From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

Supporting mental health, wellbeing and study skills in Higher Education:an online intervention system

Abstract Background Dealing with psychological and study skill difficulties can present a challenge for both Higher Education (HE) students, who suffer from them, but also for HE Institutions and their support services. Alternative means of support, such as online interventions, have been identified as cost-effective and efficient ways to provide inclusive support to HE students, removing many of the barriers to help-seeking as well as promoting mental health and wellbeing. Case presentation The current case study initially outlines the rigorous approach in the development of one such online intervention system, MePlusMe. It further highlights key features that constitute innovative delivery of evidence-based psychological and educational practice in the areas of mental health, promotion of wellbeing, support of mood and everyday functioning, and study-skills enhancement. Conclusions This case study aims to present the innovative features of MePlusMe in relation to current needs and evidence-basis. Finally, it presents future directions in the evaluation, assessment, and evidence of the fitness-for-purpose process

The do's, don't and don't knows of supporting transition to more independent practice

Introduction: Transitions are traditionally viewed as challenging for clinicians. Throughout medical career pathways, clinicians need to successfully navigate successive transitions as they become progressively more independent practitioners. In these guidelines, we aim to synthesize the evidence from the literature to provide guidance for supporting clinicians in their development of independence, and highlight areas for further research. Methods: Drawing upon D3 method guidance, four key themes universal to medical career transitions and progressive independence were identified by all authors through discussion and consensus from our own experience and expertise: workplace learning, independence and responsibility, mentoring and coaching, and patient perspectives. A scoping review of the literature was conducted using Medline database searches in addition to the authors’ personal archives and reference snowballing searches. Results: 387 articles were identified and screened. 210 were excluded as not relevant to medical transitions (50 at title screen; 160 at abstract screen). 177 full-text articles were assessed for eligibility; a further 107 were rejected (97 did not include career transitions in their study design; 10 were review articles; the primary references of these were screened for inclusion). 70 articles were included of which 60 provided extractable data for the final qualitative synthesis. Across the four key themes, seven do’s, two don’ts and seven don’t knows were identified, and the strength of evidence was graded for each of these recommendations. Conclusion: The two strongest messages arising from current literature are first, transitions should not be viewed as one moment in time: career trajectories are a continuum with valuable opportunities for personal and professional development throughout. Second, learning needs to be embedded in practice and learners provided with authentic and meaningful learning opportunities. In this paper, we propose evidence-based guidelines aimed at facilitating such transitions through the fostering of progressive independence

Diseño de un manual de detección de ansiedad social en adolescentes

Curso de Especial InterésEl objetivo de este trabajo de grado ha sido diseñar un manual dirigido a padres y docentes, en el que se establezcan técnicas de detección de ansiedad social en adolescentes; el diseño de este manual permite un aprendizaje significativo de una forma diferente, en un lenguaje claro y preciso, en formato digital para un fácil acceso y portabilidad del material, logrando de esta forma, que la población adolescente sea beneficiada a través de las acciones que se emprenderán por parte de los padres de familia, docentes y profesionales.142 p.RESUMEN 1. JUSTIFICACIÓN 2. OBJETIVOS 3. ESTUDIO DEL MERCADO 4. PRESENTACIÓN DEL PRODUCTO 5. CLIENTES – SEGMENTACIÓN 6. COMPETENCIA 7. CANALES DE DISTRIBUCIÓN 8. RESULTADOS DEL ESTUDIO DE MERCADO 9. DISCUSIÓN DEL ESTUDIO DE MERCADO 10. PRESUPUESTO 11. RESULTADOS 12. CONCLUSIONES REFERENCIAS APÉNDICESPregradoPsicólog

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Family violence, war, and natural disasters: A study of the effect of extreme stress on children's mental health in Sri Lanka

