Effect of the number of daily distributions of solid feed on veal calves' health status, behaviour, and alterations of rumen and abomasa

The research aimed at evaluating the effect of three versus two daily distributions of solid feed on veal calves' health, behaviour, and rumen and abomasal mucosa alterations with the rationale that three distributions might improve calves' health and welfare. The study was carried out in two veal calf farms that provided different amounts of solid feed (farm A 200 kg DM/calf; farm B 150 kg DM/calf) during the fattening in addition to liquid milk-replacer. It involved 342 calves in farm A and 108 calves in farm B. The change from two to three solid feed distributions/day started for half calves/farm after the third month of fattening when farm A was feeding 800 g and farm B 600 g DM/calf/day. Health status, blood haemoglobin, and behaviour were assessed on farm at different times. Calves' carcass weight was recorded and rumens and abomasa were inspected post mortem. Increasing solid feed distributions did not improve calves' health but it reduced non-nutritive oral behaviours (4.8 versus 3.2 ± 0.4% for two and three distributions/day, respectively) by prolonging the time spent eating solid feed. Carcass weight was similar between treatments. Three daily solid feed distributions did not reduce the prevalence of rumen mucosa hyperkeratinisation and abomasal alterations, worsening the frequency of rumen plaques. As the partition of daily dose of solid feed in three distributions is more time and labour consuming, its benefits addressing only the reduction of non-nutritive oral behaviours seem not sufficient to justify the routinely adoption of this practice by veal producers

Low plasma PD-L1 levels, early tumor onset and absence of peritoneal carcinomatosis improve prognosis of women with advanced high-grade serous ovarian cancer

BackgroundThe most common subtype of ovarian cancer (OC) showing immunogenic potential is represented by the high-grade serous ovarian cancer (HGSOC), which is characterized by the presence of tumor-infiltrating immune cells able to modulate immune response. Because several studies showed a close correlation between OC patient's clinical outcome and expression of programmed cell death protein-1 or its ligand (PD-1/PD-L1), the aim of our study was to investigate if plasma levels of immunomodulatory proteins may predict prognosis of advanced HGSOC women.Patients and methodsThrough specific ELISA tests, we analyzed plasma concentrations of PD-L1, PD-1, butyrophilin sub-family 3A/CD277 receptor (BTN3A1), pan-BTN3As, butyrophilin sub-family 2 member A1 (BTN2A1), and B- and T-lymphocyte attenuator (BTLA) in one hundred patients affected by advanced HGSOC, before surgery and therapy. The Kaplan-Meier method was used to generate the survival curves, while univariate and multivariate analysis were performed using Cox proportional hazard regression models.ResultsFor each analyzed circulating biomarker, advanced HGSOC women were discriminated based on long (>= 30 months) versus short progression-free survival (PFS < 30 months). The concentration cut-offs, obtained by receiver operating characteristic (ROC) analysis, allowed to observe that poor clinical outcome and median PFS ranging between 6 and 16 months were associated with higher baseline levels of PD-L1 (> 0.42 ng/mL), PD-1 (> 2.48 ng/mL), BTN3A1 (> 4.75 ng/mL), pan-BTN3As (> 13.06 ng/mL), BTN2A1 (> 5.59 ng/mL) and BTLA (> 2.78 ng/mL). Furthermore, a lower median PFS was associated with peritoneal carcinomatosis, age at diagnosis > 60 years or Body Mass Index (BMI) > 25. A multivariate analysis also suggested that plasma concentrations of PD-L1 <= 0.42 ng/mL (HR: 2.23; 95% CI: 1.34 to 3.73; p = 0.002), age at diagnosis <= 60 years (HR: 1.70; 95% CI: 1.07 to 2.70; p = 0.024) and absence of peritoneal carcinomatosis (HR: 1.87; 95% CI: 1.23 to 2.85; p = 0.003) were significant prognostic marker for a longer PFS in advanced HGSOC patients.ConclusionsThe identification of high-risk HGSOC women could be improved through determination of the plasma PD-L1, PD-1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels

SHARK-NIR, the coronagraphic camera for LBT, moving toward construction

SHARK-NIR is one of the two coronagraphic instruments proposed for the Large Binocular Telescope. Together with SHARK-VIS (performing coronagraphic imaging in the visible domain), it will offer the possibility to do binocular observations combining direct imaging, coronagraphic imaging and coronagraphic low resolution spectroscopy in a wide wavelength domain, going from 0.5{\mu}m to 1.7{\mu}m. Additionally, the contemporary usage of LMIRCam, the coronagraphic LBTI NIR camera, working from K to L band, will extend even more the covered wavelength range. In January 2017 SHARK-NIR underwent a successful final design review, which endorsed the instrument for construction and future implementation at LBT. We report here the final design of the instrument, which foresees two intermediate pupil planes and three focal planes to accomodate a certain number of coronagraphic techniques, selected to maximize the instrument contrast at various distances from the star. Exo-Planets search and characterization has been the science case driving the instrument design, but the SOUL upgrade of the LBT AO will increase the instrument performance in the faint end regime, allowing to do galactic (jets and disks) and extra-galactic (AGN and QSO) science on a relatively wide sample of targets, normally not reachable in other similar facilities.Comment: 8 pages, 6 figures, AO4ELT5 conference proceeding

Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome

About 10–20% of breast/ovarian (BC/OC) cancer patients undergoing germline BRCA1/2 genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline BRCA1/2 VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk BRCA variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlinico “P. Giaccone” of Palermo, were genetically tested for germline BRCA1/2 variants through Next-Generation Sequencing analysis. The mutational screening showed that 639 (73.1%) out of 874 patients were BRCA-w.t., whereas 67 (7.7%) were carriers of germline BRCA1/2 VUSs, and 168 (19.2%) harbored germline BRCA1/2 pathogenic/likely pathogenic variants. Our analysis revealed the presence of 59 different VUSs detected in 67 patients, 46 of which were affected by BC and 21 by OC. Twenty-one (35.6%) out of 59 variants were located on BRCA1 gene, whereas 38 (64.4%) on BRCA2. We detected six alterations in BRCA1 and two in BRCA2 with unclear interpretation of clinical significance. Familial anamnesis of a patient harboring the BRCA1-c.3367G>T suggests for this variant a potential of pathogenicity, therefore it should be carefully investigated. Understanding clinical significance of germline BRCA1/2 VUS could improve, in future, the identification of potentially high-risk variants useful for clinical management of BC or OC patients and family members

Body mass index and baseline platelet count as predictive factors in Merkel cell carcinoma patients treated with avelumab

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the “obesity paradox”, has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking.Patients and methodsThis is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with avelumab as first-line treatment. The study population included the patients treated from February 2019 to October 2022 in an Italian referral center for rare tumors. Clinico-pathological characteristics, BMI, laboratory parameters (NLR and platelet count), and response to avelumab were analyzed from a MCC System database prospectively collected.ResultsThirty-two (32) patients were included. Notably, the presence of pre-treatment BMI ≥ 30 was significantly associated with longer PFS [BMI < 30 Group: median PFS, 4 months (95% CI: 2.5-5.4); BMI ≥ 30 Group: median PFS, not reached; p<0.001)[. Additionally, the median PFS was significantly higher in patients with higher PLT (median PFS: 10 months in the “low PLT” Group (95% CI: 4.9, 16.1) vs 33 months (95% CI: 24.3, 43.2) in the “high PLT” Group (p=0.006). The multivariable Cox regression model confirmed these results.ConclusionTo our knowledge, this is the first study that investigates the predictive role of BMI in MCC patients. Our data were consistent with the clinical observation of improved outcomes in obese patients across other tumor types. Thus, advanced age, a weakened immune system, and the obesity-associated “inflammaging”, are key factors that could impact the cancer immune responses of mMCC patients

Precision and efficiency of a mechanized delivery system of solid feeds for veal calves

To improve animal health and welfare of veal calves, since 1997, the European Union made mandatory the provision of a minimum daily amount (50 to 250 g) of fibrous feed in addition to the milk replacer diet. However more recently, the high costs of milk replacer ingredients have become an economic incentive to increase the amount of fibrous feed provided to the calves as partial substitute of the milk replacer. Solid feed provision has been shown to decrease abnormal behaviours such as oral stereotypes and improving calves rumination and rumen development. Moreover, increasing labour cost and herd sizes of the Italian veal sector have supported a growing interest by the calf producers towards the mechanization of the solid feed delivery. The main purpose of this paper is to show how the implementation of mechanized feeding systems can improve feed intake control, feeding rate and delivery efficiency if compared to the manual delivery of the solid portion of calves diet. Indeed, manual feeding is the most diffused system in veal calves dairy farm but exhibits many disadvantages in terms of distribution homogeneity and labour costs for the livestock farm. The study focuses on the results of an electric self-propelled prototype tested in a veal calves farm, allowing mixing of all solid feed ingredients and control of the weight of the feed delivered to each manger. It is shown how nutritional homogeneity can be improved, reducing deviations by a factor of 4 with respect to manual delivery in the case of crude protein and neutral detergent fiber. Additionally it is shown how single ration quantity variability can be reduced from over 30% in the case of manual delivery to less than 10% in the case of mechanized delivery