Abstract Background In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are ...larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that experimental tethering alone increases mitral valve area in association with endothelial-to-mesenchymal transition. Objectives The aim of this study was to explore the clinically relevant situation of tethering and MI, testing the hypothesis that ischemic milieu modifies mitral valve adaptation. Methods Twenty-three adult sheep were examined. Under cardiopulmonary bypass, the papillary muscle tips in 6 sheep were retracted apically to replicate tethering, short of producing MR (tethered alone). Papillary muscle retraction was combined with apical MI created by coronary ligation in another 6 sheep (tethered plus MI), and left ventricular remodeling was limited by external constraint in 5 additional sheep (left ventricular constraint). Six sham-operated sheep were control subjects. Diastolic mitral valve surface area was quantified by 3-dimensional echocardiography at baseline and after 58 ± 5 days, followed by histopathology and flow cytometry of excised leaflets. Results Tethered plus MI leaflets were markedly thicker than tethered-alone valves and sham control subjects. Leaflet area also increased significantly. Endothelial-to-mesenchymal transition, detected as α-smooth muscle actin-positive endothelial cells, significantly exceeded that in tethered-alone and control valves. Transforming growth factor-β, matrix metalloproteinase expression, and cellular proliferation were markedly increased. Uniquely, tethering plus MI showed endothelial activation with vascular adhesion molecule expression, neovascularization, and cells positive for CD45, considered a hematopoietic cell marker. Tethered plus MI findings were comparable with external ventricular constraint. Conclusions MI altered leaflet adaptation, including a profibrotic increase in valvular cell activation, CD45-positive cells, and matrix turnover. Understanding cellular and molecular mechanisms underlying leaflet adaptation and fibrosis could yield new therapeutic opportunities for reducing ischemic MR.
Germline mutations of the BRCA tumour suppressors have been associated with increased risk of pancreatic cancer. Clinical evidence suggests that these patients may be more sensitive to treatment with ...cisplatin. As the frequency of germline BRCA mutations is low, definitive experimental data to support the clinical observations are still missing.
We tested gemcitabine and cisplatin sensitivity of four BRCA1 and BRCA2 mutant and three BRCA1 and BRCA2 wild-type (WT) patient-derived pancreatic cancer xenografts.
We observed treatment sensitivity to gemcitabine and cisplatin in the BRCA WT and mutant models. The BRCA1 and BRCA2 mutant xenografts were significantly more sensitive to cisplatin although these models also showed sensitivity to gemcitabine. The BRCA1 and BRCA2 WT models showed sensitivity to gemcitabine but not cisplatin. Treatment sensitivity in the xenograft models closely resembled treatment response in the corresponding patients.
We have characterised a panel of xenografts derived from pancreatic cancer patients carrying germline BRCA mutations, and shown that their genetic features resemble the patient donor. Our results support further clinical testing of treatment regimens combining gemcitabine and platinum drugs in this patient population, as well as preclinical research aiming to identify mechanisms of cisplatin resistance in BRCA mutant pancreatic cancers.
Highly-pathogenic avian influenza virus (HPAIV) H5N6 (clade 2.3.4.4b) incurred into Europe in late 2017 and was predominantly detected in wild birds, with very few terrestrial poultry cases. Pekin ...ducks directly-infected with a UK virus (H5N6-2017) were donors of infection to investigate contact transmission to three recipient species: Ducks, chickens and turkeys. H5N6-2017 transmission to ducks was 100% efficient, but transmission to in-contact galliforme species was infrequent and unpredictable, thereby reflecting the European 2017–2018 H5N6 epidemiology. Although only two of 28 (7%) infected ducks died, the six turkeys and one chicken which became infected all died and displayed systemic H5N6-2017 dissemination, while pathogenesis in ducks was generally milder. Analysis of H5N6-2017 progeny in the contacts revealed no emergent polymorphisms in an infected duck, but the galliforme species included changes in the polymerase (PB2 A199T, PA D347A), matrix (M1 T218A) and neuraminidase genes (T88I). H5N6-2017 environmental contamination was associated with duck shedding.
•Modelled waterfowl / terrestrial poultry interface for introduction of H5N6 (clade 2.3.4.4) HPAIV.•No viral genetic polymorphisms emerged during efficient transmission among ducks.•Transmission from ducks to chickens and turkeys was inefficient or sporadic, with different pathogenesis outcomes.•Polymorphisms (including in the viral polymerase genes) emerged during transmission from ducks to a turkey.•H5N6 HPAIV environmental contamination occurred during duck viral shedding and may have a role in local viral spread.
