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The anti-inflammatory activity of the “Mela Rosa Marchigiana” (MRM) pulp callus ethanol Extract (MRME) was tested in different cellular models including (i) LPS-treated RAW 264.7; (ii) HUVEC exposed to short-term high Glucose (HG, 45 mM) or normal glucose (NG, 5 mM) concentrations; and (iii) HG (30 mN) and LPS-treated U937. To evaluate the anti-inflammatory effect of the extract, Nitric Oxide (NO) production was measured in RAW 264.6 cells, while IL-8, IL-1ß and MCP-1 expressions, along with modulation of some inflammation- or senescence-associated miRNAs (miR-21, miR-126, miR-17 and miR-217) were assessed in HUVECs and/or U937. MRME treatment reduced pro-inflammatory markers amount, suggesting a decreased generalised inflammatory response. Present findings indicate that MRME can contrast senescence- or HG-induced inflammation. Moreover, in HG- and LPS-induced inflammation, MRME reduced U937 monocyte activation by inhibiting mitochondrial respiration and inflammatory markers. Finally, the inhibitory potential of MRME on the digestive enzymes α-glucosidase, α-amylase and lipase activity was investigated. Our results support the idea that MRME has a positive effect on inhibition of endothelial/macrophage dysfunction under HG/senescence inflammatory conditions. Furthermore, the obtained results showed a modest inhibitory power of the extract (IC50 values: 2.98 ± 0.24, 1.77 ± 0.15, and 2.06 ± 0.31 mg/ml, respectively), which, however, could be of some help in decreasing the absorption of glucose and triglycerides.

Objective: Anterior mitral anular calcification, particularly in radiation heart disease, and previous valve replacement with destroyed intervalvular fibrosa are challenging for prosthesis sizing and placement. The Commando procedure with intervalvular fibrosa reconstruction permits double-valve replacement in these challenging conditions. We referenced outcomes after Commando procedures to standard double-valve replacements. Methods: From January 2011 to January 2022, 129 Commando procedures and 1191 aortic and mitral double-valve replacements were performed at the Cleveland Clinic, excluding endocarditis. Reasons for the Commando were severe calcification after radiation (n = 67), without radiation (n = 43), and others (n = 19). Commando procedures were referenced to a subset of double-valve replacements using balancing-score methods (109 pairs). Results: Between balanced groups, Commando versus double-valve replacement had higher total calcium scores (median 6140 vs 2680 HU, P = .03). Hospital outcomes were similar, including operative mortality (12/11% vs 8/7.3%, P = .35) and reoperation for bleeding (9/8.3% vs 5/4.6%, P = .28). Survival and freedom from reoperation at 5 years were 54% versus 67% (P = .33) and 87% versus 100% (P = .04), respectively. Higher calcium score was associated with lower survival after double-valve replacement but not after the Commando. The Commando procedure had lower aortic valve mean gradients at 4 years (9.4 vs 11 mm Hg, P = .04). After Commando procedures for calcification, 5-year survival was 60% and 59% with and without radiation, respectively (P = .47). Conclusions: The Commando procedure with reconstruction of the intervalvular fibrosa destroyed by mitral anular calcification, radiation, or previous surgery demonstrates acceptable outcomes similar to standard double-valve replacement. More experience and long-term outcomes are required to refine patient selection for and application of the Commando approach.

Introduction: Neoadjuvant chemotherapies for breast cancer (BC) are effective but potentially cardiotoxic, and expose long survivors at risk of chemotherapy-related cardiac dysfunction (CTRCD). Unfortunately, early screening for CTRCD has actual diagnostic limits. Myocardial extracellular volume (mECV) is a radiological marker used in cardiac CT scans and cardiac magnetic resonance for diagnosis and follow-up of CTRCD. It can be measured in whole-body CT (WB-CT) scan, routinely performed in patients at high risk of relapse, to evaluate CTRCD occurrence during oncological follow-up. Methods: 82 WB-CT scans were examined at baseline (T0) and during oncological follow-up at first year (T1) and fifth year (T5) after the end of neoadjuvant treatment. mECV was measured at 1 min (PP) and 5 min (DP) after contrast injection. 31 echocardiograms were retrieved in T1 to perform a linear correlation between mECV and left ventricular ejection fraction (LVEF). Results: mECV values in T0 were similar between the two groups both in PP and in DP. Significant results were found for PP values in T1 (37.0 % vs 32 %, p = 0.0005) and in T5 (27.2 % vs 31.2 %, p = 0.025). A cut-off value of 35 % in PP proved significant in T1 (OR = 12.4, p = 0.004), while mECV was inversely correlated with LVEF both in PP (adj-S = −3.54, adj-p = 0.002) and in DP (adj-S = −2.51, adj-p = 0.0002), suggesting a synergistic action with the age at diagnosis (p

