Overall, the studies converged to reveal the complexity of the anti-cancer potential of Sildenafil. Thus, through our review we aimed to present an updated and simplified picture of such repurposing of Sildenafil in the field of oncology.This review outlines the discovery and development of a novel series of 1-[4-2-aminoethoxy)phenylcarbonyl]- 3,5-bis-(benzylidene)-4-piperidones 5-8 as potential drug candidates over the last 15 years in our laboratory. Many of these compounds demonstrate excellent cytotoxic properties and are often more potent than contemporary anticancer drugs. Two highly important features of many of these molecules are first, the greater tumour-selective toxicity and second, the ability of these molecules to act as modulators of multi-drug resistance. The modes of action of some of the potent compounds are by apoptosis induction, generation of reactive oxygen species, activation of certain caspases and affecting mitochondrial functions. These molecules also display promising antimalarial and antimycobacterial properties. In a short term toxicity study, these molecules are well tolerated in mice. Structure-activity relationships, and a drug delivery system along with pharmacokinetic studies and metabolic stability of these compounds have been presented. The positive characteristics associated the series 5-8 warrants their further evaluations as candidate antineoplastic drug candidates.Malaria remains a serious problem in global public health, particularly widespread in South America and in tropical regions of Africa and Asia. Chemotherapy is actually the only way to treat this poverty-related disease, since an effective vaccine is not currently available. However, the onset of resistance to the most common antimalarial drugs sometimes makes the current therapeutic regimen problematic. Therefore, the identification of new targets for a new drug discovery process is an urgent priority. In this context, falcipain-2 and falcipain-3 of P. falciparum represent the key enzymes in the life-cycle of the parasite. Both falcipain-2 and falcipain-3 are involved in hemoglobin hydrolysis, essential pathway to provide free amino acids for the parasite metabolic needs. In addition, falcipain-2 is involved in cleaving ankirin and band 4.1 protein, cytoskeletal elements essential for the stability of red cell membrane. This review article is focused on the most recent and effective inhibitors of falcipain-2 and falcipain-3, with a particular attention to peptide, peptidomimetic or nonpeptide inhibitors which targeted one or both the malarial cysteine proteases, endowed with a consistent activity against P. falciparum.A 24-yo female was admitted for acute renal failure, melanoderma, hyponatremia and hyperkalemia. The clinical suspicion of Addison’s disease was confirmed by laboratory test and the appropriate replacement therapy with corticosteroids and fludrocortisone was started. In the mean-time primary hypothyroidism and diabetes mellitus type 1 were disclosed and treated, thus fulfilling a diagnosis of autoimmune polyendocrine syndrome type 2. Eighteen months later she was admitted for right sided heart failure. The work-up allowed to diagnose pulmonary arterial hypertension. Here we report the clinical course and discuss the putative link between these two rare diseases.Tetrahydrobipterin (BH4) is a pivotal enzymatic cofactor required for the synthesis of serotonin, dopamine and nitric oxide. BH4 is essential for numerous physiological processes at periphery and central level, such as vascularization, inflammation, glucose homeostasis, regulation of oxidative stress and neurotransmission. BH4 de novo synthesis involves the sequential activation of three enzymes, the major controlling point being GTP cyclohydrolase I (GCH1). Complementary salvage and recycling pathways ensure that BH4 levels are tightly kept within a physiological range in the body. Even if the way of transport of BH4 and its ability to enter the brain after peripheral administration is still controversial, data showed increased levels in the brain after BH4 treatment. Available evidence shows that GCH1 expression and BH4 synthesis are stimulated by immunological factors, notably pro-inflammatory cytokines. Once produced, BH4 can act as antiinflammatory molecule and scavenger of free radicals protecting against oxidative stress. At the same time, BH4 is prone to autoxidation, leading to release of superoxide radicals contributing to inflammatory processes, and to production of BH2, an inactive form of BH4, reducing its bioavailability. Alterations in BH4 levels have been documented in many pathological situations, including Alzheimer’s disease, Parkinson’s disease and depression, in which increased oxidative stress, inflammation and alterations in monoaminergic function are described. This review aims at providing an update of the knowledge about metabolism and role of BH4 in brain function, from preclinical to clinical studies, addressing some therapeutic implications.

Engagement in the arts may have health benefits for older adults. Most research has focused on music and dance; less is known about the benefits of other arts interventions. The purpose of this study was to examine the effects of visual (ceramics and collage) and literary arts (storytelling and writing) on well-being.

We used mixed methods to examine the effects of a 12-week visual or literary arts intervention on well-being. Adults age 55 and over from four housing sites were assigned to start an intervention immediately (intervention) or wait 12weeks (controls). The study included pre/post-test measures of well-being and focus groups about perceived benefits.

