Inhibition of NF-kB 1 (NF-kBp50) by RNA interference in chicken macrophage HD11 cell line challenged with Salmonellaenteritidis

The NF-kB pathway plays an important role in regulating the immunity response in animals. In this study, small interfering RNAs (siRNA) were used to specifically inhibit NF-kB 1 expression and to elucidate the role of NF-kB in the signal transduction pathway of the Salmonella challenge in the chicken HD11 cell line. The cells were transfected with either NF-kB 1 siRNA, glyceraldehyde 3-phosphate dehydrogenase siRNA (positive control) or the negative control siRNA for 24 h, followed by Salmonella enteritidis (SE) challenge or non-challenge for 1 h and 4 h. Eight candidate genes related to the signal pathway of SE challenge were selected to examine the effect of NF-kB 1 inhibition on their expressions by mRNA quantification. The results showed that, with a 36% inhibition of NF-kB 1 expression, gene expression of both Toll-like receptor (TLR) 4 and interleukin (IL)-6 was consistently and significantly increased at both 1 h and 4 h following SE challenge, whereas the gene expression of MyD88 and IL-1β was increased at 1 h and 4 h, respectively. These findings suggest a likely inhibitory regulation by NF-kB 1, and could lay the foundation for studying the gene network of the innate immune response of SE infection in chickens

Family Relationship, Water Contact and Occurrence of Buruli Ulcer in Benin

Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities. This case control study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU). The study involved 416 participants, of which 104 BU-confirmed cases and 312 age, gender and village of residence matched controls (persons who had no signs or symptoms of active or inactive BU). The results confirmed that contact with natural water sources is a risk factor. Furthermore, it suggests that a combination of genetic factors may constitute risk factors for the development of BU, possibly by influencing the type of immune response in the individual, and, consequently, the development of BU infection per se and its different clinical forms. These findings may be of major therapeutic interest

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Clinical Events After Deferral of LAD Revascularization Following Physiological Coronary Assessment

BACKGROUND Physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR). OBJECTIVES The purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial. METHODS MACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex. RESULTS A total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06). CONCLUSIONS iFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral. (c) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Grey wolf genomic history reveals a dual ancestry of dogs

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canisfamiliaris) lived(1-8). Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT8840,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.Peer reviewe

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Uitdagingen rond de therapietrouw van adolescenten

Non-adherence occurs at any age, in all chronic diseases, and has a major impact on clinical outcomes. Non-adherence is primarily determined by perceptions of illness and medication beliefs. During puberty, adolescents attain independence from their parents and attach to their peers. This complicates successful self-management of chronic illness, because the adolescents avoid standing out from their peers. Discussion of barriers hindering successful self-management in adolescents can be promoted by seeing the patient alone, without the parents being present, and by acknowledging the patient's independence and responsibilities

Monimuotoistuvat työyhteisöt : lievästi kehitysvammaiset puhtausalan työntekijöinä

Opinnäytetyön tavoitteena on selvittää miten yksityinen palvelualan yritys voi työllistää lievästi kehitysvammaisia tulevaisuudessa entistä enemmän puhtausalan työtehtäviin. Tulevina vuosina työikäisen väestön väheneminen aiheuttaa työvoimapulaa. Työmarkkinoiden ulkopuolella on lievästi kehitysvammaisia, jotka haluaisivat työhön. Heidän työllistämisensä voisi auttaa myös tulevassa työvoimapulassa. Työn tavoitteena on selvittää miten yrityksessä voidaan työllistää lievästi kehitysvammaisia henkilöitä sekä miten heidät pitäisi huomioida työn organisoinnissa, johtamisessa ja ohjaamisessa. Tässä työssä ei käsitellä erilaisia yhteiskunnalta saatavia tukia. Opinnäytetyö on laadullinen tutkimus, jossa aineistoa kerättiin yrityksessä tehdyillä puolistrukturoiduilla teemahaastatteluilla. Selvityksen tuloksissa tuli esille, että lievästi kehitysvammaisten työllistäminen on mahdollista yrityksessä. Se vaatii kuitenkin hyvää valmistelua, valmennusta ja työjärjestelyjä.The objective of this thesis is to clarify how the private service business can employ the mildly retarded people more than now in cleaning services. In the coming years, the working-age population is going to decrease and it causes the shortage of manpower. Outside of the labor market there are the mildly retarded people, who like to work. It could also help in the shortage of manpower if the company employ them in future. The objective of the thesis is to clarify how the company can employ the mildly retarded people and how they should be noticed in the organization of the work, in the management and in the instruction. In this work there is no processing of the supports which the employers can get from society. The thesis is the qualitative research and the material was collected with half structured theme interviews which were taped in the company. The results of the report were that it is possible to employ the mildly retarded people in the company. However, it needs good preparation, training and working arrangements

The SABRE Trial (Sirolimus Angioplasty Balloon for Coronary In-Stent Restenosis) : Angiographic Results and 1-Year Clinical Outcomes

Objectives The aim of this first-in-human study was to assess the safety and effectiveness of the Virtue sirolimus-eluting balloon in a cohort of patients with in-stent restenosis (ISR). Background Angioplasty balloons coated with the cytotoxic drug paclitaxel have been widely used for ISR treatment. The Virtue angioplasty balloon (Caliber Therapeutics, New Hope, Pennsylvania) delivers sirolimus in a nanoencapsulated liquid formulation. This clinical trial is the first to examine a sirolimus-eluting balloon for ISR. Methods In this prospective, single-arm feasibility study at 9 European centers, 50 ISR patients were treated with the Virtue balloon. Angiographic measurements at 6 months are reported, along with 12-month clinical follow-up. Results Procedural success in the intention-to-treat population was 100%. The primary safety endpoint was target lesion failure (TLF) (cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization) assessed at 30 days (0%, n = 50). The primary performance endpoint was in-segment late lumen loss (LLL) at 6 months (0.31 ± 0.52 mm; n = 47). Secondary 6-month endpoints include binary restenosis (19.1%), diameter stenosis (30.3 ± 19.9%), and major adverse cardiac events (MACE) (10.2%, n = 49). In the 36-patient per-protocol population (excluding major protocol violations and previously stented ISR), LLL was 0.12 ± 0.33 mm at 6 months. Clinical outcomes at 1 year for the intention-to-treat group were 12.2% TLF and 14.3% MACE and for the per-protocol population were 2.8% TLF and 2.8% MACE. Conclusions This first-in-human study showed excellent procedural success for the Virtue sirolimus-eluting angioplasty balloon, 6-month LLL rates in line with current stent-free ISR treatment options, and clinical outcomes that warrant further evaluation in dedicated randomized studies