Alkaline phosphatase survey in pecorino siciliano PDO cheese

The determination of alkaline phosphatase (ALP) in cheeses has become an official method for controlling cheeses with a protected designation of origin (PDO), all of which use raw milk. PDO cheeses, characterized by high craftsmanship, usually have an uneven quality. However, for these cheeses, it is necessary to establish ALP values so that they can be defined as a raw milk product. In this study, a dataset with Pecorino Siciliano PDO samples was analyzed to determine ALP both at the core and under the rind. The results showed that there was no significant difference between the different zones in Pecorino cheese. A second dataset of 100 pecorino cheese samples determined that ALP was only at the core of the cheese. Moreover, there was a statistically significant difference between the ALP values of cheeses produced with raw milk and those produced with pasteurized milk. Furthermore, according to the temperatures, a wide variability of ALP values was observed in the Pecorino Siciliano PDO samples from the core of the cheeses. This was a result of several under scotta whey cooking methodologies adopted by cheesemakers, which do not permit a clear range. Therefore, further investigation is desirable

Bone fracture as a novel immune-related adverse event with immune checkpoint inhibitors: Case series and large-scale pharmacovigilance analysis

Although immune checkpoint inhibitors (ICIs) are associated with different immune-related adverse events (irAEs), the potential effect on the skeleton is poorly defined albeit biologically plausible and assessable through pharmacovigilance. We described a case series of patients experiencing skeletal fractures while on ICIs at the National Cancer Institute of Milan. To better characterize the clinical features of skeletal irAEs reported with ICIs, we queried the FDA Adverse Event Reporting System (FAERS) and performed disproportionality analysis by means of reporting odds ratios (RORs), deemed significant by a lower limit of the 95% confidence interval (LL95% CI) > 1. Bone AEs emerging as significant were scrutinized in terms of demographic and clinical data, including concomitant irAEs or drugs affecting bone resorption or causing bone damage. Four patients with skeletal events while on ICIs were included in our case series, of which three exhibited vertebral fractures. In FAERS, 650 patients with bone and joint injuries and treated with ICIs were retrieved, accounting for 822 drug-event pairs. Statistically significant ROR was found for eight, two and one bone AEs respectively with PD-1, PD-L1 and CTLA-4 inhibitors, being pathological fracture (N = 46; ROR = 3.17; LL95%CI = 2.37), spinal compression fracture (42; 2.51; 1.91), and femoral neck fracture (26; 2.38; 1.62) the most common. Concomitant irAEs or drugs affecting bone metabolism were poorly reported. The increased reporting of serious vertebral fractures in patients without concomitant irAEs and no apparent preexisting risk factors could suggest a possible cause-effect relationship and calls for close clinical monitoring and implementation of dedicated guidelines

In-depth investigation of the safety of wooden shelves used for traditional cheese ripening

The main goal of this research was to characterize the bacterial diversity of the wooden boards used for aging traditional Sicilian cheeses and to evaluate whether pathogenic bacteria are associated with these surfaces. Eighteen cheese dairy factories producing three traditional cheese typologies (PDO Pecorino Siciliano, PDO Piacentinu Ennese, and Caciocavallo Palermitano) were selected within the region of Sicily. The wooden shelf surfaces were sampled by a destructive method to detach wood splinters as well as by a nondestructive brushing to collect microbial cells. Scanning electron microscopy showed the presence of almost continuous bacterial formations on the majority of the shelves analyzed. Yeasts and fungal hyphae were also visualized, indicating the complexity of the plank communities. The amplicon library of the 16S rRNA gene V3-V4 region was paired-end sequenced using the Illumina MiSeq system, allowing the identification of 14 phyla, 32 classes, 52 orders, 93 families, and 137 genera. Staphylococcus equorum was identified from all wooden surfaces, with a maximum abundance of 64.75%. Among cheese-surface-ripening bacteria, Brevibacterium and Corynebacterium were detected in almost all samples. Several halophilic (Halomonas, Tetragenococcus halophilus, Chromohalobacter, Salimicrobium, Marinococcus, Salegentibacter, Haererehalobacter, Marinobacter, and Idiomarinaceae) and moderately halophilic (Salinicoccus, Psychrobacter, and Salinisphaera) bacteria were frequently identified. Lactic acid bacteria (LAB) were present at low percentages in the genera Leuconostoc, Lactococcus, Lactobacillus, Pediococcus, and Streptococcus. The levels of viable microorganisms on the wooden shelves ranged between 2.4 and 7.8 log CFU/cm2. In some cases, LAB were counted at very high levels (8.2 log CFU/cm2). Members of the Enterobacteriaceae family were detected in a viable state for only six samples. Coagulase-positive staphylococci, Salmonella spp., and Listeria monocytogenes were not detected. Seventy-five strains belonged to the genera Leuconostoc, Lactococcus, Pediococcus, Enterococcus, Lactobacillus, and Weissella. IMPORTANCE This study provides evidence for the lack of pathogenic bacteria on the wooden shelves used to ripen internal bacterially ripened semihard and hard cheeses produced in Sicily. These three cheeses are not inoculated on their surfaces, and surface ripening is not considered to occur or, at least, does not occur at the same extent as surface-inoculated smear cheeses. Several bacterial groups identified from the wooden shelves are typically associated with smear cheeses, strongly suggesting that PDO Pecorino Siciliano, PDO Piacentinu Ennese, and Caciocavallo Palermitano cheese rind contributes to their final organoleptic profiles

