New Seleno-Glyconjugates for Nutraceutical Application

Oxidative stress is a disequilibrium redox condition that occurs due to high concentration of prooxidant reactive species (RS) and, by comparison, a lower concentration of endogenous antioxidants in the body.1 Oxidative stress, caused by RS, is involved into the genesis of different pathologies such as inflammatory bowel disease, cardiovascular disease, Alzheimer’s disease, diabetes and cancer.2 Nutraceuticals could be used to prevent oxidative stress as an additional health benefit along with nutrition.1 The use of exogenous antioxidants can ameliorate this stressful condition and restore the redox disequilibrium.3 Polyphenols have a potential health-promoting effect, however, show a low bioavailability.4 For this reason, synthesis of organic seleniumcompounds combined to (poly)phenolic compounds could increase the solubility and exert their potential synergistic antioxidant effects. The approach proposed consists of preparing the D-ribose derivative 1 to obtain the donor 2 then employed to produce glycoconjugates containing well known (poly)phenols through a Mitsunobu reaction.5 To assess the bioactivity of selenoglycoconjugates, DPPH and ABTS antiradical assays were performed, while the effects on cell proliferation were preliminarily investigated on SH-SY5Y cells. The phenol moiety greatly affected both the antiradical efficacy and the mitochondrial redox activity. The glycoconjugates, especially at the highest tested concentrations, exhibited cytotoxic effects lower than that of unconjugated phenolic compounds, underlining the mitigating impact of selenosugar

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

Purpose: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT). Results: Vosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls. In xenograft models, vosaroxin reduced tumor growth and showed enhanced activity with RT; vosaroxin/RT combined was more effective than temozolomide/RT. Vosaroxin/ RT triggered rapid and massive cell death with characteristics of necrosis. A minor proportion of treated cells underwent caspase-dependent apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced autophagy, increasing necrosis. This was associated with increased recruitment of granulocytes, monocytes, and undifferentiated bone marrow-derived lymphoid cells. Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin. Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS) significantly compared with RT, vosaroxin alone, temozolomide, and temozolomide/RT in the U251-luciferase orthotopic model. Materials and Methods: Cellular, molecular, and antiproliferative effects of vosaroxin alone or combined with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in orthotopic intrabrain models using luciferasetransfected U251 cells by bioluminescence and magnetic resonance imaging. Conclusions: Vosaroxin demonstrated significant activity in vitro and in vivo in GBM models, and showed additive/synergistic activity when combined with RT in O6- methylguanine methyltransferase-negative and -positive cell lines

Dyslipidemia: evidence of efficacy of the pharmacological and non-pharmacological treatment in the elderly

The clinical decision to control risk factors for cardiovascular disease (CVD) in the elderly takes the followings into consideration: (1) the elderly life expectancy; (2) the elderly biological age and functional capacity; (3) the role of cardiovascular disease in the elderly group; (4) the prevalence of risk factors in the elderly; and (5) The effectiveness of treatment of risk factors in the elderly. A large number of studies showed the efficacy of secondary and primary prevention of dyslipidemia in the elderly. However, the only trial that included patients over 80 years was the Heart Protection Study (HPS). Statins are considered the first line therapy for lowering low-density lipoprotein cholesterol (LDL-C). Because lifestyle changes are very difficult to achieve, doctors in general tend to prescribe many drugs to control cardiovascular risk factors. However, healthy food consumption remains a cornerstone in primary and secondary cardiovascular prevention and should be implemented by everyone

Exploratory study on the associations between lifetime post-traumatic stress spectrum, sleep, and circadian rhythm parameters in patients with bipolar disorder

: The present study aimed at exploring whether lifetime post-traumatic stress spectrum symptoms are associated with chronotype in patients with bipolar disorder (BD). Moreover, we explored whether the chronotype can moderate the potential associations between lifetime post-traumatic stress spectrum symptoms and rest-activity circadian and sleep-related parameters. A total of 74 BD patients were administered the Trauma and Loss Spectrum Self-Report (TALS-SR) lifetime version for lifetime post-traumatic stress spectrum symptoms, the Pittsburgh Sleep Quality Index (PSQI) for self-reported sleep quality, and the Reduced Morningness-Eveningness Questionnaire (rMEQ) to discriminate evening chronotypes (ETs), neither chronotype (NT), and morning chronotype (MT). Actigraphic monitoring was used to objectively evaluate sleep and circadian parameters. Patients classified as ET reported significantly higher scores in the re-experiencing domain, as well as poorer sleep quality, lower sleep efficiency, increased wake after sleep onset, and delayed mid-sleep point compared with both NT and MT (p-value ≤ 0.05). Moreover, ET presented significantly higher scores in the TALS-SR maladaptive coping domain than NT and lower relative amplitude than MT (p-value ≤ 0.05). Moreover, higher TALS-SR total symptomatic domains scores were significantly correlated with poor self-reported sleep quality. Regression analyses showed that the PSQI score maintained the association with the TALS total symptomatic domains scores after adjusting for potentially confounding factors (age and sex) and that no interaction effect was observed between the chronotype and the PSQI. Conclusions: This exploratory study suggests that patients with BD classified as ET showed significantly higher lifetime post-traumatic stress spectrum symptoms and more disrupted sleep and circadian rhythmicity with respect to other chronotypes. Moreover, poorer self-reported sleep quality was significantly associated with lifetime post-traumatic stress spectrum symptoms. Further studies are required to confirm our results and to evaluate whether targeting sleep disturbances and eveningness can mitigate post-traumatic stress symptoms in BD