Catani C, Jacob N, Schauer E, Kohila M, Neuner F. Family violence, war, and natural disasters: a study of the effect of extreme stress on children's mental health in Sri Lanka. BMC Psychiatry. 2008;8(1): 33.BACKGROUND: The consequences of war violence and natural disasters on the mental health of children as well as on family dynamics remain poorly understood. Aim of the present investigation was to establish the prevalence and predictors of traumatic stress related to war, family violence and the recent Tsunami experience in children living in a region affected by a long-lasting violent conflict. In addition, the study looked at whether higher levels of war violence would be related to higher levels of violence within the family and whether this would result in higher rates of psychological problems in the affected children. METHODS: 296 Tamil school children in Sri Lanka's North-Eastern provinces were randomly selected for the survey. Diagnostic interviews were carried out by extensively trained local Master level counselors. PTSD symptoms were established by means of a validated Tamil version of the UCLA PTSD Index. Additionally, participants completed a detailed checklist of event types related to organized and family violence. RESULTS: 82.4% of the children had experienced at least one war-related event. 95.6% reported at least one aversive experience out of the family violence spectrum. The consequences are reflected in a 30.4% PTSD and a 19.6% Major Depression prevalence. Linear regression analyses showed that fathers' alcohol intake and previous exposure to war were significantly linked to the amount of maltreatment reported by the child. A clear dose-effect relationship between exposure to various stressful experiences and PTSD was found in the examined children. CONCLUSION: Data argue for a relationship between war violence and violent behavior inflicted on children in their families. Both of these factors, together with the experience of the recent Tsunami, resulted as significant predictors of PTSD in children, thus highlighting the detrimental effect that the experience of cumulative stress can have on children's mental health

Increased CCL2, CCL3, CCL5, and IL-1β cytokine concentration in piriform cortex, hippocampus, and neocortex after pilocarpine-induced seizures

BACKGROUND: Cytokines and chemokines play an important role in the neuroinflammatory response to an initial precipitating injury such as status epilepticus (SE). These signaling molecules participate in recruitment of immune cells, including brain macrophages (microglia), as well as neuroplastic changes, deterioration of damaged tissue, and epileptogenesis. This study describes the temporal and brain region pattern expression of numerous cytokines, including chemokines, after pilocarpine-induced seizures and discusses them in the larger context of their potential involvement in the changes that precede the development of epilepsy. FINDINGS: Adult rats received pilocarpine to induce SE and 90 min after seizure onset were treated with diazepam to mitigate seizures. Rats were subsequently deeply anesthetized and brain regions (hippocampus, piriform cortex, neocortex, and cerebellum) were freshly dissected at 2, 6, and 24 h or 5 days after seizures. Using methodology identical to our previous studies, simultaneous assay of multiple cytokines (CCL2, CCL3, CCL5, interleukin IL-1β, tumor necrosis factor (TNF-α)), and vascular endothelial growth factor (VEGF) was performed and compared to control rats. These proteins were selected based on existing evidence implicating them in the epileptogenic progression. A robust increase in CCL2 and CCL3 concentrations in the hippocampus, piriform cortex, and neocortex was observed at all time-points. The concentrations peaked with a ~200-fold increase 24 h after seizures and were two orders of magnitude greater than the significant increases observed for CCL5 and IL-1β in the same brain structures. TNF-α levels were altered in the piriform cortex and neocortex (24 h) and in the hippocampus (5 days) after SE. CONCLUSIONS: Pilocarpine-induced status epilepticus causes a rapid increase of multiple cytokines in limbic and neocortical regions. Understanding the precise spatial and temporal pattern of cytokines and chemokine changes could provide more viable therapeutic targets to reduce, reverse, or prevent the development of epilepsy following a precipitating injury

In Vivo Evaluation of the Biocompatibility of Surface Modified Hemodialysis Polysulfone Hollow Fibers in Rat

Polysulfone (Psf) hollow fiber membranes (HFMs) have been widely used in blood purification but their biocompatibility remains a concern. To enhance their biocompatibility, Psf/TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate) composite HFMs and 2-methacryloyloxyethyl phosphorylcholine (MPC) coated Psf HFMs have been prepared. They have been evaluated for in vivo biocompatibility and graft acceptance and compared with sham and commercial membranes by intra-peritoneal implantation in rats at day 7 and 21. Normal body weights, tissue formation and angiogenesis indicate acceptance of implants by the animals. Hematological observations show presence of post-surgical stress which subsides over time. Serum biochemistry results reveal normal organ function and elevated liver ALP levels at day 21. Histological studies exhibit fibroblast recruitment cells, angiogenesis and collagen deposition at the implant surface indicating new tissue formation. Immuno-histochemistry studies show non-activation of MHC molecules signifying biocompatibilty. Additionally, Psf/TPGS exhibit most favorable tissue response as compared with other HFMs making them the material of choice for HFM preparation for hemodialysis applications

Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents.</p> <p>Methods</p> <p>Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment.</p> <p>Results</p> <p>Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034).</p> <p>Conclusions</p> <p>Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM.</p