The Gray Matter project: modificating lifestyles to prevent dementia

As dementia aetiology is based on different bio-psychosocial factors, prevention strategies for dementia have recently focused on multi-domain interventions of individuals at risk and/or with a normative cognitive level, encouraging the lifestyle change through combined programs of physical activity, cognitive training, nutrition education and social activities (in chapter 1, a narrative review of these studies is presented). Most of the multidomain intervention aimed on the prevention of cognitive disease are carried on with elderly patients with a mild cognitive decline or on at-risk adult categories. 5 Caregivers of patients with dementia are considered as an at-risk category. The majority of them (86%) are represented by family members (prominently women) who are also defined as “informal caregivers”. They fulfil their caringgiving role from 7 to 11 h a day on average, up to 10-15 h when clinical conditions worsen 10. Informal caregivers have to cope with physical, psychological and social stressors that affect their health conditions and quality of life negatively (Eleuteri et al., 2016). The burdens of caregiving include many things that have been shown to increase the risk of cognitive decline, including chronic stress, social isolation, depression, decreased physical activity, and a shift in eating habits toward more fast food and significantly more weight compared with controls (Vitaliano et al., 1996). This could be connected with the important role that sleep plays between stress and metabolic health (Geiker et al., 2018). Being a caregiver has been found to be a factor affecting negatively sleep quality (Brummett et al., 2006). Interventions to promote positive lifestyles are, therefore, important in order to improve the caregivers’ general health and, specifically, to prevent the cognitive decline. In the second chapter, an article recently published specifies the importance of multimodal interventions in ameliorating caregivers’ health, since complex moderation and mediation effects exist between the different areas involved in the AD risk reduction. The third chapter will, finally, describe the results of the Gray Matter Project, a multidomain pilot RCT, firstly carried out done in Cache County, Utah designed to promote positive changes in lifestyle (exercise, nutrition, cognitive stimulation, social engagement, stress management, and sleep quality), specifically for the purpose of reducing AD risk in family caregivers of elderly with dementia

Increasing Patient Motivation and Adherence to Nutritional Care: The Importance to Overcome Psychological Barriers

AbstractEating habits are inseparably linked with people's physical and psychological health and well-being. Many factors impact on eating behavior and nutritional status in older adults. Motivational and multidisciplinary interventions have been shown to be highly effective in promoting healthy eating, especially in hospitalized patients, but are often overlooked or not considered. The aim of this chapter is to discuss how to overcome the psychological barriers that lead older patients away from an appropriate nutritional intake and the importance of motivational interventions for adherence to nutritional care, providing useful evidence and direction for further research

Aerobic training and angiogenesis activation in patients with stable chronic heart failure: a preliminary report.

The pathophysiology of chronic heart failure (CHF) involves multiple hystologic and molecular alterations. To determine the effects of physical training on circulating endothelial progenitor cells (EPCs), angiogenesis (angiogenin, angiopoietin-1 and -2, VEGF, Tie-2, SDF-1α) and inflammation (IL-6, CRP), we compared data obtained from 11 CHF pts before and after 3 months aerobic exercise training, to those from 10 non trained CHF pts (CHF-C group, age 64 + 2 years, NYHA 2). At the end of the study, EPCs count and AP-2 serum levels significantly increased in the CHF-TR group. These preliminary data suggest a significant effect of even a short program of physical training on angiogenic activation and endothelial dysfunction

Sorafenib induces cathepsin B-mediated apoptosis of bladder cancer cells by regulating the Akt/PTEN pathway. The Akt inhibitor, perifosine, enhances the sorafenib-induced cytotoxicity against bladder cancer cells