Effect of photoperiod on follicular IGF-1 and oocyte quality independently of metabolic status in buffalo heifers

The aim of this study was to determine whether buffalo heifers maintained at a constant live weight (LW) and body condition score (BCS) by a restricted diet show changes in reproductive function in response to changes in day length. Heifers were fed a low energy diet (86% daily intake recommended for the species) throughout the study, which involved an 8-week period of decreasing day length and a 7-week period of increasing day length. Weekly, LW, BCS and ovarian follicular/oocyte population were assessed. Blood and follicular fluid samples were taken at the time of ovum pick-up for hormone analyses and at 30-day intervals to measure metabolic substrates. Buffalo heifers maintained LW and BCS throughout the study and blood concentrations of the main metabolic hormones, such as GH, insulin, IGF-1 and thyroid hormones were not influenced by photoperiod. Likewise, there were no differences in metabolic substrates such as glucose, NEFA, triglycerides and HDL cholesterol, suggesting that the metabolic condition remained essentially the same. During increasing day length periods, the number of total follicles (8.4 ± 0.5 vs. 11.9 ± 0.6; p < .01), cumulus-oocyte complexes (2.2 ± 0.3 vs 4.3 ± 0.5; p < .01) and superior quality Grade A + B COCs (0.2 ± 0.1 vs 1.1 ± 0.2; p < .01) decreased. These features were associated to reduced oestradiol levels both in plasma (3.9 ± 0.4 vs 9.2 ± 0.5 pg/mL; p < .01) and follicular fluid (49.7 ± 12.9 vs. 109.1 ± 25.8 ng/mL; p = .05), as well as to reduced intrafollicular IGF-1 levels (45.5 ± 4.0 vs. 58.5 ± 3.9 ng/mL; p < .05). These findings suggest that the ovarian function in buffalo heifers is influenced by photoperiod independent of nutritional and metabolic status.Highlights Metabolic profile, LW and BCS do not change in buffalo heifers on a restricted diet Photoperiod affects ovarian function in heifers regardless of metabolic status Follicular and oocyte population decrease in increasing day length periods Oestradiol and IGF-1 levels in follicular fluid are affected by photoperio

Fishmeal replacement with hermetia illucens meal in aquafeeds: Effects on zebrafish growth performances, intestinal morphometry, and enzymology

Fishmeal (FM) is still the most important protein source in aquafeeds. However, due to the reduction of wild fish stocks used for FM production, its manufacturing it is now unsustainable. Insect meal represents a valid alternative to FM, due to the low carbon footprint of its production and its high nutritional value. The aim of this study was to investigate the potentials of replacing FM with black soldier fly (Hermetia illucens) meal (HIM) in aquafeeds, using zebrafish as the animal model. Four diets were formulated with increasing HIM/FM replacement rate (the control diet contained 20% FM). Mortality rates, growth performances, and feed consumptions were measured, and fish intestine samples were collected for histological and enzymatic analysis. After 49 days, all groups almost tripled their initial body weight (cumulative body weight gain ranged between 143.9 and 155.2 mg), and no statistically significant differences among treatments were observed in relation to growth performances and histological traits. Contrarily, trypsin, alkaline phosphatases, and alpha amylase–glucoamylase activities were significantly reduced when the FM replacement rate was increased. In conclusion, HIM may represent an alternative to FM, since no adverse effects were observed when it was included up to 20% in the zebrafish diet, even when replacing 100% of the FM