Compared to controls, participants in the ceramics intervention had significant improvements in interest in life and mastery, while no changes were observed after the storytelling intervention. Seven psychosocial benefits were identified .

Participation in visual and literary arts for older adults was associated with well-being media.

Participation in visual and literary arts for older adults was associated with well-being media.In response to rising numbers of opioid overdose deaths, primary care providers have been called on to play a greater role in delivering buprenorphine treatment for opioid use disorder. However, policy makers and providers have raised concerns that expanding treatment access may reduce treatment quality and that primary care providers are not well equipped to deliver buprenorphine treatment. We investigated two research questions in response to these concerns How did buprenorphine treatment use and quality change in North Carolina Medicaid from 2014 to 2017, and how did buprenorphine treatment quality differ between primary care providers and specialists in North Carolina Medicaid during this period? We measured buprenorphine treatment quality as patients’ retention in treatment and providers’ adherence to treatment guidelines. We found that the number of enrollees receiving medication treatment for opioid use disorder increased substantially, but the percentage of enrollees with the disorder receiving treatment remained low. The quality of buprenorphine treatment increased during the study period, and primary care providers provided care of comparable or higher quality compared with that of other providers. Treatment quality for buprenorphine treatment is improving, but there remains room for improvement in both use and quality. Our results support the role of primary care providers in expanding treatment for opioid use disorder.Millions of older Americans are homebound and may benefit from home-based medical care. We characterized the receipt of this care among community-dwelling, fee-for-service Medicare beneficiaries ages sixty-five and older surveyed in the National Health and Aging Trends Study between 2011 and 2017. Five percent of those surveyed received any home-based medical care between 2011 and 2017 (mean follow-up time per person was 3.4 years), and 75 percent of home-based medical care recipients were homebound. Only 11 percent of the total homebound population (approximately 4.4 million fee-for-service Medicare beneficiaries in 2017) received any home-based medical care between 2011 and 2017. Receipt of home-based medical care was more common among homebound beneficiaries living in metropolitan areas and assisted living facilities, which suggests that geographic factors create operational efficiencies for home-based medical care practices that may improve their financial sustainability within the fee-for-service reimbursement setting. The significant unmet needs of this high-need, high-cost population and the known health and cost benefits of home-based medical care should spur stakeholders to expand the availability of this care.Health systems continue to grow in size. Financial integration-the ownership of hospitals or physician practices-often has anticompetitive effects that contribute to the higher prices for health care seen in the US. To determine whether the potential harms of financial integration are counterbalanced by improvements in quality, we surveyed nationally representative samples of hospitals (n = 739) and physician practices (n = 2,189), stratified according to whether they were independent or were owned by complex systems, simple systems, or medical groups. The surveys included nine scales measuring the level of adoption of diverse, quality-focused care delivery and payment reforms. Scores varied widely across hospitals and practices, but little of this variation was explained by ownership status. Quality scores favored financially integrated systems for four of nine hospital measures and one of nine practice measures, but in no case favored complex systems. Greater financial integration was generally not associated with better quality.Food insecurity predicts poorer health, yet how it relates to health care use and costs in Canada remains understudied. Linking data from the Canadian Community Health Survey to hospital records and health care expenditure data, we examined the association of food insecurity with acute care hospitalization, same-day surgery, and acute care costs among Canadian adults, adjusting for sociodemographic characteristics. Compared with fully food-secure adults, marginally, moderately, and severely food-insecure adults presented 26 percent, 41 percent, and 69 percent higher odds of acute care admission and 15 percent, 15 percent, and 24 percent higher odds of having same-day surgery, respectively. Conditional on acute care admission, food-insecure adults stayed from 1.48 to 2.08 more days in the hospital and incurred $400-$565 more per person-year in acute care costs than their food-secure counterparts, with this excess cost representing 4.4 percent of total acute care costs. Programs reducing food insecurity, such as child benefits and public pensions, and policies enhancing access to outpatient care may lower health care use and costs.The coronavirus disease 2019 (COVID-19) pandemic has highlighted the importance of intensive care unit (ICU) beds in preventing death from the severe respiratory illness associated with COVID-19. However, the availability of ICU beds is highly variable across the US, and health care resources are generally more plentiful in wealthier communities. We examined disparities in community ICU beds by US communities’ median household income. We found a large gap in access by income 49 percent of the lowest-income communities had no ICU beds in their communities, whereas only 3 percent of the highest-income communities had no ICU beds. Income disparities in the availability of community ICU beds were more acute in rural areas than in urban areas. Policies that facilitate hospital coordination are urgently needed to address shortages in ICU hospital bed supply to mitigate the effects of the COVID-19 pandemic on mortality rates in low-income communities.