Objective: During aortic valve reimplantation, cusp repair may be needed to produce a competent valve. We investigated whether the need for aortic valve cusp repair affects aortic valve reimplantation durability. Methods: Patients with tricuspid aortic valves who underwent aortic valve reimplantation from January 2002 to January 2020 at a single center were retrospectively analyzed. Propensity matching was used to compare outcomes between patients who did and did not require aortic valve cusp repair. Results: Cusp repair was performed in 181 of 756 patients (24%). Patients who required cusp repair were more often male, were older, had more aortic valve regurgitation, and less often had connective tissue disease. Patients who underwent cusp repair had longer aortic clamp time (124 ± 43 minutes vs 107 ± 36 minutes, P = .001). In-hospital outcomes were similar between groups and with no operative deaths. A total of 98.3% of patients with cusp repair and 99.3% of patients without cusp repair had mild or less aortic regurgitation at discharge. The median follow-up was 3.9 and 3.2 years for the cusp repair and no cusp repair groups, respectively. At 10 years, estimated prevalence of moderate or more aortic regurgitation was 12% for patients with cusp repair and 7.0% for patients without cusp repair (P = .30). Mean aortic valve gradients were 6.2 mm Hg and 8.0 mm Hg, respectively (P = .01). Ten-year freedom from reoperation was 99% versus 99% (P = .64) in the matched cohort and 97% versus 97%, respectively (P = .30), in the unmatched cohort. Survival at 10 years was 98% after cusp repair and 93% without cusp repair (P = .05). Conclusions: Aortic valve reimplantation for patients with tricuspid aortic valves has excellent long-term results. Need for aortic valve cusp repair does not affect long-term outcomes and should not deter surgeons from performing valve-sparing surgery.

Environmental problems due to climate change, that have been affecting our planet for years, are the main issues which prompted European Union to establish the ambitious target of achieving carbon neutrality by 2050. This occurrence encouraged all Member States to undergo significant changes of their energy sectors, favouring the extensive use of renewable energy sources. In this scenario, the European Union introduced Renewable Energy Communities, innovative energy systems based on a new model of renewable energy production, consumption and sharing, guaranteeing environmental, economic, energy and social benefits. The objective of this paper is twofold: firstly, to examine the regulatory framework of Member States and, secondly, to present a standardized procedure for the implementation of a Renewable Energy Community, an aspect not yet covered in scientific literature. The roadmap includes four main phases: a feasibility study involving an energy analysis of end users’ consumption and a general assessment; the aggregation of members as producers, consumers or prosumers forming a legal entity, considering different funding opportunities; the operating phase, involving plant construction and project validation by national authorities; the technical and economic management phase. The dynamic structure of the roadmap allows for adjustments to accommodate different regulatory contexts, member typologies and project aim.

Summary: Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01–2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the “2016 Call for Independent Drug Research”.

The Mela Rosa Marchigiana (MRM) pulp callus, kept alive since 2017 by monthly sub-cultures, was investigated and morphologically described. In the present paper, the MRM callus ethanolic Extract (MRME) was prepared from one of the 2022 callus sub-cultures and analysed by GC-MS and GC-FID. The investigation was carried out to test whether a long-term culture could affect either the amount or the bioactivity (or both) of the triterpenes produced by the callus. To this aim, the 2022 extract (MRME 2022) was compared to the extract prepared a few years ago (i.e., MRME 2019). Obtained results showed that the composition of both extracts was almost the same, thus revealing that the callus culture efficiency of triterpenes production was nearly unchanged over time. When analysing the biological effect of the extract, all experimental tests, including cell-free, in vitro, ex vivo, and in vivo assays, confirmed that MRME 2022 significantly protected cells, tissues, or whole organisms from oxidative stress-induced damage. Present results could lead to future studies to test MRME as a possible ingredient of a nutraceutical formulation for healthy aging or for the prevention of oxidative stress-associated pathologies.

Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

Summary: Background: The emergence of potentially effective new therapies for genetic forms of amyotrophic lateral sclerosis (ALS) necessitates the identification of biomarkers to facilitate early treatment, prior to the onset of motor symptoms. Here, we sought to investigate whether metabolic alterations are detectable in presymptomatic ALS gene mutation carriers, and whether such alterations precede neurofilament light chain (NfL) changes in serum. Methods: Between 02/2014 and 11/2021, we prospectively studied 60 presymptomatic ALS gene mutation carriers (40% male, age 48.7 ± 14.9; 28 C9orf72, 22 SOD1, 10 other) compared to 73 individuals from the same families (47% male, age 47.4 ± 12.9) without pathogenic mutations as controls. Bioimpedance analysis (BIA) and indirect calorimetry were performed, and Body Mass Index (BMI), Fat Mass (FM), Body Fat Percentage, Body Water (BW), Lean Body Mass (LBM), Extracellular Mass (ECM), Body Cell Mass (BCM), ECM/BCM ratio, Cells Percentage, Phase Angle, Resting Metabolic Rate (RMR), Metabolic Ratio (MR), and NfL were measured. Participants and evaluators were blinded regarding gene carrier status. Findings: Presymptomatic ALS gene carriers showed reduced LBM (p = 0.02), BCM (p = 0.004), Cells Percentage (p = 0.04), BW (p = 0.02), Phase Angle (p = 0.04), and increased ECM/BCM ratio (p = 0.04), consistently indicating a loss of metabolically active body cells. While in C9orf72 mutation carriers all tissue masses were reduced, only metabolically active tissue was affected in SOD1 mutation carriers. Unexpectedly, RMR (p = 0.009) and MR (p = 0.01) were lower in presymptomatic ALS gene carriers compared to non-carriers. NfL serum levels were similar in mutation carriers and non-carriers (p = 0.60). Interpretation: The observed metabolic phenomena might reflect reduced physical activity and/or preemptive, insufficient compensatory mechanisms to prepare for the later hypermetabolic state. As pre-symptomatic biomarkers we propose ECM/BCM ratio and Phase Angle for SOD1, and a 4-compartment affection in BIA for C9orf72 mutation carriers. Funding: This work was an investigator-initiated trial. On the German side, there was no institutional or industrial funding. On the Swedish side, this work was supported by grants from the Swedish Brain Foundation (grants nr. 2013-0279, 2016-0303, 2018-0310, 2020-0353), the Swedish Research Council (grants nr. 2012-3167, 2017-03100), the Knut and Alice Wallenberg Foundation (grants nr. 2012.0091, 2014.0305, 2020.0232), the Ulla-Carin Lindquist Foundation, Umeå University (223-2808-12, 223-1881-13, 2.1.12-1605-14) and the Västerbotten County Council (grants nr 56103-7002829), King Gustaf V:s and Queen Victoria's Freemason's Foundation.

Objective: To evaluate the outcomes of surgical resection of malignant primary cardiovascular tumors. Methods: From 1983 to 2018, 32 patients underwent surgical resection of malignant primary cardiovascular sarcoma at Cleveland Clinic. Mean age was 48 ± 15 years, and 19 (59%) were women. Outcomes are compared between those with complete resection and those without, and in relation to primary location. Results: The most common histologic subtypes were angiosarcoma (n = 8 [25%]) and high-grade undifferentiated sarcoma (n = 7 [22%]). Fourteen (44%) involved the left heart, 9 (28%) the right heart, 8 (25%) the pulmonary arteries, and 1 (3%) the aorta. There was clinical evidence of isolated extracardiac metastases in 8 (25%). Six (19%) patients were deemed unresectable at surgery, undergoing biopsy and palliative debulking followed by referral for definitive chemotherapy and/or radiation. The remaining 26 (81%) patients underwent 31 tumor resections with curative intent. Seven (22%) patients had previously undergone a resection or biopsy at another institution. There were 10 second-time resections, 2 third-time resections, 1 fourth-time resection, and no operative mortalities. Median survival was 3 years, with estimated survival at 6 months and 1, 5, and 10 years of 90%, 73%, 31%, and 17%, respectively. Of the 8 (25%) who were considered disease-free following surgery, 4 experienced recurrences during follow-up. Conclusions: Primary cardiac sarcoma continues to be a challenging disease with poor prognosis. Aggressive resection with curative intent, frequent surveillance for local and distant recurrence, and systemic and local multimodality treatment optimizes outcomes.

Objective: The aim was to adapt an instrument that evaluates the relationship between young individuals and health professionals to the Brazilian population, which will be called the Escala de Avaliação de Vínculo entre Jovens e Profissionais de Saúde (Youth Connectedness to Provider scale). Method: The questionnaire known as the Youth Connectedness to Provider scale consists of seven Likert-like questions. The translation, back-translation, evaluation by ten specialists, and pre-test with 43 adolescents and young adults aged between 10 and 24 years were performed to assess the clarity and reliability of meanings. The content validity index was calculated for each question. Subsequently, the clinical validation was performed with 83 patients aged 10–24 years old and Cronbach's alpha coefficient was calculated. Results: A content validity index >0.8 (considered satisfactory) was obtained for all items analyzed by experts and adolescents. At the clinical validation, it showed a high internal consistency (Cronbach’s alpha = 0.76). The questions showed a good correlation, except for the question about judgment (Spearman’s rho = 0.03–0.19). Conclusions: The scale adaptation showed an adequate agreement rate at the translation evaluation and a good reliability index in the questions. This instrument provides information on strengths and topics that require more attention from professionals to improve the relationship with their patients; it can be a valuable parameter in assessing the medical consultation quality.

Phytoplankton assemblages are privileged descriptors of the ecological status of marine ecosystems regularly included in routine monitoring programmes. The high spatial and temporal variability of phytoplankton and the intrinsic difficulties of species identifications, however, combine in making reiterate assessments of this component of marine biota particularly demanding. Coarse levels of taxonomic resolution (e.g., genus, family) or morpho-functional categories have been proposed to reduce identification efforts or to ease the analysis of phytoplankton assemblages for monitoring purposes, although with contrasting outcomes. A major issue is that, in the absence of control for the loss of information associated to these alternative approaches, their application may lead to poor representations of genuine spatial and/or temporal patterns of assemblages in relation to natural and anthropogenic sources of variation. We provided a new approach to reduce the efforts required to analyse phytoplankton assemblages that integrate morpho-functional classification of phytoplankton with the use of null models to estimate the consequent loss of information on species-level community patterns. Null models for information loss were built by randomly grouping the original species variables into a progressively decreasing number of groups, in order to identify the minimum number of aggregate variables needed to detect community patters as at species level. Aggregate variables were then defined as morpho-functional groups, by grouping species on the basis of a combination of morpho-functional traits, including general taxonomy, cell size, shape, elongation and complexity. We applied the approach to six case studies investigating the response of phytoplankton assemblages from marine and transitional water ecosystems under different environmental settings in areas spanning the world’s ocean, including coral atolls, mangroves, estuaries, coastal lagoons and inlets. The approach allowed obtaining parsimonious sets of morpho-functional groups, which were suitable to detect changes in phytoplankton assemblage structure as at species level in all case studies. Trait-based approaches to phytoplankton research and monitoring are crucial to shed light on processes underlying phytoplankton community assembly and dynamics in the face of global change. In this perspective, our framework incorporates cost-effectiveness, instances from traditional monitoring programmes aiming at the detection of community patterns, and the current need for a deeper understanding of functional responses of phytoplankton to environmental drivers.

We performed a cross-sectional parasitological survey to assess the prevalence of protozoa and helminth infection among 275 school-age children (SAC) living in rural and peri-urban areas located in different ecological zones of the Department of La Paz, Bolivia. Public health activities for the control of STH, based on the biannual administration of mebendazole to preschool and school children are implemented at national level since 1986.We found an overall prevalence of 82.2% for intestinal parasites, including protozoa (80%) and helminths (23.3%). Blastocystis and Entamoeba coli were the most prevalent protozoa (found in 44% and 20.7% of the SAC enrolled); as for helminths, Ascaris lumbricoides and Hymenolepis nana were diagnosed in 14.5% and 3.3% of the children, respectively, followed by Trichuris trichiura 1.4%, Enterobius vermicularis 1.4%, Strongyloides stercoralis 0.7% and hookworms 0.7%.Molecular characterization of Blastocystis positive samples evidenced three different subtypes (ST1, ST2, ST3) highlighting the risk of transmission also from animal reservoir. We found a significant difference in the distribution of intestinal parasitic infection (IPIs) by ecological zone (44/74. 59% in Andean highlands, 94/170, 88% in tropical lowlands and 88/94, 94% in the Yungas, p

Information about the early growth of infectious outbreaks is indispensable to estimate the epidemic spreading. A large number of mathematical tools have been developed to this end, facing as much large number of different dynamic evolutions, ranging from sub-linear to super-exponential growth. Of course, the crucial point is that we do not have enough data during the initial outbreak phase to make reliable inferences. Here we propose a straightforward methodology to estimate the epidemic growth dynamic from the cumulative infected data of just a week, provided a surveillance system is available over the whole territory. The methodology, based on the Newcomb-Benford Law, is applied to the Italian covid 19 case-study. Results show that it is possible to discriminate the epidemic dynamics using the first seven data points collected in fifty Italian cities. Moreover, the most probable approximating function of the growth within a six-week epidemic scenario is identified.

Objective: To compare perioperative outcomes of the elderly versus non-elderly patients on ERPs undergoing laparotomy for gynecologic surgery. Methods: From January 2016 to June 2017, patients undergoing elective laparotomies for gynecologic surgery were enrolled in a perioperative ERP protocol. Outcomes were compared between the elderly (age ≥ 70 years) and the non-elderly (age ≤ 69 years). Primary outcomes were length of stay and perioperative complication rates. Comparisons were performed using chi-squared tests or Fisher’s exact tests for categorical data and Student’s t-test or Wilcoxon rank-sum tests for continuous variables, with p

Introduction: Many authors have highlighted the management and outcomes of liver transplant patients with SARS -CoV2, however, there is a reduced experience identified with Hispanic or Latino patients [1]. We would like to share our experience with liver transplantation and SARS-CoV-2 infection (Real-time PCR identification) during 2020. Objectives: Describe the main infectious complications identified in patients with SARS-CoV2 and liver transplantation.Identify mortality rate among this group of patients and answer to therapies provided during their stay at the Hospital.Compare the mortality rate with other studies without Latin patients or with a reduced presence of them. Methods: This is an observational descriptive study carried out from May to August 2020 Results: 14 Hispanic patients were admitted to our institution (mean age 64 years; range: 57-76). Nine patients required hospitalization, and four patients were admitted to the intensive care unit (ICU). The most frequent risk factors were a history of arterial hypertension (n=8) and chronic kidney disease (n=6). The immunosuppression of these patients was based on antimetabolites (n = 9), calcineurin (n = 8), prednisolone (n = 4) and everolimus (n = 3). The onset of symptoms was six days approximately.All ICU patients receiving mechanical ventilation and renal replacement therapy for stage 3 acute renal failures. However, bacteremia caused by E. Coli, Citrobacter spp., and Staphylococcus aureus was present in three patients, an outcome that was not identified in the study population. The mortality rate was 28.5%. The mortality rate was higher than Webb et al 1 (18%) and other studies where rates were reported from 12% to 18%, and where the white population was predominant.The therapy provided in our institution was focused on tapering the immunosuppressive therapy attached with the use of dexamethasone. This treatment was given to six patients [4]. Conclusion: Our rate of mortality was higher compared with other similar studies. However, further future studies should include outcomes in the Hispanic population due to the social factors in addition to genetic factors that could be involved in higher mortality in ICU. Also, taking into account the increase in the number of cases, the follow-up of patients with liver diseases by telephone contact with transplant centers should be considered. Uncited references: [2,3,5]

