa tem sido modificado com os recentes desenvolvimentos de novas técnicas e aparelhos. O nosso objetivo, por esse manuscrito, é demonstrar com simplicidade uma forma de condução dos pacientes com hemorragia digestiva baixa aguda, sobretudo para os sangramentos que parecem mais graves, principalmente quando nos faltam os recursos das avançadas tecnologias atuais. Doenças localizadas no intestino grosso respondem por ¼ dos casos de hemorragias digestivas que são motivos para admissão hospitalar e têm como principais agentes etiológicos os divertículos, na moléstia diverticular, e as alterações vasculares, nas angiodisplasias. Na grande maioria das vezes o sangramento que pode parecer abundante cessa espontaneamente. Os distúrbios circulatórios graves não são comuns e os sinais mais frequentes são a queda do valor da hemoglobina observada na metade dos pacientes, e algumas alterações hemodinâmicas como a variação pressórica postural que pode ser vista em até 30% dos casos; a síncope em 10% e alguma forma de colapso circulatório, em 9%. Contudo, a faixa etária em que ocorre, as condições da senilidade, as doenças eventualmente associadas e a falta de recursos materiais e humanos para lidar com esse tipo de problema são os motivos que mais causam preocupação. A abordagem clínica simples com uma história bem elaborada; o exame físico com atenção e objetividade, a inclusão do exame proctológico, a obrigatória disponibilidade de aparelho para a coloscopia e os conhecimentos básicos sobre o evento formam o conjunto necessário e, na maioria das vezes, suficiente para o correto desempenho profissional na elaboração dos cuidados que devem ser dados a esses pacientes.<br>The evaluation and management of the acute lower digestive hemorrhage has been modified with the recent development of new techniques and devices. The aim of this manuscript was to demonstrate with simplicity how to treat the patients with acute lower intestinal hemorrhage. Diseases of the large bowel account for the ¼ of the cases of digestive hemorrhages on the hospital admission and have as main etiological agents the diverticula, in the diverticular disease, and small vascular malformation, in the angiodysplasias. Sometime, it can be seen as a life-threatening condition, however, most of the times, the hemorrhage stops spontaneously. The serious circulatory disturbances are not common; the most frequent signs are the decrease in hemoglobin occurring on about one half of patients and some form of circulatory disturbance as orthostatic changes in 30%; as syncope in 10% and as cardiovascular collapse in 9%. However, the age group, the conditions of the senility, the eventually associated diseases and the lack of material and human resources to handle with that kind of problem are the reasons for concern. The simple clinical approach with a well elaborated history; the physical examination released with attention and objectivity, the inclusion of the proctologic exam, the obligatory readiness for an endoscope for colonoscopy, the basic knowledge on the event are necessary and, in most of the times, enough for the good professional acting in the elaboration of the cares that it should be given to those patient ones

The association between spirituality and depression in parents caring for children with developmental disabilities: social support and/or last resort

Associations between spirituality and depression were examined in parents of children with developmental disabilities using both quantitative and qualitative methodology. Spirituality was positively associated with depression, whereas social support was negatively related; parents with higher spiritual beliefs and lower levels of support had higher depression scores. Themes emerging from interviews were spiritual/religious coping as a way of dealing with difficulty, as a last resort, and as a form of release from their situation. Associations between spirituality and depression in these parents are more complex than previously thought