SEXUALIDADE FEMININA E MOVIMENTAÇÃO CORPORAL: UM RELATO DE EXPERIÊNCIA

Objetivo: relatar o desenvolvimento de ações educativas, na perspectiva feminista, que articularam sexualidade e movimentação corporal junto a mulheres da comunidade do Centro de Ciências da Saúde da Universidade Federal do Recôncavo da Bahia, contribuindo para o seu autoempoderamento. Método: estudo descritivo, com abordagem qualitativa, tipo relato de experiência, sobre pesquisa-ação, com metodologia educativa ativa e feminista. Participaram oito mulheres nas sete oficinas realizadas em Santo Antônio de Jesus, Bahia, de setembro a novembro de 2019. Utilizou-se, para as atividades de corpo e coleta de dados, técnicas educativas, referenciadas no arcabouço teórico e metodológico da pedagogia feminista e em metodologias ativas. Resultados: houve diferentes reflexões sobre identidade e as várias formas de ser mulher na sociedade atual. Conclusão: as ações educativas realizadas fortaleceram a troca de conhecimentos, o vínculo e a confiança do grupo, além da vivência coletiva do ser feminino. Descritores: Sexualidade. Mulheres. Corpo Humano. Empoderamento. Dança. Saúde.

Do Autistic Traits Correlate with Post-Traumatic Stress and Mood Spectrum Symptoms among Workers Complaining of Occupational Stress?

The adult autism subthreshold spectrum model appears to be a useful tool for detecting possible vulnerability factors in order to develop mental disorders in the contest of work-related stress. The aim of the present study is to analyze the relationship between autism, mood, and post-traumatic spectrum in a cohort of subjects complaining of work-related stress before the COVID-19 pandemic. The authors carried out a retrospective investigation of both medical records and self-assessment tools of a sample of subjects evaluated at the Occupational Health Department of a University hospital in central Italy. Data showed significant correlations between the AdAS spectrum, TALS-SR, and MOODS total and domain scores. A multiple linear regression evidenced that both the AdAS spectrum and TAL-SR significantly predict the MOODS scores. In particular, mediation analysis showed both a direct and indirect, mediated by TALS-SR, effect of the AdAS Spectrum on the MOODS-SR. These results corroborate the role of autistic traits in influencing the traumatic impact of work-related stress and the development of mood spectrum symptoms

Regorafenib in combination with silybin as a novel potential strategy for the treatment of metastatic colorectal cancer

Regorafenib, an oral multikinase inhibitor, has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients that have progressed after all standard therapies. However, novel strategies to improve tolerability and enhance anti-cancer efficacy are needed

Frailty Network in an Acute Care Setting: The New Perspective for Frail Older People

The incidence of elderly patients who come to the emergency room is progressively increasing. The specialization of the physician units might not be adequate for the evaluation of this complexity. The present study aimed to present a standard procedure, called ‘The Geriatric Frailty Network’, operating at the Policlinico Gemelli IRCCS Foundation, which is configured specifically for the level II assessment of frail elderly patients. This was a retrospective study in 1191 patients aged over 65, who were evaluated by the Geriatric Frailty Unit directly after emergency department admission for one year. All patients underwent multidimensional geriatric evaluation. Data were collected on demographics, co-morbidity, disease severity, and Clinical Frailty Scale. Among all patients, 723 were discharged directly from the emergency room with early identification of continuity of care path. Globally, 468 patients were hospitalized with an early assessment of frailty that facilitated the discharge process. The geriatric frailty network model aims to assist the emergency room and ward doctor in the prevention of the most common geriatric syndromes and reduce the number of incongruous hospitalization

