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Aortic valve stenosis (AVS) is the most common valvular heart disease in the Western world. Therapy based on apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins, results in AVS regression in experimental models. Nevertheless, apoA-I degradation by proteases might lead to suboptimal efficacy of such therapy. An activatable probe using a quenched fluorescently labeled full-length apoA-I protein was generated to assess apoA-I-degrading protease activity in plasma derived from 44 men and 20 women with severe AVS (age 65.0 ± 10.4 years) as well as from a rabbit model of AVS. In human and rabbit AVS plasma, apoA-I-degrading protease activity was significantly higher than in controls (humans: 0.038 ± 0.009 vs 0.022 ± 0.005 RFU/s, p < 0.0001; rabbits: 0.033 ± 0.016 vs 0.017 ± 0.005 RFU/s, p = 0.041). Through the use of protease inhibitors, we identified metalloproteinases (MMP) as exerting the most potent proteolytic effect on apoA-I in AVS rabbits (67%, p < 0.05 vs control), while the cysteine protease cathepsin S accounted for 54.2% of apoA-I degradation in human plasma (p < 0.05 vs control) with the maximum effect seen in women (68.8%, p < 0.05 vs men). Accordingly, cathepsin S activity correlated significantly with mean transaortic pressure gradient in women (r = 0.5, p = 0.04) but not in men (r = − 0.09, p = 0.60), and was a significant independent predictor of disease severity in women (standardized beta coefficient 0.832, p < 0.001) when tested in a linear regression analysis. ApoA-I proteolysis is increased in AVS. Targeting circulating cathepsin S may lead to new therapies for human aortic valve disease.

Marine mammals and fisheries often target the same resources, which can lead to operational interactions. Potential consequences of operational interaction include entanglements and damaged or reduced catches but also enhanced foraging opportunities, which can attract marine mammals to fishing vessels. Responsible fisheries management therefore requires detailed knowledge of the impact of these interactions. In northern Norway, killer whales Orcinus orca are frequently observed in association with large herring aggregations during the winter. We use a combination of biotelemetry and fisheries data to study if, to what extent and at what distances killer whales are attracted to fishing activity. Twenty-five satellite transmitters were deployed on killer whales at herring overwintering and spawning grounds, often near fishing vessels. Over 50% of the killer whale core areas of high usage overlapped with the fisheries core areas, and individual whales spent up to 34% of their time close to active fishing. We used a 3-state hidden Markov model to assess whether killer whale movements were biased towards fishing activities. Of the overall whale movements, 15% (CI = 11-21%) were biased towards fishing activities, with marked heterogeneity among individuals (0-57%). During periods of active fishing, whale movements were biased towards fishing events 44% (CI = 24-66%) of the time, with individual percentages ranging from 0 to 79%. Whales were more likely to be attracted when they were within 20 km. This information can be used in fishery management to consider potential consequences for fishers and whales.

Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P1) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P1 caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis. Mice were exposed subchronically to Methanosphaera stadtmanae (MSS) in order to induce an hypersensitivity pneumonitis-like disease. MSS exposure induced B-cell-rich TLTs surrounded by S1P1-positive microvessels. Upon MSS rechallenge, the S1P1 agonist RP001 prevented the pulmonary increase of CXCL13, a chief regulator of B-cell recruitment in lymphoid tissues. This was associated with a complete inhibition of MSS rechallenge-induced TLT enlargement and with a 2.3-fold reduction of MSS-specific antibody titers in the lung. Interference with TLT reactivation was associated with a 77% reduction of neutrophil accumulation and with full inhibition of protein-rich leakage in the airways. Thus, an S1P1 agonist hinders TLT enlargement upon antigenic rechallenge and inhibits key pathognomonic features of experimental hypersensitivity pneumonitis.

Currently, only surgical treatment of obesity achieves lasting results on weight loss and the improvement of comorbidities in the event of severe obesity ormassive. But this surgery is not without risk and follow-up multidisciplinary must be organized in the long term with the collaboration of the different care actors.

