Epidemiology of traumatic brain injury in Europe

Background: Traumatic brain injury (TBI) is a critical public health and socio-economic problem throughout the world, making epidemiological monitoring of incidence, prevalence and outcome of TBI necessary. We aimed to describe the epidemiology of traumatic brain injury in Europe and to evaluate the methodology of incidence studies. Method: We performed a systematic review and meta-analyses of articles describing the epidemiology of TBI in European countries. A search was conducted in the PubMed electronic database using the terms: epidemiology, incidence, brain injur*, head injur* and Europe. Only articles published in English and reporting on data collected in Europe between 1990 and 2014 were included. Results: In total, 28 epidemiological studies on TBI from 16 European countries were identified in the literature. A great variation was found in case definitions and case ascertainment between studies. Falls and road traffic accidents (RTA) were the two most frequent causes of TBI, with falls being reported more frequently than RTA. In most of the studies a peak TBI incidence was seen in the oldest age groups. In the meta-analysis, an overall incidence rate of 262 per 100,000 for admitted TBI was derived. Conclusions: Interpretation of published epidemiologic studies is confounded by differences in inclusion criteria and case ascertainment. Nevertheless, changes in epidemiological patterns are found: falls are now the most common cause of TBI, most notably in elderly patients. Improvement of the quality of standardised data collection for TBI is mandatory for reliable monitoring of epidemiological trends and to inform appropriate targeting of prevention campaigns

Phosphonium-based polythiophene conjugated polyelectrolytes with different surfactant counterions: thermal properties, self-assembly and photovoltaic performances

© 2020 Society of Industrial Chemistry Phosphonium-based polythiophene conjugated polyelectrolytes (CPEs) with three different counterions (dodecylsulfate, octylsulfate and perfluorooctane sulfonate) are synthesized to determine how the nature of the counterion affects the thermal properties, the self-assembly in thin films and the performance as the cathode interfacial layer in polymer solar cells (PSCs). The counterion has a significant effect on the thermal properties of the CPEs, affecting both their glass transition and crystalline behaviour. Grazing-incidence wide-angle X-ray scattering studies also indicate that changing the nature of the counterion influences the microstructural organization in thin films (face-on versus edge-on orientation). The affinity of the CPEs with the underlying photoactive layer in PSCs is highly correlated with the counterion species. Finally, in addition to an increase of the power conversion efficiency of ca 15% when using these CPEs as cathode interfacial layers in PSCs, a higher device stability is noted, compared to a reference device with a calcium interlayer. © 2020 Society of Industrial Chemistry

Self-assembled conjugated polyelectrolyte-surfactant complexes as efficient cathode interlayer materials for bulk heterojunction organic solar cells

Conjugated polyelectrolyte–surfactant cathodic interface layers lead to improved power conversion efficiencies in organic solar cells.</p

Probiotic Sonicates Selectively Induce Mucosal Immune Cells Apoptosis through Ceramide Generation via Neutral Sphingomyelinase

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Probiotics appear to be beneficial in inflammatory bowel disease, but their mechanism of action is incompletely understood. We investigated whether probiotic-derived sphingomyelinase mediates this beneficial effect. [Methodology/Principal Findings]: Neutral sphingomyelinase (NSMase) activity was measured in sonicates of the probiotic L. brevis (LB) and S. thermophilus (ST) and the non-probiotic E. coli (EC) and E. faecalis (EF). Lamina propria mononuclear cells (LPMC) were obtained from patients with Crohn's disease (CD) and Ulcerative Colitis (UC), and peripheral blood mononuclear cells (PBMC) from healthy volunteers, analysing LPMC and PBMC apoptosis susceptibility, reactive oxygen species (ROS) generation and JNK activation. In some experiments, sonicates were preincubated with GSH or GW4869, a specific NSMase inhibitor. NSMase activity of LB and ST was 10-fold that of EC and EF sonicates. LB and ST sonicates induced significantly more apoptosis of CD and UC than control LPMC, whereas EC and EF sonicates failed to induce apoptosis. Pre-stimulation with anti-CD3/CD28 induced a significant and time-dependent increase in LB-induced apoptosis of LPMC and PBMC. Exposure to LB sonicates resulted in JNK activation and ROS production by LPMC. NSMase activity of LB sonicates was completely abrogated by GW4869, causing a dose-dependent reduction of LB-induced apoptosis. LB and ST selectively induced immune cell apoptosis, an effect dependent on the degree of cell activation and mediated by bacterial NSMase. [Conclusions]: These results suggest that induction of immune cell apoptosis is a mechanism of action of some probiotics, and that NSMase-mediated ceramide generation contributes to the therapeutic effects of probiotics.The funding sources included grants from Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Ministerio de Ciencia e Innovación (SAF2005-00280 and SAF2008-03676 to MS, FIS2009-00056 to AM, SAF2009-11417 to JCF), Fundación Ramón Areces (to MS), the National Institutes of Health (DK30399 and DK50984 to CF) and the Research Center for Liver and Pancreatic Diseases funded by the United States National Institute for Alcohol Abuse and Alcoholism (P50 AA 11999 to JCF).Peer reviewe

Tuberculosis screening and follow-up of asylum seekers in Norway: a cohort study

<p>Abstract</p> <p>Background</p> <p>About 80% of new tuberculosis cases in Norway occur among immigrants from high incidence countries. On arrival to the country all asylum seekers are screened with Mantoux test and chest x-ray aimed to identify cases of active tuberculosis and, in the case of latent tuberculosis, to offer follow-up or prophylactic treatment.</p> <p>We assessed a national programme for screening, treatment and follow-up of tuberculosis infection and disease in a cohort of asylum seekers.</p> <p>Methods</p> <p>Asylum seekers ≥ 18 years who arrived at the National Reception Centre from January 2005 to June 2006, were included as the total cohort. Those with a Mantoux test ≥ 6 mm or positive x-ray findings were included in a study group for follow-up.</p> <p>Data were collected from public health authorities in the municipality to where the asylum seekers had moved, and from hospital based internists in case they had been referred to specialist care.</p> <p>Individual subjects included in the study group were matched with the Norwegian National Tuberculosis Register which receive reports of everybody diagnosed with active tuberculosis, or who had started treatment for latent tuberculosis.</p> <p>Results</p> <p>The total cohort included 4643 adult asylum seekers and 97.5% had a valid Mantoux test. At least one inclusion criterion was fulfilled by 2237 persons. By end 2007 municipal public health authorities had assessed 758 (34%) of them. Altogether 328 persons had been seen by an internist. Of 314 individuals with positive x-rays, 194 (62%) had seen an internist, while 86 of 568 with Mantoux ≥ 15, but negative x-rays (16%) were also seen by an internist. By December 31^st2006, 23 patients were diagnosed with tuberculosis (prevalence 1028/100 000) and another 11 were treated for latent infection.</p> <p>Conclusion</p> <p>The coverage of screening was satisfactory, but fewer subjects than could have been expected from the national guidelines were followed up in the community and referred to an internist. To improve follow-up of screening results, a simplification of organisation and guidelines, introduction of quality assurance systems, and better coordination between authorities and between different levels of health care are all required.</p

Phase II trial of oral S-1 combined with gemcitabine in metastatic pancreatic cancer

We conducted a phase II trial of gemcitabine with S-1, oral fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate, to evaluate the activity and toxicity of such a combination in metastatic pancreatic cancer (MPC) patients. Patients who had pathologically proven pancreatic cancer with metastatic lesions were eligible candidates for entry into the study. S-1 was given orally (30 mg m−2) b.i.d. for 14 consecutive days and gemcitabine (1000 mg m−2) was given on days 8 and 15. The cycle was repeated every 21 days. We enrolled 33 MPC patients. The median number of cycles was eight (range 1–20). Grade 3–4 toxicities were leucopenia (33%), neutropenia (55%), anaemia (9%), thrombocytopenia (15%), anorexia (6%), fever (9%), and interstitial pneumonia (6%). Objective responses were obtained in 16 patients (one complete response and 15 partial responses; response rate, 48%; 95% confidence interval (CI), 33–65). Median survival and 1-year survival rate were 12.5 months (95% CI, 5.9–19.1) and 54% (95% CI, 36–72), respectively. Combination chemotherapy with GEM and S-1 was well tolerated and yielded a significantly high response rate

On the genetic involvement of apoptosis-related genes in Crohn's disease as revealed by an extended association screen using 245 markers: no evidence for new predisposing factors

Crohn's disease (CD) presents as an inflammatory barrier disease with characteristic destructive processes in the intestinal wall. Although the pathomechanisms of CD are still not exactly understood, there is evidence that, in addition to e.g. bacterial colonisation, genetic predisposition contributes to the development of CD. In order to search for predisposing genetic factors we scrutinised 245 microsatellite markers in a population-based linkage mapping study. These microsatellites cover gene loci the encoded protein of which take part in the regulation of apoptosis and (innate) immune processes. Respective loci contribute to the activation/suppression of apoptosis, are involved in signal transduction and cell cycle regulators or they belong to the tumor necrosis factor superfamily, caspase related genes or the BCL2 family. Furthermore, several cytokines as well as chemokines were included. The approach is based on three steps: analyzing pooled DNAs of patients and controls, verification of significantly differing microsatellite markers by genotyping individual DNA samples and, finally, additional reinvestigation of the respective gene in the region covered by the associated microsatellite by analysing single-nucleotide polymorphisms (SNPs). Using this step-wise process we were unable to demonstrate evidence for genetic predisposition of the chosen apoptosis- and immunity-related genes with respect to susceptibility for CD

