The albumin-bilirubin score predicting the mortality of patients with decompensated cirrhosis.

info:eu-repo/semantics/publishedVersio

Development of a predictive model for phage-bacteria interaction

The prevalence and impact of bacteriophages in the ecology of bacterial communities coupled with their ability to control pathogens turns essential to understand and predict the existing dynamics between phage and bacteria populations. The success of phage therapy is dependent on the knowledge of the phage replication kinetic properties in the presence of the host as well as on the prediction, controlling and optimization of phage production for future application. To achieve this knowledge it is important to develop mathematical models able to explain and simulate the population dynamics of phage and bacteria. We have developed a mathematical model using delay-differential equations to predict the interaction between a broad-host-range Salmonella phage and its pathogenic host. The model takes into consideration the main biological parameters that rule phagebacteria interactions likewise the latent period. burst size, bacterial growth rate, substrate uptake rate among others. The experimental validation of the model was performed in a bioreactor and it was found that the bacterial growth rate is critical to understand and predict the phage growth and bacterial control. By modelling the adsorption rate as a function of the bacterial growth rate it was possible to accurately predict the behaviour of the phage-bacteria population. The model generates data with a good agreement with the experimental observations and explains how a lytic phage and its host bacteria are able to coexist. Consequently, the model can be used to explain the structure of ecological communities of phages and bacteria and also to optimize phage production and guide the experimental studies of population dynamics by identifying and evaluating the relative contribution of phage and bacteria in the course and outcome of an infection

Genome characterization of two valuable therapeutic bacteriophages against Salmonella and Campylobacter

Book of abstracts of the Meeting of the Institute for Biotechnology and Bioengineering, 2, Braga, Portugal, 2010Salmonella and Campylobacter are recognized worldwide as the major foodborne pathogens responsible for human gastrointestinal diseases. The increased resistance of bacteria to antibiotics has encouraged the development of alternatives to control bacterial pathogens. Bacteriophages (phages), as natural predators of bacteria, are considered an appealing option. We report herein the isolation and genome characterisation of two Myoviridae broad lytic spectra Campylobacter (vB_CcoM-IBB35) and Salmonella phages (PVP-SE1) with high potential for therapy. The majority of genes of vB_CcoM-IBB35 are unique although homology exists with members of the Teequatrovirinae. Unique genes involved in pathogenesis, carbohydrate and amino acid metabolism were also observed along with several incidences of gene duplications, split genes with intein and introns and “insertion-like sequences”. From the 244 genes found in PVP-SE1, approximately 46% encode unique proteins and only 22.1% exhibited homology with known proteins. The genome sequence presents high homology (145 gene encoding proteins) with the E.coli bacteriophage rV5, both unrelated to any other known phage, which might suggest that they belong to a new phage genetic group. As conclusion, one can argue that the genomic characterization of both phages did not reveal any factor which could preclude its therapeutic use

Estamos a ser eficazes na erradicação de Helicobacter Pylori?

Foram incluídos 328 doentes. • 75.9% (n=249) receberam esquema quadruplo com bismuto(QB) ou quádruplo concomitante (QC) como terapêutica de primeira linha com taxa de erradicação >80% (gráfico 1), semelhante à descrita na literatura. • 20,1% (n=66) receberam terapêutica tripla com claritromicina com uma taxa de erradicação de 51,5%, significativamente inferior à de QC e QB. • Da terapêutica de resgate (n=77) a QB e o esquema triplo com levofloxacina foram as mais prescritas, com taxas de erradicação de 75,6% e 57,1%, respetivamente. • Dos fatores de risco para falência (Tabela 2): identificou-se a duração prescrita da QC com falência significativamente superior sem inferior a 14 dias); doentes sob QC ou QB a subpopulação natural de país Africano teve taxa de erradicação inferior à da subpopulação Portuguesa. As recomendações atuais do consenso de Maastricht VI/Florence estão adequadas à nossa população, no entanto, não se evidencia totalmente a sua implementação.info:eu-repo/semantics/publishedVersio

Recurrent Gastrointestinal Bleeding from Dieulafoy’s Lesions in a Patient with Type 1 von Willebrand Disease: A Rare Association

