Ruthenium (0) complexes with NHC tetrazolylidene ligands: Synthesis, characterization and reactivity

Here we present two new phenyl-tetrazolylidene carbenes as ligands in non-mesoionic (1,4-substitution pattern) and mesoionic (1,3-substitution pattern) tetrazolylidene-cyclopentadienone ruthenium(0) complexes namely 1 and 2 respectively. The complexes have been obtained in good yield and fully characterized; X-ray structure determination confirmed the binding mode of the ligand for 2. Reactivity studies has been performed in order to shed light on the fact that the phenyl substituent position in the heterocyclic ligand can seriously change complexes behavior and stabilit

Editorial: Biotechnological Uses of Archaeal Proteins

Many industrial/biotechnological processes take place under extreme conditions of temperature, pH, salinity, or pressure which are not suitable for activities of proteins from model eukaryotic or common neutrophilic, mesophilic, and prokaryotic microorganisms. In contrast, Archaea offer a large panel of extremophile organisms that express proteins that are able to remain properly folded and functional under the harshest biophysical conditions

Platelet-Rich Plasma combined with a sterile 3D polylactic acid scaffold for postoperative management of complete hoof wall resection for keratoma in four horses.

Keratoma is a non-malignant horse tumour that grows in the space between the horn of the hoof and the distal phalanx. Keratoma causes lameness in the horse, and surgical excision is the treatment of choice. Four horses underwent removal of a keratoma by complete hoof wall resection. The remaining wound was treated with Platelet-Rich Plasma (PRP) combined with a sterile 3D polylactic acid scaffold. The PRP was applied at 3, 6, 9, 12, 15 and 18 days postoperatively. The surgical site was cleaned with gauzes and swabs soaked in Ringer’s lactate solution before applying PRP and the foot bandage. Healthy granulation tissue developed at 6-21 days postoperatively. The hoof wall defect was completely filled with new hoof wall within 6-8 months after surgery. All horses returned to their previous exercise level and no recurrence of lameness was reported by the owner

Environmental influences on the physiological and behavioural growth responses in salmonids : with reference to the growth-dip phenomenon

