Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial

Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. Methods/design The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH2O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH2O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. Discussion To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. Trial registration ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1929-0) contains supplementary material, which is available to authorized users

Brede opleiding sociaal werk is te eenzijdig

Moeten de opleidingen sociaal werk op de hogescholen nu wel of niet samengevoegd worden? Ja, betoogden auteurs hier, de samenleving vraagt om breed inzetbare professionals. Maar Judith Metz en collega’s slaat de schrik om het hart, want: wat blijft er dan over van de professionaliteit

Survival of short hip stems with a "modern", trochanter-sparing design - a systematic literature review

Modern total hip arthroplasty delivers excellent and reproducible results. New implant developments include a wide range of implants with a bone and tissue sparing design, including short femoral stems. This review was performed to provide an overview on the currently published survival results of short stems to allow comparison with the results of traditional hip stems. A literature search was performed to identify publications on short stems with a "modern" trochanter sparing design including implant survival information. Information was collected on the study population, follow-up time, implants used, implant survival and functional scores. The revision rate per 100 observed component years was calculated and compared to data presented in national arthroplasty registries. The methodological quality was assessed by employing a score specific to survival assessment of hip stems. In the course of 16 individual searches in EMBASE and Medline, 460 potentially eligible articles were identified. After thorough screening, 14 articles were deemed applicable. The variability in quality of the publications was high. No association between survival outcome and publication quality was apparent. The total revision rate over all studies was found to be 0.38 per 100 component years with endpoint "stem revision for any reason". The survival rate of these stems is encouraging and appears to be comparable with that of more traditional uncemented stems. However, only few mid-term and long-term studies are available. Reports with longer follow-up are needed to draw further conclusions

Safety and efficacy of epidural analgesia

Purpose of reviewEpidural analgesia remains a widely used analgesic technique. This article aims to assess the safety of epidural analgesia by balancing efficacy and complications, of epidural analgesia for acute, labor and chronic pain.Recent findingsMain indications for epidural analgesia include major open abdominal surgery, thoracotomy and labor analgesia. Past and current literature show that epidural analgesia leads to statistically significant, but possibly clinically less meaningful, reductions in pain scores compared with intravenous analgesia. The debate continues whether epidural analgesia leads to decreased complications and improved outcome. Noninferiority of alternative regional analgesic approaches, that is continuous-wound-infiltration, peripheral nerve blocks or surgical site infiltration, appears to be present and is promising for the future. Serious adverse events after epidural analgesia seem to occur more often than was previously thought and clinicians must realize that incidence rates differ in specific perioperative patient populations.SummaryEpidural analgesia for obstetric analgesic purposes is considered to be well tolerated in young, healthy women, since efficacy has been proven and complications leading to permanent neurological damage seldomly occur. Safety of epidural analgesia for perioperative and chronic pain treatment is more difficult to balance; careful selection of appropriate patients cannot be over-emphasize

The laminated glass column

A transparent column, consisting of two glass tubes laminated with a clear resin, has been developed during several years of ZAPPI research. Intensive testing led to a lamination process for columns on a scale relevant to building structures with close to perfect results. Compression tests showed safe, gradual and controlled failure behaviour compatible with the ZAPPI safety philosophy. This prescribes safe failure behaviour of transparent structural components rather than using gross over dimensioning to achieve safety. The composition of the column and the results of compression testing are discussed

The joints for the all transparent pavilion

Several innovative joints have been applied in the All Transparent Pavilion. Methods to connect annealed glass are sought, because the ordinary bolted pin joints are not possible in non-tempered glass. The other goal was to optimize transparency. The joints were subjected to different quantities of experiment before they were applied in the mounting of the pavilion. The designs as well as the experiments on four joints are described

Language processing in glioma patients: speed or accuracy as a sensitive measure?

Background: Glioma (brain tumour) patients can suffer from mild linguistic and non-linguistic cognitive problems when the glioma is localised in an eloquent brain area. Word-finding problems are among the most frequently reported complaints. However, mild problems are difficult to measure with standard language tests because they are generally designed for more severe aphasic patients. Aims: The aim of the present study was to investigate whether word-finding problems reported by patients with a glioma can be objectified with a standard object naming test, and a linguistic processing speed test. In addition, we examined whether word-finding problems and linguistic processing speed are related to non-verbal cognitive abilities. Methods & Procedures: We tested glioma patients (N=36) as part of their standard pre-treatment clinical work-up. Word-finding problems were identified by a clinical linguist during the anamnesis. Linguistic processing speed was assessed with a newly designed sentence judgment test (SJT) as part of the Diagnostic Instrument for Mild Aphasia (DIMA), lexical retrieval with the Boston Naming Test (BNT), presence of aphasia with a Token Test (TT), and non-verbal processing with the Trail Making Test A and B (TMT). Test performances of glioma patients were compared to those of healthy control participants (N=35). Outcomes & Results: The results show that many glioma patients (58%) report word-finding problems; these complaints were in only half of the cases supported by deviant scores on the BNT. Moreover, the presence of reported word-finding problems did not correlate with the BNT scores. However, word-finding problems were significantly correlated with reaction times on the SJT and the TMT. Although there were no significant differences between the patient and control group on the SJT, a subgroup of patients with a glioma in the frontal lobe of the language-dominant hemisphere was slower on the SJT. Finally, performance on the SJT and TMT were significantly correlated in the patient group but not in the control group. Conclusions: Linguistic processing speed appears to be an important factor in explaining reported word-finding problems. Moreover, the overlap between speed of language processing and non-verbal processing indicates that patients may rely on more domain-general cognitive abilities as compared to healthy participants. The variability observed between patients emphasises the need for tailored neuro-linguistic assessments including an extensive anamnesis regarding language problems in clinical work-up