Background & Aims: GPBAR1, also known as TGR5, is a G protein–coupled receptor activated by bile acids. Hepatic innate immune cells are involved in the immunopathogenesis of human liver diseases and in several murine hepatitis models. Here, by using genetic and pharmacological approaches, we provide evidence that GPBAR1 ligation attenuates the inflammation in rodent models of hepatitis. Material and methods: Hepatitis was induced by concanavalin A (Con A) or α-galactosyl-ceramide (α-GalCer). 6b-Ethyl-3a,7b-dihydroxy-5b-cholan-24-ol (BAR501), a selective agonist of GPBAR1, was administrated by o.s. Results: In the mouse models of hepatitis, the genetic ablation of Gpabar1 worsened the severity of liver injury and resulted in a type I NKT cells phenotype that was biased toward a NKT1, a proinflammatory, IFN-γ producing, NKT cells subtype. Further on, NKT cells from GPBAR1–/– mice were sufficient to cause a severe hepatitis when transferred to naïve mice. In contrast, GPBAR1 agonism rescued wild-type mice from acute liver damage and redirects the NKT cells polarization toward a NKT10, a regulatory, IL-10 secreting, type I NKT cell subset. In addition, GPBAR1 agonism significantly expanded the subset of IL-10 secreting type II NKT cells. RNAseq analysis of both NKT cells type confirmed that IL-10 is a major target for GPABR1. Accordingly, IL-10 gene ablation abrogated protection afforded by GPBAR1 agonism in the Con A model. Conclusion: Present results illustrate a role for GPBAR1 in regulating liver NKT ecology. Because NKT cells are an essential component of liver immune system, our data provide a compelling evidence for a GPBAR1-IL-10 axis in regulating of liver immunity. Keywords: Bile Acids, GPBAR1, Autoimmune Hepatitis, Natural Killer T Cells, NKT, Interleukin-10, IL-10

Obesity is constantly increasing worldwide due to the progressive globalization of sedentary lifestyle and diet rich in lipids and processed food. Cardiovascular complications and cancer are the two most fearsome long-term sequelae of obesity that justify the recent definition of this threaten as ‘obesity epidemic’. Shared biological pathways can be recognized for obesity-induced cardiovascular and oncological complications that might prompt targeted interventions with potentially double beneficial effect. The present review aims at summarizing main common biological pathways linking obesity with cardiovascular diseases and cancer in order to provide a research framework within which therapeutic strategies might have at the same time cardiovascular-protective and cancer-preventive effects.

Innovation is fundamental for all agri-food companies to increase competitiveness. Being extra-virgin olive oil (EVOO) a traditional food product (TFP), the main obstacle to innovation is its traditional nature. This study evaluated consumers’ acceptance for an EVOO with a naturally increased content of poliphenols, as it has been extracted through ultrasounds. This product has been compared with a set of emerging innovations that may be introduced in the next future. To this end, a choice experiment was carried out bent on the estimation of a Latent Class Model (LCM). A nationally-representative sample of EVOO consumers were involved in a web-based interview. The LCM analysis highlighted three segments of consumers: (1) innovative; (2) traditionalist; (3) cautious. Results showed that there is cluster of consumers willing to accept this innovation, therefore its introduction on the market appears to be possibly successful.

Background: The regional distribution of cerebral morphological alterations in primary lateral sclerosis (PLS) is considered to include the area III of the corpus callosum (CC). Objective: The study was designed to investigate regional white matter (WM) alterations in the callosal area III by T1 weighted magnetic resonance imaging (T1w-MRI) data in PLS patients compared with healthy controls, in order to identify atrophy and texture changes in vivo. Methods: T1w-MRI-based white matter mapping was used to perform an operator-independent CC-segmentation for the different areas of the CC in 67 PLS patients vs 82 matched healthy controls and vs 85 ALS patients. The segmentation was followed by texture analysis of the separated CC areas for the PLS patients vs controls and vs ALS patients. Results: PLS was associated with significant atrophy in the area III of the CC (but not in the other callosal segments), while the alterations in the ALS patients were much more variable and were not significant at the group level. Furthermore, significant regional alterations of the texture parameters entropy and homogeneity in this area were shown in PLS patients and in ALS patients. Conclusions: This T1w-MRI study demonstrated focused regional CC atrophy and texture alterations limited to the callosal area III (which comprises fibers projecting into the primary motor cortices) in PLS, in comparison to a higher variability in CC size in ALS.

We investigated the efficacy of different probiotics and bacteria used in dairy products to prevent the development of obesity and ameliorate established obesity in C57BL/6J mice fed a high fat diet (HFD). For the preventive efficacy, Lactobacillus rhamnosus GG, L. acidophilus LA1/K8, a mixture of Bifidobacterium lactis Bi1, B. breve Bbr8 and B. breve BL10 (B. mix), or a mixture of L. bulgaricus Lb2 and S. termophilus Z57 were given to mice before (2 weeks) and together with HFD (12 weeks). B. mix was selected for its anti-obesity activity and assessed in established obesity by feeding mice the HFD for 24 weeks and B. mix for the last 12 weeks. We found that B. mix was able to both prevent and ameliorate established obesity by reducing weight gain, adipose tissue fat accumulation, adipocyte size, and macrophage and CD4+ T cell infiltration, improving lipid profile and regulating leptin and cytokine secretion.