Photoperiod manipulations are widely used throughout the Atlantic salmon (Salmo salar) farming industry as a means of producing a product of uniform quality all-year round. However, farmers still remain sceptical over their effectiveness to regulate growth and maturation during the on-growing stage. Furthermore, reports of a characteristic growth-dip following light exposure suggest that light may negatively affect the physiological performance of fish in the short-term. Thus, this thesis investigates the effects of light characteristics (spectral quality, intensity and photoperiod) on growth and maturation of salmonid fish and addresses some of the uncertainties surrounding photoperiod use currently reported within the industry. Rainbow trout (Oncorhynchus mykiss) are seemingly an ideal model species for examining photoperiod effects on growth. Consequently, the application of constant light exposure (LL) at two different intensities (28W and 16W) during two different thermal conditions (summer and winter) was examined on individually tagged fish. Feed intake and growth appeared to be related to the ambient water temperature and did not appear to be affected by intensity or photoperiod, although the onset of constant light did appear to initially affect growth rate. This may indicate that LL has a limiting effect on the growth of trout or that the prevailing water temperature at which light is applied may override the photoperiodic effect. Furthermore, the lack of enhanced growth in trout exposed to LL, unlike that demonstrated for other salmonids, suggest that there may be a species-specific response to environmental variables. Thus, questions regarding photoperiod effects should be limited to the species in question. The main source of variation in results observed under photoperiod manipulations stems from the salmon industry. Atlantic salmon post-smolts were reared in seawater tanks and either maintained under a natural photoperiod (NP) or exposed to a simulated natural photoperiod (SNP), constant light superimposed on the natural light (NPLL) or constant light only (LL). Artificial light onset, irrespective of photoperiod, resulted in an apparent trend for a reduced appetite lasting up to 60 days. Furthermore, the onset of constant light resulted in a significant chronic elevation of plasma cortisol levels and changes to growth and thyroid hormone levels, providing direct evidence that constant light exposure induces stress. In addition, fish exposed to SNP failed to exhibit a stress response despite a low feed intake. However, differences in the plasma melatonin levels during twilight times, as compared to NP, suggest that gradual changes in the natural light intensity throughout the day, particularly around dawn and dusk, may be important for synchronizing daily events. No differences in growth were observed between the NP and NPLL regimes, although fish reared in an enclosed regime (SNP and LL) exhibited a significantly lower weight gain than fish in an open environment (NP and NPLL). This further highlights the impact that the rearing environment has on the growth performances of fish and the need for commercially run trials. Advances in lighting technologies and a greater understanding of how light is transformed through the water column have focussed research on the spectral sensitivity of fish. Therefore the lighting efficiency of novel blue narrow bandwidth LED lighting units through the water column and their effects on growth and maturation performances of salmon reared in commercial production cages were compared against the standard metal halide units currently utilized throughout the industry. LL application, irrespective of intensity or spectrum, reduced the numbers of fish maturing as compared to fish reared under a natural photoperiod. However, this was greatest under the standard metal halide units reflecting a greater light penetration and perception as determined by plasma melatonin levels. The metal halide groups exhibited the greatest relative weight gain over the trial period as compared to control fish. No evidence was observed for a growth-dip under metal halide light, although blue lit treatments exhibited an initial significant reduction in food consumption, suggesting a possible welfare issue. Nevertheless, the prototype blue LED units showed possible potential for commercial application by penetrating the water depth at half the distance of the metal halide units for only one eighth the power and one fifth the brightness. However, further tests of these prototype spectral units are required to examine the potential welfare and physiological growth and reproductive effects. These studies have shown that the efficacy of artificial light regimes is largely dependent upon the effectiveness of the light source through the underwater environment and its perception by fish, providing a sufficient intensity is emitted exceeding the physiological threshold level for the species cultured. Moreover, whilst the onset of artificial light may elicit a stress response and demonstrate a trend for a suppression of appetite for salmon reared in experimental tanks, no compelling evidence for a suppression of appetite or growth was found under normal commercial cage conditions. This suggests that the growth-dip observed within the industry may in part be a combination of a physiological response to the onset of light further exaggerated by the farmer’s perception and altered judgement in feeding. In addition, the results obtained from this study have helped to standardize the use of light regimes within the industry. Nevertheless, further studies are necessary to fully elucidate the underlying mechanisms which may govern growth and maturation in fish following the onset of light exposure.EThOS - Electronic Theses Online ServiceNutreco Aquaculture Research centre/Marine Harvest (Stavenger, Norway)University of StirlingFisheries Society of the British IslesGBUnited Kingdo

Severe pneumonia caused by Legionella pneumophila serogroup 11, Italy.

Legionella pneumophila serogroups (SGs) 1–16 cause pneumonia in humans. Although SG 1 is the serogroup most commonly associated with disease, we report a case of community-acquired legionellosis caused by SG 11

No impact of previous NRTIs resistance in HIV positive patients switched to DTG+2NRTIs under virological control: Time of viral suppression makes the difference

The accumulation of drug-resistance mutations on combined antiretroviral regimens (ART) backbone could affect the virological efficacy of the regimen. Our aim was to assess the impact of previous drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) on the probability of virological failure (VF) in patients, under virological control, who switched to dolutegravir (DTG)+2NRTIs regimens. All HIV-1 positive drug-experienced patients who started a regimen composed by DTG+2NRTIs [abacavir/lamivudine or tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)/emtricitabine (FTC)] in the ARCA collaborative group with HIV-RNA <50 cp/mL were included in the analysis. Patients with a previous VF to integrase inhibitors were excluded. The impact of single and combined NRTIs mutations on the probability of VF (defined as 2 consecutive HIV-RNA >50 copies/mL or one HIV-RNA >1000 copies/mL) was assessed by Kaplan Meier curves. A multivariable Cox regression analysis was constructed to assess factors potentially related to VF. Five hundred and eighty-eight patients were included in the analysis with a median time of viral suppression before the switch of 37 months (IQR 12-78), of whom 148 (25.2%) had at least one previous NRTIs resistance mutation. In the multivariable model no association was observed between NRTIs mutations and VF. Conversely, the duration of viral suppression before switch resulted associated with a lower risk of VF (for 1 month increase, adjusted 0.98, 95%CI 0.96-0.99; p=0.024). Previous NRTIs mutations appeared to have no impact on the risk of VF in patients switched to DTG+2NRTIs, whereas a longer interval on a controlled viremia decreased significantly the risk of VF