The role of entry screening in case finding of tuberculosis among asylum seekers in Norway

<p>Abstract</p> <p>Background</p> <p>Most new cases of active tuberculosis in Norway are presently caused by imported strains and not transmission within the country. Screening for tuberculosis with a Mantoux test of everybody and a chest X-ray of those above 15 years of age is compulsory on arrival for asylum seekers.</p> <p>We aimed to assess the effectiveness of entry screening of a cohort of asylum seekers. Cases detected by screening were compared with cases detected later. Further we have characterized cases with active tuberculosis.</p> <p>Methods</p> <p>All asylum seekers who arrived at the National Reception Centre between January 2005 - June 2006 with an abnormal chest X-ray or a Mantoux test ≥ 6 mm were included in the study and followed through the health care system. They were matched with the National Tuberculosis Register by the end of May 2008.</p> <p>Cases reported within two months after arrival were defined as being detected by screening.</p> <p>Results</p> <p>Of 4643 eligible asylum seekers, 2237 were included in the study. Altogether 2077 persons had a Mantoux ≥ 6 mm and 314 had an abnormal chest X-ray. Of 28 cases with tuberculosis, 15 were detected by screening, and 13 at 4-27 months after arrival. Abnormal X-rays on arrival were more prevalent among those detected by screening. Female gender and Somalian origin increased the risk for active TB.</p> <p>Conclusion</p> <p>In spite of an imperfect follow-up of screening results, a reasonable number of TB cases was identified by the programme, with a predominance of pulmonary TB.</p

A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours

The aim of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and the pharmacokinetic profile (Pk) of bendamustine (BM) on a day 1 and 2 every 3 weeks schedule and to recommend a safe phase II dose for further testing. Patients with solid tumours beyond standard therapy were eligible. A 30-min intravenous infusion of BM was administered d1+d2 q 3 weeks. The starting dose was 120 mg m−2 per day and dose increments of 20 mg m−2 were used. Plasma and urine samples were analysed using validated high-performance liquid chromatography/fluorescence assays. Fifteen patients were enrolled. They received a median of two cycles (range 1–8). The MTD was reached at the fourth dose level. Thrombocytopaenia (grade 4) was dose limiting in two of three patients at 180 mg m−2. One patient also experienced febrile neutropaenia. Lymphocytopaenia (grade 4) was present in every patient. Nonhaematologic toxicity including cardiac toxicity was not dose limiting with this schedule. Mean plasma Pk values of BM were tmax 35 min, t1/2 49.1 min, Vd 18.3 l m−2, and clearance 265 ml min−1 m−2. The mean total amount of BM and its metabolites recovered in the first micturition was 8.3% (range 2.7–26%). The MTD of BM in the present dose schedule was 180 mg m−2 on day 1+2. Thrombocytopaenia was dose limiting. The recommended dose for future phase II trials with this schedule is 160 mg m−2 per day

Phase I trial of oral S-1 combined with gemcitabine in metastatic pancreatic cancer

The objective of this study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of S-1, an oral fluorouracil derivative, combined with gemcitabine, the current standard treatment for advanced pancreatic cancer (APC). The subjects were histopathologically proven APC patients with distant metastasis. S-1 was administered orally twice daily each day for 14 days and gemcitabine on days 8 and 15 of each cycle, and this was repeated every 21 days. Doses of each drug were planned as follows: level 1: 800/60, level 2a: 800/80, level 2b: 1000/60, level 3: 1000/80 (gemcitabine (mg m−2)/S-1 (mg m−2 day−1)). In all, 21 patients with APC were enrolled. The main grade 3–4 toxicities observed during first cycle were neutropenia (33%), anaemia (10%), thrombocytopenia (14%) and anorexia (10%). There were no DLT observed in level 1. Three of six patients in level 2a had DLT and this level was considered the MTD. In all, 12 patients in level 2b had no DLT and this level was selected as the recommended dose. Applicable responses were one complete response and nine partial responses (48%). As toxicities were well tolerated and antitumour activities seem to be promising, this combination can be recommended for further phase II studies with APC