Nivolumab versus investigator&apos;s choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck : efficacy and safety in CheckMate 141 by age

Objectives: Many patients with squamous cell carcinoma of the head and neck (SCCHN) are 6565 years old; comorbidities and other age-related factors may affect their ability to tolerate traditional chemotherapy. Nivolumab is the only immunotherapy to significantly improve overall survival (OS) versus investigator's choice (IC) of single-agent chemotherapy at primary analysis in a phase 3 trial (CheckMate 141) in patients with recurrent/metastatic SCCHN post-platinum therapy. In this post hoc analysis, we report efficacy and safety by age. Patients and methods: Eligible patients were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks (n = 240) or IC (methotrexate, docetaxel, or cetuximab n = 121). The primary endpoint of the trial was OS. For this analysis, outcomes were analyzed by age &lt; 65 and 6565 years. The data cut-off date was September 2017 (minimum follow-up 24.2 months). Results: At baseline, 68 patients (28.3%) receiving nivolumab and 45 patients (37.2%) receiving IC were 6565 years. Baseline characteristics were generally similar across age groups. OS and tumor response benefits with nivolumab versus IC were maintained regardless of age. The 30-month OS rates of 11.2% (&lt;65 years) and 13.0% ( 6565 years) with nivolumab were more than tripled versus corresponding IC rates of 1.4% and 3.3%, respectively. The nivolumab arm had a lower rate of treatment-related adverse events versus IC regardless of age, consistent with the overall patient population. Conclusion: In CheckMate 141, nivolumab resulted in a higher survival versus IC in patients &lt;65 and 6565 years, with a manageable safety profile in both age groups. ClinicalTrials.gov: NCT02105636

The Quality of Five Natural, Historical Italian Cheeses Produced in Different Months: Gross Composition, Fat-Soluble Vitamins, Fatty Acids, Total Phenols, Antioxidant Capacity, and Health Index

Five natural historic cheeses of Southern Italy were investigated\u2014Caciocavallo Palermitano (CP), Casizolu del Montiferru (CdM), Vastedda della Valle del Bel\uecce (VVB), Pecorino Siciliano (PS), and Caprino Nicastrese (CN)\u2014which are produced with raw milk and with traditional techniques and tools, from autochthonous breeds reared under an extensive system. The effects of the month of production on gross composition, MUFA, PUFA, PUFA-\u3c96, PUFA-\u3c93, \u3b1-tocopherol, retinol, cholesterol, TPC, TEAC, and GHIC were evaluated. In CP, CLA, TPC, and GHIC were higher in April than in February. CdM showed higher values in terms of fat, saturated fatty acids, PUFA-\u3c93, \u3b1-tocopherol, TEAC, and GHIC in May than in February and September, while low values in terms of protein, moisture, and CLA were found. In VVB, MUFA, PUFA-\u3c96, and \u3b1-tocopherol increased in June compared with April; conversely, protein, FRAP, and TEAC were higher in April. In PS, protein, CLA, PUFA, PUFA-\u3c93, \u3b1-tocopherol, and GHIC increased in May compared with January; on the contrary, moisture, NaCl, and TEAC showed high values in January. CN showed higher values in terms of PUFA, PUFA-\u3c96, PUFA-\u3c93, TPC, TEAC, and GHIC in April and June compared with January. It is shown that each cheese is unique and closely linked to the production area. Cheeses produced in the spring months showed a high nutritional quality due to the greatest presence of healthy compounds originating from an extensive feeding system. For the purposes of raising awareness of five historical cheeses of Southern Italy that are less known by consumers, and of restoring dignity to the breeders and producers of these cheeses, we studied their quality in terms of chemical composition, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), conjugated linoleic acid (CLA), PUFA-\u3c96, PUFA-\u3c93, \u3b1-tocopherol, retinol, cholesterol, polyphenol content (TPC), total antioxidant capacity (FRAP and TEAC), and health index (GHIC). Two stretched-curd bovine cheeses, Caciocavallo Palermitano (CP) and Casizolu del Montiferru (CdM), two ovine cheeses, Vastedda della Valle del Bel\uecce (VVB) and Pecorino Siciliano (PS), and one caprine cheese, Caprino Nicastrese (CN), were evaluated. These cheeses are produced in different months, with raw milk from animals reared in an extensive feeding system. In April, the CP cheese showed high values for CLA, TPC, and GHIC, while the CN cheese exhibited high PUFA, PUFA-\u3c96, PUFA-\u3c93, TEAC, and GHIC. In May, the CdM cheese exhibited high content of fat, saturated fatty acids, PUFA-\u3c93, \u3b1-tocopherol, TEAC, and GHIC, while the PS cheese showed high values of protein, CLA, PUFA, PUFA-\u3c93, \u3b1-tocopherol, and GHIC. These measured parameters characterize and distinguish each cheese due to links with numerous factors: Species, breed, feeding system, pasture biodiversity, climate, production technology, traditional tools, and ripening type. It is highlighted that, in general, the highest nutritional quality, linked to the highest presence of healthy compounds, originates from the pasture of cheese production in the spring

Smartphone-derived keystroke dynamics are sensitive to relevant changes in multiple sclerosis

BACKGROUND: To investigate smartphone keystroke dynamics (KD), derived from regular typing, on sensitivity to relevant change in disease activity, fatigue, and clinical disability in multiple sclerosis (MS). METHODS: Preplanned interim analysis of a cohort study with 102 MS patients assessed at baseline and 3-month follow-up for gadolinium-enhancing lesions on MRI, relapses, fatigue and clinical disability outcomes. Keyboard interactions were unobtrusively collected during typing using the Neurokeys App. From these interactions 15 keystroke features were derived and aggregated using 16 summary and time series statistics. Responsiveness of KD to clinical anchor-based change was assessed by calculating the area under the receiver operating characteristic curve (AUC). The optimal cut-point was used to determine the minimal clinically important difference (MCID) and compared to the smallest real change (SRC). Commonly used clinical measures were analyzed for comparison. RESULTS: 94 patients completed the follow-up. The five best performing keystroke features had AUC-values ranging from 0.72 to 0.78 for change in gadolinium-enhancing lesions, 0.67-0.70 for the Checklist Individual Strength Fatigue subscale, 0.66-0.79 for the Expanded Disability Status Scale, 0.69-0.73 for the Ambulation Functional System, and 0.72-0.75 for Arm function in MS Questionnaire. The MCID of these features exceeded the SRC on group level. KD had higher AUC-values than comparative clinical measures for the study outcomes, aside from ambulatory function. CONCLUSIONS: KD demonstrated good responsiveness to changes in disease activity, fatigue, and clinical disability in MS, and detected important change beyond measurement error on group level. Responsiveness of KD was better than commonly used clinical measures

Minor-but-Complex Liver Resection: An Alternative to Major Resections for Colorectal Liver Metastases Involving the Hepato-Caval Confluence

Major hepatectomy (MH) is often considered the only possible approach for colorectal liver metastasis (CRLM) at the hepato-caval confluence (CC), but it is associated with high morbidity and mortality. With the aim to reduce MH, we developed the "minor-but-complex" (MbC) technique, which consists in the resection of less than 3 adjacent liver segments with exposure of the CC and preservation of hepatic outflow until spontaneous maturation of peripheral intrahepatic shunts between main hepatic veins. We have evaluated applicability and outcome of MbC resections for the treatment of CRLM involving the CC. In this retrospective cohort study, all consecutive liver resections (LR) performed for CRLM located in segments 1, 7, 8, or 4a were classified as MINOR - removal of bC - removal of = 3 adjacent segments. The rate of avoided MH was obtained by the difference between the rate of potentially MH (PMH) plus potentially inoperable cases and the rate of the MH performed. Taking into account that postoperative mortality is mainly related to the amount of resected liver, MbC was compared with minor resections for safety, complexity, and outcome. Of the 59 LR analyzed, 29 (49.1%) were deemed PMH and 4 (6.8%) potentially inoperable. Eventually, MH was performed only in 8 (13.5%) with a decrease rate of 42.4%. Minor LR was performed in 23 (39.0%) and MbC LR in 28 (47.5%) patients. Among MbC cases, 32.1% had previous liver treatments, 39.3% required vascular reconstruction (no reconstructed vessel thrombosis occurred before maturation of peripheral intrahepatic shunts between main hepatic veins), and 7.1% had grade IIIb-IV complications, their median hospital stay was 9 days and 90-day mortality was 0%. After a median follow-up of 22.2 months, oncological results were comparable with those of minor resections. MbC hepatectomy lowers the need for MH and allows for the resection of potentially inoperable patients without negative impact on safety and survival