Visceral adiposity and cancer: Role in pathogenesis and prognosis

The prevalence of being overweight and obese has been expanded dramatically in recent years worldwide. Obesity usually occurs when the energetic introit overtakes energy expenditure from metabolic and physical activity, leading to fat accumulation mainly in the visceral depots. Excessive fat accumulation represents a risk factor for many chronic diseases, including cancer. Adiposity, chronic low-grade inflammation, and hyperinsulinemia are essential factors of obesity that also play a crucial role in tumor onset. In recent years, several strategies have been pointed toward boundary fat accumulation, thus limiting the burden of cancer attributable to obesity. While remodeling fat via adipocytes browning seems a tempting prospect, lifestyle interventions still represent the main pathway to prevent cancer and enhance the efficacy of treatments. Specifically, the Mediterranean Diet stands out as one of the best dietary approaches to curtail visceral adiposity and, therefore, cancer risk. In this Review, the close relationship between obesity and cancer has been investigated, highlighting the biological mechanisms at the basis of this link. Finally, strategies to remodel fat, including browning and lifestyle interventions, have been taken into consideration as a major perspective to limit excess body weight and tumor onset

Adoption and Implementation of the Surgical Safety Checklist: Improving Safety in an Italian Teaching Hospital

Although it is known that clinical risk management tools such as the Surgical Checklist lead to greater safety for patients and protection for the operators, clinical risk management units have much work to do to implement and spread the use of quality health care tools

Medical responsibility, insurance policies, new laws and European directives. Is it time to reform the status of Italian medical residents?

In Italy there is an ongoing debate on the need to clarify the legal aspects related to the clinical activities of medical residents. While residents attend university medical schools, specific policies should be implemented to guarantee their proper utilization in health organizations also for the direct and indirect legal responsibilities of patients health and safety. It seems necessary to create an uniform and clearer legal framework to surmount criticism of the utilization of residents. We recommend Ministries of University and Health to change the current training contract into a job-training one, in line with experiences for residents of other European countries. This initiative could promote a no-blame culture and also help Italian specialist doctors of future generations to be trained in order to move and be competitive across European country borders and finally promote the sustainability of the Italian public NHS through a patient-centred and inter-professional integrated approach

Variants in MARC1 and HSD17B13 reduce severity of NAFLD in children, perturb phospholipid metabolism, and suppress fibrotic pathways

Background & aims: Genome-wide association studies in adults have identified variants in HSD17B13 and MARC1 as protective against NAFLD. It is not known if they are similarly protective in children and, more generally, whether the peri-portal inflammation of pediatric NAFLD and lobular inflammation seen in adults share common genetic influences. Therefore, we aimed to: establish if these variants are associated with NAFLD in children, and to investigate the function of these variants in hepatic metabolism using metabolomics. Methods: 960 children (590 with NAFLD, 394 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MARC1. Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of samples. In silico tools were used to model the effect of rs2642438G>A (p.Ala165Thr) on MARC1. Results: rs72613567T>TA in HSD17B13 was associated with lower odds of NAFLD diagnosis (OR 0.7 (95%CI 0.6-0.9) and lower grade of portal inflammation (PA in MARC1 was associated with lower grade of hepatic steatosis (P=0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective allele, whereas MARC1 levels were not affected by genotype. Both variants showed downregulation of hepatic fibrotic pathways, upregulation of retinol metabolism and perturbation of phospholipid species. Modelling suggests that p.Ala165Thr would disrupt the stability and metal-binding of MARC1. Conclusions: There are shared genetic mechanisms between pediatric and adult NAFLD, despite their differences in histology. MARC1 and HSD17B13 are involved in phospholipid metabolism and suppress fibrosis in NAFLD

UC.183, UC.110, and UC.84 Ultra-Conserved RNAs Are Mutually Exclusive with miR-221 and Are Engaged in the Cell Cycle Circuitry in Breast Cancer Cell Lines.