The Queensland preventive health survey is conducted annually to monitor the prevalence of behavioural risk factors in the north-east Australian state. Prompted by domestic and international trends in mobile telephone usage, the 2015 survey incorporated both mobile and landline telephone numbers from a list-based sampling frame. Estimates for landline-accessible and mobile-only respondents are compared to assess potential bias in landline-only surveys in the context of public health surveillance. Significant differences were found in subcategories of all health prevalence estimates considered (alcohol consumption, body mass index, smoking, and physical activity) from 2015 survey results. Results from Australian and international studies that have considered mobile telephone non-coverage bias are also summarised and discussed. We find that adjusting for sampling biases of telephone surveys by weighting does not fully compensate for the differences in prevalence estimates. However, predicted trends from previous years' surveys only differ significantly for the 2015 prevalence estimates of alcohol consumption. We conclude that the inclusion of mobile telephones into standard telephones surveys is important for obtaining valid, reliable and representative data to reduce bias in health prevalence estimates. Importantly, unlike some international experiences, the addition of mobiles telephones into the Queensland preventive health survey occurred before population trends were significantly affected.

Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of bone mass and increased fracture risk. Denosumab represents an anti RANKL (receptor activator of nuclear factor-kB ligand) monoclonal anti-body acting as inhibitor of osteoclasts formation, function, and survival, then increasing bone mass. Herein, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of Denosumab in saving bone health in prostate and breast cancer patients receiving respectively androgen deprivation therapy and adjuvant endocrine therapy. Moreover, selected patients have to be treated with Denosumab at the dose of 60 mg every six month or placebo. Outcomes studied included the bone mass density (BMD) increase at 24 and 36 months, BMD loss, reduction of fractures risk (in particular vertebral) at 24 and 36 months and safety (overall, serious adverse events – SAEs and discontinuation rate). Our results showed a reduction of the BMD loss up to 36 months both at the lumbar and femoral level and a BMD increase both at 24 and 36 months. It was also found a reduction in the number of new vertebral and femoral fractures at 24 and 36 months. Finally, our pooled analysis showed that Denosumab did not affect both the SAEs and therapy discontinuation risk. In conclusion, Denosumab administration can be considered effective and safe in the prevention and management of the above mentioned adverse events related to hormonal therapies designed for breast and prostate tumors. Keywords: Breast, Prostate, Cancer, Hormone, Denosumab, Fracture

Summary: Background: Although childhood trauma and violence against women are global public health issues, few population-based data from low-income and middle-income countries exist about the links between them. We present data from the UN Multi-country Study on Men and Violence in Asia and the Pacific, exploring the pathways between different forms of childhood trauma and violence against women. Methods: In this multicountry study, we interviewed multistage representative samples of men and women, aged 18–49 years, in Asia and the Pacific, using standardised population-based household surveys. Men were interviewed in six countries, and women in four. Respondents were asked questions about their perpetration or experience of intimate partner violence or non-partner sexual violence, childhood trauma, and harsh parenting (smacking their children as a form of discipline). We used maximum likelihood multivariate logit models to explore associations between childhood trauma and violence against women, and fitted path models to explore associations between experience and perpetration of child maltreatment. Findings: Between Jan 1, 2011, and Dec 1, 2012, 10 178 men and 3106 women completed interviews in this study, with between 815 and 1812 men per site and 477 and 1103 women per site. The proportion of men who experienced any childhood trauma varied between 59% (n=478, 95% CI 54·0–63·3; Indonesia rural site) and 92% (n=791, 89·4–93·8; Bougainville, Papua New Guinea). For women, the results ranged from 44% (n=272, 37·7–50·8; Sri Lanka) to 84% (n=725, 80·7–86·8; Bougainville, Papua New Guinea). For men, all forms of childhood trauma were associated with all forms of intimate partner violence perpetration. For women, all forms of childhood trauma were associated with physical intimate partner violence, and both physical and sexual intimate partner violence. There were significant, often gendered, pathways between men's and women's perpetration and experiences of childhood trauma, physical intimate partner violence, harsh parenting, and other factors. Interpretation: The data point to both a co-occurrence and a cycle of abuse, with childhood trauma leading to violence against women and further child maltreatment, which in turn increases the risk of experience or perpetration of violence during adulthood. Efforts to prevent both forms of violence would benefit from a meaningful integrated approach. Interventions should promote positive parenting, address inequality and the normalisation of violence across the life course, and transform men's power over women and children. Funding: Partners for Prevention. National studies were funded by the UN Population Fund in Bangladesh and China, UN Women in Cambodia and Indonesia, UN Develoment Programme in Papua New Guinea, and CARE in Sri Lanka.

Penile metastasis from prostate cancer represents a rare condition, associated with poor prognosis. In the literature, authors have reported less than 500 cases of secondary penile cancers, and among these cases of metastases, only 33% are from prostate cancer. Overall reported rate of survival is about 1-24 months. Here, we present an uncommon case of penile metastasis from prostatic adenocarcinoma, with particular focus on the role of computed tomography and magnetic resonance imaging in diagnosis and follow-up.

Background: Male perpetration of intimate partner violence (IPV) is under-researched. In this Article, we present data for the prevalence of, and factors associated with, male perpetration of IPV from the UN Multi-country Cross-sectional Study on Men and Violence in Asia and the Pacific. We aimed to estimate the prevalence of perpetration of partner violence, identify factors associated with perpetration of different forms of violence, and inform prevention strategies. Methods: We undertook standardised population-based household surveys with a multistage representative sample of men aged 18–49 years in nine sites in Bangladesh, China, Cambodia, Indonesia, Sri Lanka, and Papua New Guinea between January, 2011, and December, 2012. We built multinomial regression models of factors associated with lifetime violence perpetration: physical IPV, sexual IPV, both physical and sexual IPV, multiple emotional or economic IPV versus none, and calculated population-attributable fractions. In the analysis, we considered factors related to social characteristics, gender attitudes and relationship practices, victimisation history, psychological factors, substance misuse, and participation in violence outside the home. Findings: 10 178 men completed interviews in our study (between 815 and 1812 per site). The response rate was higher than 82·5% in all sites except for urban Bangladesh (73·2%) and Sri Lanka (58·7%). The prevalence of physical or sexual IPV perpetration, or both, varied by site, between 25·4% (190/746; rural Indonesia) and 80·0% (572/714; Bougainville, Papua New Guinea). When multiple emotional or economic abuse was included, the prevalence of IPV perpetration ranged from 39·3% (409/1040; Sri Lanka) to 87·3% (623/714; Bougainville, Papua New Guinea). Factors associated with IPV perpetration varied by country and type of violence. On the basis of population-attributable fractions, we show factors related to gender and relationship practices to be most important, followed by experiences of childhood trauma, alcohol misuse and depression, low education, poverty, and involvement in gangs and fights with weapons. Interpretation: Perpetration of IPV by men is highly prevalent in the general population in the sites studied. Prevention of IPV is crucial, and interventions should address gender socialisation and power relations, abuse in childhood, mental health issues, and poverty. Interventions should be tailored to respond to the specific patterns of violence in various contexts. Physical and sexual partner violence might need to be addressed in different ways. Funding: Partners for Prevention—a UN Development Programme, UN Population Fund, UN Women, and UN Volunteers regional joint programme for gender-based violence prevention in Asia and the Pacific; UN Population Fund Bangladesh and China; UN Women Cambodia and Indonesia; UN Development Programme in Papua New Guinea and Pacific Centre; and the Governments of Australia, the UK, Norway, and Sweden.

Background: Rape perpetration is under-researched. In this study, we aimed to describe the prevalence of, and factors associated with, male perpetration of rape of non-partner women and of men, and the reasons for rape, from nine sites in Asia and the Pacific across six countries: Bangladesh, China, Cambodia, Indonesia, Papua New Guinea, and Sri Lanka. Methods: In this cross-sectional study, undertaken in January 2011–December 2012, for each site we chose a multistage representative sample of households and interviewed one man aged 18–49 years from each. Men self-completed questions about rape perpetration. We present multinomial regression models of factors associated with single and multiple perpetrator rape and multivariable logistic regression models of factors associated with perpetration of male rape with population-attributable fractions. Findings: We interviewed 10 178 men in our study (815–1812 per site). The prevalence of non-partner single perpetrator rape varied between 2·5% (28/1131; rural Bangladesh) and 26·6% (225/846; Bougainville, Papua New Guinea), multiple perpetrator rape between 1·4% (18/1246; urban Bangladesh) and 14·1% (119/846; Bougainville, Papua New Guinea), and male rape between 1·5% (13/880; Jayapura, Indonesia) and 7·7% (65/850; Bougainville, Papua New Guinea). 57·5% (587/1022) of men who raped a non-partner committed their first rape as teenagers. Frequent reasons for rape were sexual entitlement (666/909; 73·3%, 95% CI 70·3–76·0), seeking of entertainment (541/921; 58·7%, 55·0–62·4), and as a punishment (343/905; 37·9%, 34·5–41·4). Alcohol was a factor in 249 of 921 cases (27·0%, 95% CI 24·2–30·1). Associated factors included poverty, personal history of victimisation (especially in childhood), low empathy, alcohol misuse, masculinities emphasising heterosexual performance, dominance over women, and participation in gangs and related activities. Only 443 of 1933 men (22·9%, 95% CI 20·7–25·3) who had committed rape had ever been sent to prison for any period. Interpretation: Rape perpetration committed by men is quite frequent in the general population in the countries studied, as it is in other countries where similar research has been undertaken, such as South Africa. Prevention of rape is essential, and interventions must focus on childhood and adolescence, and address culturally rooted male gender socialisation and power relations, abuse in childhood, and poverty. Funding: Partners for Prevention—a UN Development Programme, UN Population Fund, UN Women, and UN Volunteers regional joint programme for gender-based violence prevention in Asia and the Pacific; UN Population Fund Bangladesh and China; UN Women Cambodia and Indonesia; United Nations Development Programme in Papua New Guinea and Pacific Centre; and the Governments of Australia, the UK, Norway, and Sweden.