Von Willebrand disease (vWD) is the most prevalent hereditary bleeding disorder, affecting 0.6–1.3% of the population. While gastrointestinal bleeding from angiodysplasia is a well-known complication of vWD, the same is not true for Dieulafoy’s lesions (DLs). We report the case of a 21-year-old black male with type 1 vWD and 2 previous hospital admissions for severe anemia with no visible blood loss. In both episodes, DLs were identified and treated endoscopically, one in the stomach and another in the duodenum. The patient presented to the emergency department in September 2016 with dizziness, fatigue, and again no visible blood loss. He was hemodynamically stable, and laboratory workup showed a hemoglobin level of 3.4 g/dL. After transfusion of packed red blood cells, intravenous iron, and von Willebrand factor/factor VIII concentrate infusions, the patient underwent upper endoscopy and colonoscopy, which were normal. Small-bowel capsule endoscopy showed dark blood and a fresh clot in the proximal jejunum. At this site, push enteroscopy identified a pulsatile vessel with an overlying minimal mucosal defect, consistent with a DL, type 2b of the Yano-Yamamoto classification, which was successfully treated with adrenaline and 2 hemoclips. The patient remains stable after 18 months of follow-up, with a hemoglobin level of 13.2 g/dL. This is a case of recurrent severe occult gastrointestinal bleeding from multiple DL in a young patient with vWD who is otherwise healthy. Three other cases of DL bleeding in the setting of vWD have been reported in the literature, suggesting a possible association between these 2 entities

Safety issues concerning phage therapy for veterinary applications

Phages have been proposed as natural antimicrobial agents to fight bacterial infections in animals. This is supported by several scientific evidences of the efficacy of phage therapy for veterinary applications. However, there are important safety issues that should be taken into consideration when developing a phage product for veterinary applications. For example it is of utmost importance to guarantee that phages are non‐temperate and do not encode bacterial toxins. The phage administration strategy and timing should also be adequate in order to reduce the development of phage‐resistant mutants. The present work describes the main strategies used to ensure a safe phage product for veterinary application, based on the results obtained on the scope of the European Project Phagevet‐P (Veterinary Phage Therapies as Alternatives to Antibiotics in Poultry Production FP6‐2003‐Food‐2‐A:007224)

Effects of 3,4-Methylenedioxymethamphetamine Administration on Retinal Physiology in the Rat

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known to produce euphoric states, but may also cause adverse consequences in humans, such as hyperthermia and neurocognitive deficits. Although MDMA consumption has been associated with visual problems, the effects of this recreational drug in retinal physiology have not been addressed hitherto. In this work, we evaluated the effect of a single MDMA administration in the rat electroretinogram (ERG). Wistar rats were administered MDMA (15 mg/kg) or saline and ERGs were recorded before (Baseline ERG), and 3 h, 24 h, and 7 days after treatment. A high temperature (HT) saline-treated control group was also included. Overall, significantly augmented and shorter latency ERG responses were found in MDMA and HT groups 3 h after treatment when compared to Baseline. Twenty-four hours after treatment some of the alterations found at 3 h, mainly characterized by shorter latency, tended to return to Baseline values. However, MDMA-treated animals still presented increased scotopic a-wave and b-wave amplitudes compared to Baseline ERGs, which were independent of temperature elevation though the latter might underlie the acute ERG alterations observed 3 h after MDMA administration. Seven days after MDMA administration recovery from these effects had occurred. The effects seem to stem from specific changes observed at the a-wave level, which indicates that MDMA affects subacutely (at 24 h) retinal physiology at the outer retinal (photoreceptor/bipolar) layers. In conclusion, we have found direct evidence that MDMA causes subacute enhancement of the outer retinal responses (most prominent in the a-wave), though ERG alterations resume within one week. These changes in photoreceptor/bipolar cell physiology may have implications for the understanding of the subacute visual manifestations induced by MDMA in humans

Histological inflammation in the endoscopically uninflamed mucosa is associated with worse outcomes in limited ulcerative colitis

Background: The Montreal classification categorizes patients with ulcerative colitis (UC) based on their macroscopic disease extent. Independent of endoscopic extent, biopsies through all colonic segments should be retrieved during index colonoscopy. However, the prognostic value of histological inflammation at diagnosis in the inflamed and uninflamed regions of the colon has never been assessed.Methods: This was a multicenter retrospective cohort study of newly diagnosed patients with treatment-naïve proctitis and left-sided UC. Biopsies from at least 2 colonic segments (endoscopically inflamed and uninflamed mucosa) were retrieved and reviewed by 2 pathologists. Histological features in the endoscopically inflamed and uninflamed mucosa were scored using the Nancy score. The primary outcomes were disease complications (proximal disease extension, need for hospitalization or colectomy) and higher therapeutic requirements (need for steroids or for therapy escalation).Results: Overall, 93 treatment-naïve patients were included, with a median follow-up of 44 months (range, 2-329). The prevalence of any histological inflammation above the endoscopic margin was 71%. Proximal disease extension was more frequent in patients with histological inflammation in the endoscopically uninflamed mucosa at diagnosis (21.5% vs 3.4%, P = 0.04). Histological involvement above the endoscopic margin was the only predictor associated with an earlier need for therapy escalation (adjusted hazard ratio, 3.69; 95% confidence interval, 1.05- 13.0); P = 0.04) and disease complications (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10-20.9; P = 0.04).Conclusions: The presence of histological inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC.peer-reviewe