Impact of transmitted drug resistance in naïve-patients starting 2 NRTI plus a boosted protease-inhibitor (PI) or integrase-inhibitor (INSTI).

Background The role of transmitted drug resistance (TDR) in predicting outcomes of initial antiretroviral therapy including PI or INSTI has not been fully explored. Methods From the ARCA database we selected adult naïve HIV-1 infected patients starting first-line 3-drugs therapy including INSTI or PI, from 1/2008 to 6/2016, with baseline resistance genotype and at least 1 HIV-1 RNA during follow up. TDR was defined as the detection of at least one mutation among those included in the WHO-recommended SDRM list (Bennett 2009). The primary endopoints were: virological failure (VF, defined as an HIV-RNA, VL, > 200 copies/ml after week 24) and treatment failure (TF, defined as VF or treatment change for any reason). Survival analysis was used to investigate predictors of TF and VF. Results 1147 pts were analyzed: 1031 (89.9%) treated with PI and 116 (10.1%) with INSTI. Baseline characteristics are shown in table. In the PI-group baseline VL was higher while CD4+ cells count was lower than in INSTI. Overall TDR were 4.7% for NRTI, 4.4% NNRTI, 1.5% PI without significant differences between groups. During a median observation time of 57 wks (IQR 26-107) TF occurred in 771 treatments in PI-group, with an estimated probability at 48 wks of 36% (CI 34.5-37.5) and in 46 in INSTI-group with an estimated probability at 48 wks of 31% (26.2-35.8); during a median observation time of 55 wks (26-107) VF occurred in 161 treatments in PI-group, with an estimated probability at 48 wks of 12% (10.8-13.1) and in 11 in INSTI-group with an estimated probability at 48 wks of 12% (8.5-15.5). After adjusting for gender, nationality, TDF/FTC use and viral subtype, independent predictor of VF was AZT/3TC use (vs other backbones HR 3.8, CI 95% 2.2-6.3, p<0.001); adjusting for nationality and viral subtype, independent predictors of TF were geographic area (Southern vs Northern Italy, HR 0.8, 0.6-0.9, p=0.04), baseline VL (+ 1 log10 HR 1.1, 1.0-1.2, p=0.03) and AZT/3TC (versus other backbones HR 2.1, 1.5-2.8, p=<0.001). Third drug class was not associated with VF or TF. In the INSTI-group, but not in the PI-group, the presence of any NRTI TDR was predictor of VF (HR 7.1, 1.8-28.2, p=0.005) after adjusting for nadir CD4 cells count and TF (HR 2.7, 1.1-7.0, p=0.03). Among patients in the INSTI-group with VF, 3 presented NRTI TDR (2 M41L and 1 M184V). In the PI-group, adjusting for gender, nationality, geographic area, viral subtype, TDF/FTC use, baseline and nadir CD4 cells count, independent predictor of VF was AZT/3TC use (HR 3.4, 1.8-6.2, p<0.001); adjusting for nationality and viral subtype, independent predictor of TF was AZT/3TC use (vs other backbones HR 2.3, 1.7-3.1, p<0.001). Conclusions PI and INSTI based first-line regimens show high efficacy in the real practice; despite the low incidence of TDR, our data support the need of pre-treatment genotyping to optimize therapy in patients starting INSTI-therapy. Further studies are required to confirm our suggestions

Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV-2 infection: Retrospective cohort study

Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching. Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation

A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

<p>Abstract</p> <p>Background</p> <p>HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.</p> <p>Methods</p> <p>We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90^thday after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.</p> <p>Results</p> <p>The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.</p> <p>Conclusions</p> <p>GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.</p