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Numidian quartz-rich sandstones collected from four different reconstructed sections along the Apennine chain of Southern Italy, have been studied for their textural, petrographic and geochemical characteristics to verify their potential industrial use. Sampling was carried out along a NW-SE transect: Monteverde and Aquilonia sections at NW (Campania Region) and Valsinni and Rotondella ones at SE (Lucania Region). The sandstones from NW successions are subarkoses with subordinate sublitharenites. High compositional maturity is shown by these sandstones containing high SiO2 values (93wt% in average) and lowest amounts of CaO (0.08 wt%), MgO (0.1wt%), Fe2O3 (0.9 wt%) due to the absence of carbonate components (cement and lithics) and scarce presence of clay-ferruginous cement. The sandstones from SE successions show lower contents of SiO2 (87 wt% in average) and relatively higher contents of CaO (up to 7.4 wt%), MgO (up to 1.9 wt%) and Fe2O3 (up to 4.6 wt%) as compared to the previous ones, connected to the presence of calcite and clay-ferruginous cements; these can be classified as Fe-sands with subordinate sublitharenites. The sandstones from NW area show a better potential vocation to be used in the glass industry. However, the coloring elements contents are too high for clear or optical glass production. They are it is suitable as raw material for colored glass, insulating fibres, foundry molds or air Crete. With the aim of assessing the possible improvement of chemical characters, four granulometric fractions (A< 63 μm, B 63-125 μm, C 125-250 μm and D >250μm) were analyzed considering four samples from NW successions. Based on chemical composition, C and D fractions from Aquilonia area, are the most suitable for a coloured glass, while fractions A (

Peritoneal carcinomatosis (PC) is defined as a metastatic involvement of the peritoneum by several other primary sites and it is characterized by a marked worsening of prognosis, with limited treatment opportunities. Subsequently, PC should be ruled out before any invasive treatment is administered. A new through-the-needle micro-biopsy forceps (MF) was recently introduced that permits micro-histology cores. In this case series, we evaluated the feasibility of MF in the assessment of PC to complete patient diagnostic work-ups. Five consecutive patients referred for endoscopic ultrasound staging were sampled using MF. Sampling was feasible in all patients with a technical success of 100%. No adverse events were reported in any cases. This technique was feasible and safe with a technical success rate of 100%. It permitted sampling of peritoneal irregularity, obtained high-quality tissue fragments in all cases, and enabled an additional assessment, i.e., immunohistochemical staining.

SUMMARYCachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirmed that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of different mouse models and cachectic cancer patients. Testing NAD+ repletion therapy in cachectic mice revealed that NAD+ precursor, vitamin B3 niacin, efficiently corrected tissue NAD+ levels, improved mitochondrial metabolism and ameliorated cancer- and chemotherapy-induced cachexia. To examine NAD+ metabolism in a clinical setting, we showed that the low expression of NRK2 in cancer patients correlated with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose a novel therapy target, NAD+ metabolism, for cachectic cancer patients.

Study question We aimed to verify whether endometriosis patients who succeeded in achieving a live birth through IVF were epigenetically younger than those who did not. Summary answer Applying peripheral blood epigenetic clock, endometriosis women who delivered a baby after assisted reproductive technology (ART) procedures were epigenetically younger than those who did not. What is known already The revolution of “epigenetic clocks”, based on DNA methylation, has ushered in a new era. Epigenetic clocks reflect the possible gap between chronological and biological age. They have recently gained attention also in the reproductive field, since epigenetic mechanisms have been suggested to influence fertility. Moreover, endometriosis progression has been linked to epigenetic factors and the genetic/epigenetic theory has been suggested as a unification theory for its pathogenesis. Study design, size, duration This is a secondary analysis of an observational cohort study, set at the Infertility Unit where we work. In the original study, we prospectively recruited women aged 37-39 years scheduled for an ART procedure between January 2017 and December 2018. For the present study, we considered only women with endometriosis and divided them into two groups: those who delivered and those who did not. Participants/materials, setting, methods Recruited patients did not suffer of relevant systemic diseases, had normal weight and serum FSH levels, and their male partners were not severely infertile. Before the beginning of the IVF cycle, blood samples were collected in EDTA-containing tubes and stored. After DNA extraction, epigenetic age was calculated considering the methylation pattern of 5 CpG sites as reported by Zbieć-Piekarska in 2018. The methylation pattern at these sites were compared between the two groups. Main results and the role of chance Thirty-eight women were enrolled. The cause of infertility was only endometriosis in 33 women or mixed with a concomitant mild male factor in 5 couples. Overall, 12 women (32% of our cohort) obtained a live birth. Women who had a live birth were characterized by higher antral follicular count compared to those who did not with a median value of 10 [6 – 14] and 13 [8-20] respectively (p Limitations, reasons for caution This is a secondary analysis of a cohort study designed for infertility in general, the sample size was limited, and we included only women aged 37-39 years: confirmation in larger studies with broader selection criteria and specifically designed for endometriosis is warranted. Moreover, other epigenetic clocks could have been considered. Wider implications of the findings Our study highlighted the relevance of epigenetics in endometriosis-related infertility. Epigenetic clocks could predict IVF success in affected women. Moreover, a deeper comprehension of these epigenetic mechanisms could lead to interventions aimed at reversing their effects, including modification of such lifestyle factors or hormonal medical treatments. Trial registration number not applicable

Twenty-one sandstone samples belonging to the intermediate part of Gorgoglione Flysch (GF) dated Middle-Miocene, cropping out in the Southern Apennines (Italy), have been studied to highlight the detritus provenance. Petrographic and chemical composition indicates that the successions consist of feldspatho-quartzose and litho-feldspatho-quartzose arenites interbedded with pelitic and calciclastic layers and reveals a provenance from a basement formed by low- to medium-grade metamorphic rocks with abundant granitoids covered by sedimentary rocks in which a volcanic component was also present. In the Mediterranean area, basements with these characteristics are widespread both in western and southwestern domains. The supply provenance of Gorgoglione Flysch has been better detailed utilizing U–Pb detrital zircon ages recording the geological history of the source rocks. Fifty-eight crystals from six samples of coarse- and fine-grained sandstones have been analysed using the U–Pb isotopic systematic (LA-ICP-MS). They produce 70 concordant zircon ages forming three defined clusters at 672 ± 28 Ma, 458 ± 9 Ma and 297 ± 8 Ma, and four zircon ages corresponding to 24 ± 1 Ma. An evaluation of the entire collected data suggests that the provenance area is better identified in northwestern sectors of the Mediterranean area in which the Sardinia–Corsica (pro-part) block plays a fundamental role.

Background: It is a well-known fact that the information obtained from a survey can be used in a healthcare organizational analysis; however, it is very difficult to compare the different results found in the literature to each other, even through the use of metanalysis, as the methodology is often not consistent. Methods: Data from a survey analyzing the organizational and managerial responses adopted in pathology-specific clinical pathways (CPs) during the first two waves of the COVID-19 pandemic were used for constructing a decisional matrix, a tool called SPRIS system, consisting of four different sheets. The first sheet reports the results of the survey and, using a streetlight color system, identifies strengths and weaknesses; the second one, by assigning a priority score, establishes the priority of intervention on each of the strengths and weaknesses identified; the third sheet reports the subjective items of the questionnaire in order to identify threats and opportunities and their probability of happening; in the last sheet, a SWOT Analysis is used to calculate the performance index of the whole organization. Results: The SPRIS system, applied to data concerning the adaptation of four CPs to the COVID-19 pandemic, showed that, whereas all the CPs had a good performance index, some concerns remained unsolved and need be addressed. Conclusions: The SPRIS system showed to be an easily constructed tool that is able to give an overview of the organization analyzed by the survey and to produce an index that can be used in a direct quality comparison between different services or organizations.

In the present study, we unveil the real significance of mylonitic reworking of the polymetamorphic crystalline basement in the Serre Massif of Calabria (Southern Italy). We use a multidisciplinary approach to comprehend the structural, microstructural and petrologic changes that occurred along a, so far, not much considered shear zone affecting the Variscan lower crustal rocks. It was never before studied in detail, although some late Cretaceous ages were reported for these mylonites, suggesting that this shear zone is of prime importance. Our observations reveal now that the formation of the new structural fabric within the shear zone was accompanied by changes in mineral assemblages, in a dominant compressive tectonic regime. During this tectono-metamorphic event, high-P mylonitic mineral assemblages were stabilized, consisting of chloritoid, kyanite, staurolite, garnet and paragonite, whereas plagioclase became unstable. Average peak P–T conditions of 1.26–1.1 GPa and 572–626 °C were obtained using THERMOCALC software. These data question (i) that the Serre Massif represents an undisturbed continuous section of the Variscan crust, as generally suggested in the literature, and (ii) highlight the role of (eo-)Alpine high-P tectonics in the Serre Massif, recorded within mylonite zones, where the Variscan basement was completely rejuvenated.

Rapid tumor growth requires elevated biosynthetic activity, supported by metabolic rewiring occurring both intrinsically in cancer cells and extrinsically in the cancer host. The Warburg effect is one such example, burning glucose to produce a continuous flux of biomass substrates in cancer cells at the cost of energy wasting metabolic cycles in the host to maintain stable glycemia. Amino acid (AA) metabolism is profoundly altered in cancer cells, which use AAs for energy production and for supporting cell proliferation. The peculiarities in cancer AA metabolism allow the identification of specific vulnerabilities as targets of anti-cancer treatments. In the current review, specific approaches targeting AAs in terms of either deprivation or supplementation are discussed. Although based on opposed strategies, both show, in vitro and in vivo, positive effects. Any AA-targeted intervention will inevitably impact the cancer host, who frequently already has cachexia. Cancer cachexia is a wasting syndrome, also due to malnutrition, that compromises the effectiveness of anti-cancer drugs and eventually causes the patient’s death. AA deprivation may exacerbate malnutrition and cachexia, while AA supplementation may improve the nutritional status, counteract cachexia, and predispose the patient to a more effective anti-cancer treatment. Here is provided an attempt to describe the AA-based therapeutic approaches that integrate currently distant points of view on cancer-centered and host-centered research, providing a glimpse of several potential investigations that approach cachexia as a unique cancer disease.

PURPOSE: To assess racial/ethnic and socioeconomic disparities in the difference between atherosclerotic vascular disease prevalence measured by a multi-task convolutional neural network (CNN) deep learning model using frontal chest radiographs (CXRs) and the prevalence reflected by administrative hierarchical condition categories (HCC) codes, in two cohorts of patients with coronavirus disease 2019 (COVID-19). METHODS: A CNN model, previously published, was trained to predict atherosclerotic disease from ambulatory frontal CXRs. The model was then validated on two cohorts of COVID-19 patients: 814 ambulatory patients from a suburban location (presenting 3/14/20 to 10/24/20, the internal ambulatory cohort) and 485 hospitalized patients from an inner-city location (hospitalized 3/14/2020 and 8/12/2020, the external hospitalized cohort). The CNN model predictions were validated against electronic health record (EHR) administrative codes in both cohorts and assessed using the area under the receiver operating characteristic (ROC) curves (AUCs). The CXRs from the ambulatory cohort were also reviewed by two board-certified radiologists and compared to the CNN-predicted values for the same cohort to produce an ROC and AUC. The atherosclerosis diagnosis discrepancy, Δ(vasc), refers to the difference between the predicted value and presence or absence of the vascular disease ICD10 code, was calculated. Linear regression determined the association of Δ(vasc) with the covariates of age, sex, race/ethnicity, language preference and social deprivation index (SDI). Logistic regression was used to look for an association between the presence of any HCC codes with Δ(vasc) and other covariates. RESULTS: The CNN prediction for vascular disease from frontal CXRs in the ambulatory cohort had an AUC of 0.85 (95% confidence interval (CI) = 0.82–0.89) and in the hospitalized cohort had an AUC of 0.69 (95% CI = 0.64–0.75) against the EHR data. In the ambulatory cohort, the consensus radiologists’ reading had an AUC of 0.89 (95% CI = 0.86–0.92) relative to the CNN. Multivariate linear regression of Δ(vasc) in the ambulatory cohort demonstrated a significant negative association with non-English language preference (β = −0.083, P < 0.05) and Black or Hispanic race/ethnicity (β = −0.048, P < 0.05) and a positive association with age (β = 0.005, P < 0.001) and sex (β = 0.044, P < 0.05). For the hospitalized cohort, age was also significant (β = 0.003, P < 0.01), as was SDI (β = 0.002, P < 0.05). The Δ(vasc) variable (odds ratio (OR) = 0.34), Black or Hispanic race/ethnicity (OR= 1.58), non-English language preference (OR = 1.74) and site (OR = 0.22) were independent predictors of having one or more HCC codes (all P < 0.01) in the combined patient cohort. CONCLUSIONS: A CNN model was predictive of aortic atherosclerosis in two cohorts (one ambulatory and one hospitalized) with COVID-19. The discrepancy between the CNN model and the administrative code, Δ(vasc), was associated with language preference in the ambulatory cohort; in the hospitalized cohort, this discrepancy was associated with SDI. The absence of administrative code(s) was associated with Δ(vasc) in the combined cohorts, suggesting that Δ(vasc) is an independent predictor of health disparities. This may suggest that biomarkers extracted from routine imaging studies and compared with EHR data could play a role in enhancing value-based healthcare for traditionally underserved or disadvantaged patients where barriers to care exist.

KRIT1 loss-of-function mutations underlie the pathogenesis of Cerebral Cavernous Malformation (CCM), a major vascular disease affecting the central nervous system (CNS). However, KRIT1 is also expressed outside the CNS and modulates key regulators of metabolic and oxy-inflammatory pathways, including the master transcription factor FoxO1, suggesting a widespread functional significance. Herein, we show that the KRIT1/FoxO1 axis is implicated in liver metabolic functions and antioxidative/antiglycative defenses. Indeed, by performing comparative studies in KRIT1 heterozygous (KRIT1+/−) and wild-type mice, we found that KRIT1 haploinsufficiency resulted in FoxO1 expression/activity downregulation in the liver, and affected hepatic FoxO1-dependent signaling pathways, which are markers of major metabolic processes, including gluconeogenesis, glycolysis, mitochondrial respiration, and glycogen synthesis. Moreover, it caused sustained activation of the master antioxidant transcription factor Nrf2, hepatic accumulation of advanced glycation end-products (AGEs), and abnormal expression/activity of AGE receptors and detoxifying systems. Furthermore, it was associated with an impairment of food intake, systemic glucose disposal, and plasma levels of insulin. Specific molecular alterations detected in the liver of KRIT1+/− mice were also confirmed in KRIT1 knockout cells. Overall, our findings demonstrated, for the first time, that KRIT1 haploinsufficiency affects glucose homeostasis and liver metabolic and antioxidative/antiglycative functions, thus inspiring future basic and translational studies.

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) of solid pancreatic tumors shows optimal specificity despite fair sensitivity, with an overall suboptimal diagnostic yield. We aim to quantify the adequacy and accuracy of EUS-TA and assess predictive factors for success, focusing on the presence and degree of specimen fibrosis. All consecutive EUS-TA procedures were retrieved, and the specimens were graded for sample adequacy and fibrosis. The results were evaluated according to patients’ and tumor characteristics and the EUS-TA technique. In total, 407 patients (59% male, 70 [63–77] year old) were included; sample adequacy and diagnostic accuracy were 90.2% and 94.7%, respectively. Fibrosis was significantly more represented in tumors located in the head/uncinate process (p = 0.001). Tumor location in the head/uncinate (OR 0.37 [0.14–0.99]), number of needle passes ≥ 3 (OR 4.53 [2.22–9.28]), and the use of cell block (OR 8.82 [3.23–23.8]) were independently related to adequacy. Severe fibrosis was independently related to false negative results (OR 8.37 [2.33–30.0]). Pancreatic tumors located in the head/uncinate process showed higher fibrosis, resulting in EUS-TA with lower sample adequacy and diagnostic accuracy. We maintain that three or more needle passes and cell block should be done to increase the diagnostic yield.

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With the implementation of COVID-19 vaccine up-take, doubts regarding the impact of immunization on future fertility have begun to emerge. We have examined vaccine safety on male reproductive health. We set up a multicentre (three infertility centers), retrospective study in order to assess semen parameters and fertilization rate of one hundred-six men in a pairwise comparison between the first and second assisted reproduction technology (ART) attempt, performed respectively before and after COVID-19 vaccination. Median time (range) between the first vaccine dose and the second ART cycle was 75 days (39–112). Semen parameters did not change before and after the exposure. Fertilization rate was also similar before and after vaccination. Twenty-five patients (24%) were oligozoospermic before the vaccination while 26 (25%) after the exposure (P = 0.87). Severe asthenozoospermia were present in 11 patients before as well as after the exposure. No difference was observed even after considering different types of vaccines (mRNA or viral vector). COVID-19 vaccination did not affect sperm quality and fertilization capacity of men undergoing ART treatments and should be considered safe for men's reproductive health.