Large observational studies have shown that small, dense LDL subfractions are related to atherosclerotic cardiovascular disease. This study assessed the effects of two highly effective lipid-lowering ...therapies in the atherogenic subclasses of lipoproteins in subjects with ST-segment elevation myocardial infarction (STEMI).
Patients of both sexes admitted with their first myocardial infarction and submitted to pharmacoinvasive strategy (N = 101) were included and randomized using a central computerized system to receive a daily dose of simvastatin 40 mg plus ezetimibe 10 mg or rosuvastatin 20 mg for 30 days. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) subfractions were analysed by polyacrylamide gel electrophoresis (Lipoprint System) on the first (D1) and 30th days (D30) of lipid-lowering therapy. Changes in LDL and IDL subfractions between D1 and D30 were compared between the lipid-lowering therapies (Mann-Whitney U test).
The classic lipid profile was similar in both therapy arms at D1 and D30. At D30, the achievement of lipid goals was comparable between lipid-lowering therapies. Cholesterol content in atherogenic subclasses of LDL (p = 0.043) and IDL (p = 0.047) decreased more efficiently with simvastatin plus ezetimibe than with rosuvastatin.
Lipid-lowering therapy with simvastatin plus ezetimibe was associated with a better pattern of lipoprotein subfractions than rosuvastatin monotherapy. This finding was noted despite similar effects in the classic lipid profile and may contribute to residual cardiovascular risk.
ClinicalTrials.gov , NCT02428374, registered on 28/09/2014.
•Practices on animal health monitoring have been investigated.•We focused on Informational Resources that farmers use to pilot animal health.•Six types of informational resources are used by farmers ...and cited by their advisors.•Farmers primarily use informal sensory indicators based on daily herd observations.•Under-estimated sensory indicators could lead to a gap of communication.
Managers of health in livestock systems are asked to shift from a curative approach to a more preventive approach. This change requires sociological and technical reconfiguration and raises the issue of how changes are implemented by farmers and their technical support ecosystem (advisors, trainers, veterinarians). Here, we report work conducted in western France by an Agricultural European Innovation Partnership Operational Group bringing together animal scientists and sociologists to advance knowledge on animal health in a range of livestock sectors, i.e. dairy cattle, beef cattle, small ruminants (sheep, goats), poultry and pigs. In this study, our aim was to answer this question: what are the Informational Resources (I.R.) that farmers use to promote animal health of their herds? First, we used a survey to characterize 129 I.R. used by advisors, then, we used statistical analysis to classify these I.R. into six clusters. Second, we organized eight focus-group sessions that involved a total of 50 farmers from across all livestock sectors to find out how they mobilize the I.R. and what they see as important for animal health monitoring practice. Finally, we performed individual interviews with 42 farmers to expand the data captured in the collective focus groups. Results showed that farmers and advisors have a broad and diverse range of I.R. to help monitor animal health. We identified six clusters of I.R.: regulatory tools, periodic reports, tools for farmer-led monitoring, tools and indicators for national reference datasets, slaughterhouse and laboratory indicators, and training delivered to farmers. During focus group, livestock farmers identified some of their I.R. within these clusters but they also cited other daily routines that help them monitor animal health that were not cited by advisors. We found that farmers mainly use sensory indicators (typically smell, sight, touch) in their daily practice whereas advisors mainly use relatively sophisticated retrospective monitoring tools. Farmers also cited the importance of indicators that can rapidly objectify any change in animal condition, behavior, or health. This work finds a split in the distribution of animal health management roles, with farmers implementing daily checks whereas advisors run periodic health surveillance, thus revealing differentiated roles and needs between farmers and their advisors.
Xanthomonas vesicatoria (Xv) is a member of a species complex that causes bacterial spot on tomato, one of the most important diseases of this crop worldwide. The objective of this investigation was ...to analyse several characteristics involved in Xv virulence in relation to strain aggressiveness. Motility, biofilm formation, adhesion and production of xanthan were evaluated in three local strains causing tomato bacterial spot in Argentina. The strains assayed presented differential swarming and twitching motilities, adhesion and biofilm formation abilities. The most aggressive strain, BNM 208, exhibited the greatest swarming and twitching motilities, and developed a mature biofilm with presence of defined cell clusters, a homogeneous and compact structure, and higher biomass and substratum coverage than the other two strains. Even though the three strains produced similar amounts of xanthan, BNM 208 produced the most viscous exopolysaccharide, which possibly relates to the better characteristics of its biofilm. Despite other differences, the three strains multiplied to similar levels when they were infiltrated into the leaf. The results suggest that the aggressiveness of Xv strains studied in this work was related to their ability to move by flagella or type IV pili, adhere to leaves and form well developed biofilms, factors that improve phyllosphere colonization. A better understanding of the factors involved in the Xv infection process at the early stages would contribute to developing new control strategies for this phytopathogen.
Thoracic esophageal diverticula are uncommon, and controversies exist regarding their management. The objective of this study was to evaluate the outcomes of a relatively large cohort of patients ...with thoracic esophageal diverticula treated with minimally invasive surgical techniques.
We conducted a retrospective review of patients who underwent minimally invasive surgical treatment for symptomatic esophageal diverticula during a 15-year period. The primary end point was 30-day mortality. In addition, we evaluated the morbidity, improvement in dysphagia (score: 1, best to 5, worst), and quality of life (Gastroesophageal Reflux Disease-Health-Related Quality of Life score: 0, best to 50, most symptoms).
Fifty-seven patients underwent minimally invasive surgical treatment of symptomatic thoracic esophageal diverticula. The most common symptom was dysphagia (45 of 57; 79%). A motility disorder or distal mechanical obstruction was identified in 49 patients (86%). Approaches used included video-assisted thoracoscopic surgery (n = 33), laparoscopy (n = 18), and combined video-assisted thoracoscopic surgery and laparoscopy (n = 6). The most common procedure performed was diverticulectomy and myotomy (47 of 57 patients; 82.5%). The 30-day mortality was 0%. There were 4 patients (7%) with postoperative leaks requiring reoperation. During follow-up, the median dysphagia score improved from 3 to 1 (p < 0.001). The median Gastroesophageal Reflux Disease-Health-Related Quality of Life score after surgery was 5 (excellent).
A minimally invasive surgical approach for the management of thoracic esophageal diverticula is safe and effective during intermediate-term follow-up when performed by surgeons experienced in esophageal surgery and minimally invasive techniques. Further follow-up is required to assess the durability of these results. The optimal approach and procedures performed should be determined on an individualized basis after a thorough investigation.
The objective of this work was to determine the interference periods of weeds of the bell pepper cultivar ‘Dahra’. Two experiments were conducted during the years 2014/15 (harvest with lower ...rainfall) and 2015/16 (harvest with higher rainfall). The treatments consisted of 11 growing periods of cohabitation and weed control with ‘Dahra’ bell peppers: 14, 28, 42, 56, 70, 84, 98, 112, 126, 140 and 154 days after transplanting (DAT). For the determination of the interference periods, the productivity data were analyze using the Boltzmann sigmoidal regression model. The main weeds were Eleusine indica, Brachiaria plantaginea, Digitaria nuda and Nicandra physaloides for presenting high biomass and relative density. The concomitance of these weeds caused losses of up to 85.22% (2014/15) and 86.2% (2015/16) in the fruit yield. It was found that, respectively, for the years 2014/15 and 2015/16, the period before the interference was 17 and 11 DAT, and the total interference prevention period of 71 and 89 DAT. Considering a tolerance of 5% in reducing bell pepper yield, it is recommended that weed control be performed from 11 to 89 DAT.
RESUMO: Objetivou-se com este trabalho determinar os períodos de interferência de plantas daninhas infestantes do pimentão cultivar Dahra. Dois experimentos foram conduzidos durante os anos 2014/15 (safra com menor precipitação pluviométrica) e 2015/16 (safra com maior precipitação pluviométrica). Os tratamentos consistiram de 11 períodos crescentes de convivência e controle das plantas daninhas com o pimentão Dahra: 14, 28, 42, 56, 70, 84, 98, 112, 126, 140 e 154 dias após o transplantio (DAT). Para a determinação dos períodos de interferência, os dados de produtividade foram analisados utilizando o modelo de regressão sigmoidal de Boltzmann. As principais plantas daninhas foram Eleusine indica, Brachiaria plantaginea, Digitaria nuda e Nicandra physaloides, por apresentarem alta biomassa e densidade relativa. A convivência com as plantas daninhas provocou perdas na produtividade de frutos de 85,22% (2014/15) e 86,2% (2015/16). Constatou-se que, respectivamente, para os anos 2014/15 e 2015/16, o período anterior à interferência foi dos 17 aos 11 DAT, e o período total de prevenção à interferência, dos 71 aos 89 DAT. Considerando uma tolerância de 5% na redução da produtividade do pimentão, recomenda-se que o controle das plantas daninhas seja realizado de 11 a 89 DAT.
PDF
