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The cells possess several mechanisms to counteract the over-production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), including enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Moreover, an important sensor involved in the anti-oxidant response is KEAP1-NRF2-ARE signaling complex. Under oxidative stress (OS), the transcription factor NRF2 can dissociate from the KEAP1-complex in the cytosol and translocate into the nucleus to promote the transcriptional activation of anti-oxidant genes, such as heme oxygenase 1 and NADPH quinone oxidoreductase. Within this context, the activation of NRF2 response is further regulated by BACH1, a transcription repressor, that compete with the KEAP1-NRF2-ARE complex. In this work, we focused on the role of BACH1/NRF2 ratio in the regulation of the anti-oxidant response, proposing their antithetical relation as a valuable target for a therapeutic strategy to test drugs able to exert neuroprotective effects, notably in aging and neurodegenerative diseases. Among these, Down syndrome (DS) is a complex genetic disorder characterized by BACH1 gene triplication that likely results in the impairment of NRF2 causing increased OS. Our results revealed that BACH1 overexpression alters the BACH1/NRF2 ratio in the nucleus and disturbs the induction of antioxidant response genes ultimately resulting in the accumulation of oxidative damage both in Ts2Cje mice (a mouse model of DS) and human DS lymphoblastoid cell lines (LCLs). Based on this evidence, we tested Caffeic Acid Phenethyl Ester (CAPE) and the synthetic analogue VP961, which have been proven to modulate NRF2 activity. We showed that CAPE and VP961 administration to DS LCLs was able to promote NRF2 nuclear translocation, which resulted in the amelioration of antioxidant response. Overall, our study supports the hypothesis that BACH1 triplication in DS subjects is implicated in the alteration of redox homeostasis and therapeutic strategies to

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Nutritional guidelines suggest specific energy and protein requirements for patients with cancer. However, cancer patients, often malnourished, use self-made or web-based diets to ameliorate the prognosis of their disease. This review aimed to investigate the associations between post-diagnostic diet and prognostic outcomes in cancer patients. A systematic literature search was performed in Pubmed and Web of Science databases from inception to 30 October 2019, based on fixed inclusion and exclusion criteria. The risk of bias was assessed. A total of 29 prospective studies was identified. Breast (n = 11), colorectal (n = 9), prostate (n = 8) cancers are the most studied. Low-fat diet, healthy quality diet, regular consumption of fiber such as vegetables and high-quality protein intake are beneficial while Western diet (WD) and high consumption of saturated fats could be associated with a higher risk of mortality. Bladder (n = 1), gynecological (n = 1), lung, stomach, and pancreatic cancers still remain almost unexplored. This systematic review suggested that detrimental dietary patterns such as WD should be avoided but none of the food categories (meat, dairy products) should be eliminated in cancer patients’ diet. Further large prospective studies are needed to assess the role of post-diagnostic diet in patients with cancer.

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness. Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated. Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated? Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.

Background: Cutaneous relapse from endometrial cancer is a rare event, and often is part of a plurimetastatic disease with poor prognosis. Besides palliative chemotherapy, no consensus is present in literature about the specific treatment of skin metastases, in particular in order to improve symptoms. Objectives: In this paper the authors present a case of multi-metastatic endometrial cancer patient with also cutaneous metastasis, treated with palliative systemic therapy and electrochemotherapy. In particular the authors will describe the clinical, dermatoscopic, and pathological features of cutaneous metastases and their management. A literature review on cutaneous metastasis from endometrial cancer is also presented. Materials and Methods: A PubMed research was made using the terms "endometrial carcinoma", "skin", "cutaneous", "metastasis", and "spread". Discussion: The present case of unusual localization of skin metastases from endometrial cancer is the second described in the literature. The other known cases of cutaneous metastasis from endometrial cancer are summarized and reviewed. Electrochemotherapy can be proposed as an effective and safe loco-regional therapy for skin metastases, especially in case of multiple lesions. To the present authors' knowledge this is the first case of cutaneous metastases from endometrial cancer treated with electrochemotherapy.

Background: The role of surgery in recurrent ovarian cancer (ROC) is debated. Multiple prospective and retrospective series reported improved survival with optimal secondary surgical cytoreduction, but definitive results from randomized trials are needed. Up to the fourth cytoreductive surgery for recurrent disease in an attempt to improve patients' prognosis has been reported. Case report: We report the first case of multiple ROC in an Italian woman, 50 years old at diagnosis, who underwent 9 cytoreductive surgeries during her 17 years of disease with no serious postoperative complications. Conclusions: Multiple surgeries should not be considered as the standard treatment for ROC. In carefully selected patients, optimal cytoreductive surgery performed by highly specialized gynecologic oncologists might represent a useful tool in adjunction to chemotherapy for the management of ROC.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum- taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.