In the human genome, there are about 600 ultra-conserved regions (UCRs), long DNA sequences extremely conserved in vertebrates. We performed a large-scale study to quantify transcribed UCR (T-UCR) and miRNA levels in over 6000 cancer and normal tissue samples to find possible correlation between these kinds of regulatory molecules. Our analysis evidenced several non-coding RNAs showing negative co-regulation with miRNAs; among them, we focused on miR-221 to investigate any relationship with its pivotal role in the cell cycle. We have chosen breast cancer as model, using two cell lines with different phenotypes to carry out in vitro treatments with siRNAs against T-UCRs. Our results demonstrate that the expression of uc.183, uc.110, and uc.84 T-UCRs is mutually exclusive with miR-221 and is engaged in the regulation of CDKN1B expression. In addition, tests with a set of anticancer drugs, including BYL719, AZD5363, AZD8055, AZD7762, and XL765, revealed the modulation of specific T-UCRs without alteration of miR-221 levels

Main clinical features in patients at their first psychiatric admission to Italian acute hospital psychiatric wards. The PERSEO study

BACKGROUND: Few data are available on subjects presenting to acute wards for the first time with psychotic symptoms. The aims of this paper are (i) to describe the epidemiological and clinical characteristics of patients at their first psychiatric admission (FPA), including socio-demographic features, risk factors, life habits, modalities of onset, psychiatric diagnoses and treatments before admission; (ii) to assess the aggressive behavior and the clinical management of FPA patients in Italian acute hospital psychiatric wards, called SPDCs (Servizio Psichiatrico Diagnosi e Cura = psychiatric service for diagnosis and management). METHOD: Cross-sectional observational multi-center study involving 62 Italian SPDCs (PERSEO – Psychiatric EmeRgency Study and EpidemiOlogy). RESULTS: 253 FPA aged <= 40 were identified among 2521 patients admitted to Italian SPDCs over the 5-month study period. About half of FPA patients showed an aggressive behavior as defined by a Modified Overt Aggression Scale (MOAS) score greater than 0 Vs 46% of non-FPA patients (p = 0.3651). The most common was verbal aggression, while about 20% of FPA patients actually engaged in physical aggression against other people. 74% of FPA patients had no diagnosis at admission, while 40% had received a previous psychopharmacological treatment, mainly benzodiazepines and antidepressants. During SPDC stay, diagnosis was established in 96% of FPA patients and a pharmacological therapy was prescribed to 95% of them, mainly benzodiazepines, antipsychotics and mood stabilizers. CONCLUSION: Subjects presenting at their first psychiatric ward admission have often not undergone previous adequate psychiatric assessment and diagnostic procedures. The first hospital admission allows diagnosis and psychopharmacological treatment to be established. In our population, aggressive behaviors were rather frequent, although most commonly verbal. Psychiatric symptoms, as evaluated by psychiatrists and patients, improved significantly from admission to discharge both for FPA and non-FPA patients

Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey

<p>Abstract</p> <p>Background</p> <p>The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications.</p> <p>Methods</p> <p>A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period.</p> <p>Results</p> <p>Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay.</p> <p>Conclusion</p> <p>Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.</p

Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the DMD gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)–microdystrophin (μDys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 × 1013 vector genomes per kilogram (vg/kg), 1 × 1014 vg/kg, and 2 × 1014 vg/kg; n = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-μDys5, and followed for 90 days after dosing. All dogs received prednisone (1 milligram/kilogram) for a total of 5 weeks from day-7 through day 28. We observed dose-dependent increases in tissue vector genome copy numbers; μDys5 protein in multiple appendicular muscles, the diaphragm, and heart; limb and respiratory muscle functional improvement; and reduction of histopathologic lesions. As expected, given that a truncated dystrophin protein was generated, phenotypic test results and histopathologic lesions did not fully normalize. All administrations were well tolerated, and adverse events were not seen. These data suggest that systemically administered AAV-microdystrophin may be dosed safely and could provide therapeutic benefit for patients with DMD