Open Science @ UNIBO: il servizio di supporto a rete per le comunità di ricerca

Le forti spinte globali a favore dell’Open Access (OA) e dell’Open Science (OS) hanno sollecitato i sistemi bibliotecari delle università a rivedere servizi e competenze in funzione dei nuovi bisogni delle loro comunità di riferimento. Il Sistema Bibliotecario dell’Università di Bologna ha risposto a questi stimoli definendo un modello a rete a supporto dell’Open Access avviato sperimentalmente nella seconda metà del 2018. L’obiettivo strategico condiviso e co-gestito dall’intera comunità accademica è la promozione di prassi che consentano il libero accesso e il riuso delle pubblicazioni e dei dati della ricerca scientifica. Il servizio si struttura come una rete decentrata di punti di supporto collocati nelle biblioteche con il coordinamento centrale a cura della Biblioteca Digitale di Ateneo, AlmaDL. AlmaDL si occupa della formazione dei bibliotecari del servizio di supporto, fornisce loro assistenza specialistica anche in materia di diritto d’autore, coordina, monitora e sostiene il servizio con personale dedicato, oltre a offrire assistenza per la gestione FAIR dei dati di ricerca nel data repository di Ateneo e a garantire il raccordo istituzionale partecipando al Gruppo di lavoro Open Science di Ateneo. I punti di servizio offrono alle loro comunità scientifiche consulenza e orientamento, validano le pubblicazioni scientifiche depositate nel repository istituzionale, organizzano campagne di sensibilizzazione e rispondono alle esigenze specifiche delle comunità scientifiche. Ad oggi i bibliotecari coinvolti nel servizio sono 61; quasi 24.000 le pubblicazioni in OA e oltre 200 i dataset depositati nei repository istituzionali; 4830 le consulenze e 178 ore di formazione a cui hanno partecipato 1307 utenti. Il modello adottato ha presentato numerosi vantaggi rivelandosi sostenibile e attento alle specificità dei diversi ambiti disciplinari. Inoltre il continuo scambio di informazioni tra i nodi della rete permette lo sviluppo delle competenze e delle conoscenze in una continua ridefinizione del modello organizzativo e dei contenuti del servizio

Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: An open-label, 2 × 2 factorial, randomised phase 3 trial

Background: Whether addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel (EC-P) is favourable in adjuvant treatment of patients with node-positive breast cancer is controversial, as is the benefit of increased density of dosing. We aimed to address these questions in terms of improvements in disease-free survival. METHODS: In this 2 × 2 factorial, open-label, phase 3 trial, we enrolled patients aged 18-70 years with operable, node positive, early-stage breast cancer from 81 Italian centres. Eligible patients were randomly allocated in a 1:1:1:1 ratio with a centralised, interactive online system to receive either dose-dense chemotherapy (administered intravenously every 2 weeks with pegfilgrastim support) with fluorouracil plus EC-P (FEC-P) or EC-P or to receive standard-interval chemotherapy (administered intravenously every 3 weeks) with FEC-P or EC-P. The primary study endpoint was disease-free survival, assessed with the Kaplan-Meier method in the intention-to-treat population. Our primary comparisons were between dose schedule (every 2 weeks vs every 3 weeks) and dose type (FEC-P vs EC-P). This study is registered with ClinicalTrials.gov, number NCT00433420. FINDINGS: Between April 24, 2003, and July 3, 2006, we recruited 2091 patients. 88 patients were enrolled in centres that only provided standard-intensity dosing. After a median follow-up of 7·0 years (interquartile range [IQR] 4·5-6·3), 140 (26%) of 545 patients given EC-P every 3 weeks, 157 (29%) of 544 patients given FEC-P every 3 weeks, 111 (22%) of 502 patients given EC-P every 2 weeks, and 113 (23%) of 500 patients given FEC-P every 2 weeks had a disease-free survival event. For the dose-density comparison, disease-free survival at 5 years was 81% (95% CI 79-84) in patients treated every 2 weeks and 76% (74-79) in patients treated every 3 weeks (HR 0·77, 95% CI 0·65-0·92; p=0·004); overall survival rates at 5 years were 94% (93-96) and 89% (87-91; HR 0·65, 0·51-0·84; p=0·001) and for the chemotherapy-type comparison, disease-free survival at 5 years was 78% (75-81) in the FEC-P groups and 79% (76-82) in the EC-P groups (HR 1·06, 0·89-1·25; p=0·561); overall survival rates at 5 years were 91% (89-93) and 92% (90-94; 1·16, 0·91-1·46; p=0·234). Compared with 3 week dosing, chemotherapy every 2 weeks was associated with increased rate of grade 3-4 of anaemia (14 [1·4%] of 988 patients vs two [0·2%] of 984 patients; p=0·002); transaminitis (19 [1·9%] vs four [0·4%]; p=0·001), and myalgias (31 [3·1%] vs 16 [1·6%]; p=0·019), and decreased rates of grade 3-4 neutropenia (147 [14·9%] vs 433 [44·0%]; p<0·0001). Addition of fluorouracil led to increased rates of grade 3-4 neutropenia (354 [34·5%] of 1025 patients on FEC-P vs 250 [24·2%] of 1032 patients on EC-P; p<0·0001), fever (nine [0·9%] vs two [0·2%]), nausea (47 [4·6%] vs 28 [2·7%]), and vomiting (32 [3·1%] vs 15 [1·4%]). INTERPRETATION: In patients with node-positive early breast cancer, dose-dense adjuvant chemotherapy improved disease-free survival compared with standard interval chemotherapy. Addition of fluorouracil to a sequential EC-P regimen was not associated with an improved disease-free survival outcome