Objective: To explore recurrent themes in diaries kept by intensive care unit (ICU) staff during the coronavirus disease 2019 (COVID-19) pandemic., Design: Qualitative study., Setting: Two ICUs in a tertiary level hospital (Milan, Italy) from January to December 2021., Methods: ICU staff members wrote a digital diary while caring for adult patients hospitalized in the intensive care unit for >48 hours. A thematic analysis was performed., Findings: Diary entries described what happened and expressed emotions. Thematic analysis of 518 entries gleaned from 48 diaries identified four themes (plus ten subthemes): Presenting (Places and people; Diary project), Intensive Care Unit Stay (Clinical events; What the patient does; Patient support), Outside the Hospital (Family and topical events; The weather), Feelings and Thoughts (Encouragement and wishes; Farewell; Considerations)., Conclusion: The themes were similar to published findings. They offer insight into care in an intensive care unit during a pandemic, with scarce resources and no family visitors permitted, reflecting on the patient as a person and on daily care. The staff wrote farewell entries to dying patients even though no one would read them., Implications for Clinical Practice: The implementation of digital diaries kept by intensive care unit staff is feasible even during the COVID-19 pandemic. Diaries kept by staff can provide a tool to humanize critical care. Staff can improve their work by reflecting on diary records., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In the intensive care unit, invasive devices can be accidentally removed by the patient or by the operators, increasing workload, staff stress level and hospitalisation costs., Objective: to know the incidence of accidental removal of devices in critical patients, to identify their cause, when they occur and if they are repositioned., Methods: Retrospective observational study carried out in an academic, tertiary-level critical care department composed of three intensive care units. All adult patients recovered between 2011 and 2018 were enrolled. We calculated rates per 1000 device-years., Results: In the study period 10514 patients (194372 device-days) were admitted to the intensive care units and the number of reported accidental removal of devices was 451, corresponding to a rate of 2.3 episodes per 1000 device-days (95% confidence interval: 2.1-2-5). The overall rates of accidental removals were as follows: gastric tubes 10.2 (n = 270), intracranial devices 3.9 (n = 9), endotracheal tubes 2.4 (n = 27), central venous catheters and arterial catheters 1.5 (n = 92), peripheral intravenous catheters 1.2 (n = 25), surgical drains 0.5 (n = 15), urinary catheters 0.4 (n = 11), Extra Corporeal Membrane Oxygenation cannulas 0.4 (n = 1), tracheostomy cannulas 0.1 (n = 1)., Conclusion: Compared to the literature, this study shows fewer incidents of accidental removal of devices. The number of accidental removals could be an indicator of the quality and safety of the care., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Radiofrequency Ablation is the most widely performed percutaneous treatment for Hepatocellular Carcinoma. This multicentre study was aimed at assessing the complication, overall survival and disease-free survival rates in cirrhotic patients with single Hepatocellular Carcinoma nodule ≤3 cm undergoing Radiofrequency Ablation., Methods: Data of 365 patients (59% males; mean age 67 ± 8 years), Child-Pugh A/B, with single Hepatocellular Carcinoma nodule ≤3 cm (tumours >2-3 cm = 127/236), showing complete necrosis after Radiofrequency Ablation between 1998 and 2010 in 7 Italian Centers were retrospectively reviewed. Complication, overall survival and disease-free survival rates were analyzed as main clinical end-points., Results: Major complications were observed in 8 patients (2.2%) and minor complications in 23 patients (6.3%). The 3-, and 5-year overall survival rates were 80% and 64%. One hundred and seven patients (29.5%) died, being 41 deaths (38.3%) Hepatocellular Carcinoma-related. At multivariate analysis only age (p = 0.04; OR 2.29), ascites (p < 0.001; OR 3.74) and Child-Pugh class ≥B8 (p = 0.003; OR 2.42) were confirmed as independent predictors for overall survival. The disease-free survival rates at 3- and 5-year were 50%, and 41.8%., Conclusions: Radiofrequency Ablation is an effective and safe tool for the treatment of single Hepatocellular Carcinoma ≤3 cm providing excellent 5-year overall survival and disease-free survival rates. Patient's age and liver status appeared as main determinants of outcome., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The value of ultrasound (US) in assessing gastrointestinal diseases is well documented, but its demand in clinical practice is unknown. This survey evaluated the demand for bowel US in Italy., Methods: Twelve sonographers of the Gastroenterology Section of the Italian Society of Ultrasound participated in a 1-month survey; they compiled a questionnaire assessing total number of patients referred for abdominal US and for gastrointestinal tract US, type of referring physician, indications and results of examinations., Results: The survey included 2424 examinations, 586 of which (24%) investigated the gastrointestinal tract: 280 for signs or symptoms and 268 for follow-up of pre-existing gastrointestinal diseases. Referring physicians were mainly gastroenterologists (78%) and general practitioners (13%). Organic lesions were found or suspected in 292 examinations., Conclusions: Bowel US is used in Italy in routine practice, mainly by gastroenterologists and general practitioners, both for follow-up of pre-existing diseases and for gastrointestinal complaints., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Case Report: We report the unusual case of an African patient who underwent a liver biopsy for a chronic HBV-related hepatitis, whose histological sample also unexpectedly revealed elements diagnostic for schistosomiasis. The patient was only mildly symptomatic for the Schistosoma infestation; stool examination confirmed the presence of parasitic eggs. Hepatitis B virus (HBV)-schistosomiasis co-infection is particularly rare in Western countries. Only the identification of some pathological elements atypical for HBV infection by means of step sections in the liver biopsy sample allowed us to disclose the unsuspected diagnosis., Conclusions: Since migratory flows have increased, the number of foreign people being referred to our hospitals has increased. Patients coming from areas endemic for infectious diseases that are absent in Western countries must be carefully evaluated, taking into account possible unexpected co-infections, including in the setting of pathological studies of liver biopsies.