The immunisation properties of an inactivated bluetongue virus serotype 8 (BTV-8) vaccine were evaluated in sheep and cattle. Five sheep were vaccinated with one dose of vaccine and five cattle were vaccinated with two doses 28 days apart. Six sheep and five cattle served as unvaccinated controls. All animals were subjected to a virulent BTV-8 challenge, and safety and antibody responses were monitored. All control animals developed disease and viraemia, while vaccinated animals were clinically protected and viraemia was completely prevented.

The protective properties of an inactivated bluetongue virus serotype 2 (BTV-2) vaccine were evaluated in sheep. Sheep (two groups of seven), vaccinated with either one or two doses of the vaccine, were monitored for antibody response over one year. All sheep developed high titres of neutralizing antibodies by 35 days after first vaccination and titres were maintained over one year. Control sheep ( n = 7) remained seronegative until challenge. One year after vaccination, all sheep were inoculated with a virulent BTV-2. All controls developed pyrexia, clinical signs and viraemia. In contrast, the sheep vaccinated with one or two doses of inactivated BTV-2 vaccine were protected from clinical disease and viraemia was completely prevented. These data show that a single dose of the BTV-2 vaccine given to sheep induces a strong immunity which confers protection for at least one year.

Background Appendectomy is increasingly performed as a ‘short stay’ or ‘ambulatory’ procedure, yet there is no consensus for selection of patients with acute appendicitis for ambulatory surgery (AS). We aimed to compare characteristics and outcomes of complicated and uncomplicated appendectomies performed in ambulatory vs. conventional settings, and to determine factors associated with unexpected re-consultations and re-hospitalizations. Methods The authors reviewed a consecutive series of 185 laparoscopic appendectomies. Whenever possible, patients were offered AS, defined as ‘discharge on the same working day.’ Multivariable regressions were performed to determine associations of unexpected re-consultations and re-hospitalizations with surgery type (ambulatory or conventional) and patient characteristics (age, gender, obesity, symptoms, appendicolith, perforations, appendix diameter, serologic results, American Society of Anesthesiologists score, and Saint-Antoine score). Results From the initial cohort, 117 patients (63.2%) were eligible for AS, of which 8 had peri- or post-operative contraindications. Therefore, 109 patients (58.9%) were operated by AS, with median length of stay 8.5 h (range, 3.3–20.5). Ambulatory cases had a lower incidence of complications (11.9%) than conventional cases (25.0%) ( p  = 0.029). Uni- and multi-variable regressions revealed that unexpected re-consultations were not significantly associated with any of the pre- or peri-operative variables but that unexpected re-hospitalizations were 4 times more likely for patients with appendicolith (OR, 4.32; p  = 0.04). Conclusions Ambulatory surgery could be considered as a standard procedure for both complicated and uncomplicated acute appendicitis. Appendicolith was found to be an independent risk factor for unexpected re-hospitalization and should therefore trigger closer monitoring.

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P  = 4.94 × 10 –8 ) near the natriuretic peptide receptor 3 gene ( NPR3 ). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P  = 2.95 × 10 –8 ) in interaction with colchicine ( P  = 1.19 × 10 –5 ) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.

Polar bears Ursus maritimus are currently facing rapid environmental changes with loss of sea ice and shifts in their prey distribution. Two distinct ecotypes exist in the Barents Sea, where sea ice is decreasing at the highest rate in the Arctic. Coastal bears remain within the Archipelago of Svalbard year-round, whereas offshore bears follow the marginal ice zone (MIZ). We explored these 2 ecotypes’ habitat use, activity and energy needs as well as seasonal variation within these parameters. During the period from 2011-2018, adult female polar bears were equipped with GPS collars and activity sensors (n = 84); 46 of these were equipped with conductivity switches to record aquatic behaviour. Offshore bears travelled longer distances at a higher speed on land and at sea away from land and had a higher activity rate compared to coastal bears. This translated into higher overall energy expenditure. Offshore bears also undertook more distant and energetically costly trips from land to the MIZ, swimming in open water. Both ecotypes showed similar seasonal patterns of activity and movement consistent with their life history linked to sea ice phenology. Despite higher energy expenditure, the offshore strategy seemed to be as profitable as the coastal one as females had marginally better spring body condition, likely due to their specialized high caloric diet of seals throughout the year. However, both ecotypes are currently experiencing habitat changes. Future studies should aim to predict how rapidly declining sea ice in the Barents Sea may challenge polar bears energetically during the coming decades.