Sorafenib, a tyrosine kinase inhibitor, has been demonstrated to exert anti-tumor effects. However, the molecular mechanisms underlying its effects on bladder cancer remain unknown. Here, we evaluated the mechanisms responsible for the sorafenib-induced anti-tumor effects on 5637 and T24 bladder cancer cells. We demonstrated that sorafenib reduces cell viability, stimulates lysosome permeabilization and induces apoptosis of bladder cancer cells. These effects are dependent by the activation of cathepsin B released from lysosomes. The sorafenib-increased cathepsin B activity induced the proteolysis of Bid into tBid that stimulates the intrinsic pathway of apoptosis characterized by mitochondrial membrane depolarization, oxygen radical generation and cytochrome c release. Moreover, we found that cathepsin B enzymatic activity, induced by sorafenib, is dependent on its dephosphorylation via PTEN activation and Akt inactivation. Pretreatment with orthovanadate rescued bladder cancer cells from apoptosis. In addition, the Akt inhibitor perifosine increased the sensitivity of bladder cancer cells to sorafenib-induced cytotoxicity. Overall, our results show that apoptotic cell death induced by sorafenib in bladder cancer cells is dependent on cathepsin B activity and involved PTEN and Akt signaling pathways. The Akt inhibitor perifosine increased the cytotoxic effects of sorafenib in bladder cancer cells

Anti-viral state segregates two molecular phenotypes of pancreatic adenocarcinoma: potential relevance for adenoviral gene therapy

<p>Abstract</p> <p>Background</p> <p>Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer mortality for which novel gene therapy approaches relying on tumor-tropic adenoviruses are being tested.</p> <p>Methods</p> <p>We obtained the global transcriptional profiling of primary PDAC using RNA from eight xenografted primary PDAC, three primary PDAC bulk tissues, three chronic pancreatitis and three normal pancreatic tissues. The Affymetrix GeneChip HG-U133A was used. The results of the expression profiles were validated applying immunohistochemical and western blot analysis on a set of 34 primary PDAC and 10 established PDAC cell lines. Permissivity to viral vectors used for gene therapy, Adenovirus 5 and Adeno-Associated Viruses 5 and 6, was assessed on PDAC cell lines.</p> <p>Results</p> <p>The analysis of the expression profiles allowed the identification of two clearly distinguishable phenotypes according to the expression of interferon-stimulated genes. The two phenotypes could be readily recognized by immunohistochemical detection of the Myxovirus-resistance A protein, whose expression reflects the activation of interferon dependent pathways. The two molecular phenotypes discovered in primary carcinomas were also observed among established pancreatic adenocarcinoma cell lines, suggesting that these phenotypes are an intrinsic characteristic of cancer cells independent of their interaction with the host's microenvironment. The two pancreatic cancer phenotypes are characterized by different permissivity to viral vectors used for gene therapy, as cell lines expressing interferon stimulated genes resisted to Adenovirus 5 mediated lysis in vitro. Similar results were observed when cells were transduced with Adeno-Associated Viruses 5 and 6.</p> <p>Conclusion</p> <p>Our study identified two molecular phenotypes of pancreatic cancer, characterized by a differential expression of interferon-stimulated genes and easily recognized by the expression of the Myxovirus-resistance A protein. We suggest that the detection of these two phenotypes might help the selection of patients enrolled in virally-mediated gene therapy trials.</p

The International Sexual Health And Reproductive Health Survey (I-SHARE-1): A Multi-Country Analysis of Adults from 30 Countries Prior to and During the Initial COVID-19 Wave

Background: The COVID-19 pandemic forced billions of people to shelter in place, altering social and sexual relationships worldwide. In many settings, COVID-19 threatened already precarious health services. However, there is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of COVID-19 disease. To address this gap, our team organized a multi-country, cross-sectional online survey as part of a global consortium. Methods: Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service utilization, and we compared three months prior to and three months after policy measures to mitigate COVID-19. We used established indicators and analyses pre-specified in our protocol. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence using Cochrane methods. Descriptive analyses included 22,724 individuals in 25 countries. Five additional countries with sample sizes <200 were included in descriptive meta-analyses. Results: Respondents were mean age 34 years; most identified as women (15160; 66.7%), cis-gender (19432; 86.6%) and heterosexual (16592; 77.9%). Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%) people and 640 (14.1%) people reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063/15144, 7.0%) compared to the period before COVID-19 measures (1469/15887, 9.3%). COVID-19 measures impeded access to condoms (933/10790, 8.7%), contraceptives (610/8175, 7.5%), and HIV/STI testing (750/1965, 30.7%). Pooled estimates from meta-analysis indicate during COVID-19 measures, 32.3% (95% CI 23.9-42.1) of people needing HIV/STI testing had hindered access, 4.4% (95% CI 3.4-5.4) experienced partner violence, and 5.8% (95% CI 5.4-8.2) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy. Conclusion: Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings