Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma.

Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor of children and young adults in which the principal driver is a fusion gene, EWSR1-FLI1. Although the essential role of EWSR1-FLI1 protein in the regulation of oncogenesis, survival, and tumor progression processes has been described in-depth, little is known about the regulation of chimeric fusion-gene expression. Here, we demonstrate that the active nuclear HDAC6 in EWS modulates the acetylation status of specificity protein 1 (SP1), consequently regulating the SP1/P300 activator complex binding to EWSR1 and EWSR1-FLI1 promoters.

Effectiveness of an Acute Care for Elders unit at a long-term care facility for frail older patients with COVID-19.

The Acute Care for Elders (ACE) is a model of care addressed to reduce the incidence of loss of self-care abilities of older adults occurring during hospitalization for acute illness. This observational study aimed to describe the effectiveness of an ACE unit at a long-term care facility to prevent functional decline (decrease in the Barthel Index score of >5 points from admission to discharge) in older adults with frailty (Clinical Frailty Scale score ≥5) and symptomatic COVID-19. Fifty-one patients (mean age: 80.

The combination of epigenetic drugs SAHA and HCI-2509 synergistically inhibits EWS-FLI1 and tumor growth in Ewing sarcoma.

Purpose: Epigenetic regulation is crucial in mammalian development and maintenance of tissue-cell specific functions. Perturbation of epigenetic balance may lead to alterations in gene expression, resulting in cellular transformation and malignancy. Previous studies in Ewing sarcoma (ES) have shown that the Nucleosome Remodeling Deacetylase (NuRD) complex binds directly to EWS-FLI1 oncoprotein and modulates its transcriptional activity.

Integrated Care on Leaving Hospital Against Medical Advice Among HIV-Infected People with Substance Use Disorders.

HIV-infected people with substance use disorders (HIV-SUDs) are at increased risk of leaving hospital against medical advice (LHAMA). The aim of this study was to evaluate the incidence of LHAMA in HIV-SUDs admitted to a patient-centered hospital where they receive integrated care, including healthcare, substance use treatment, and social support. Observational study was conducted at an urban acute-care university teaching hospital.

[Prognostic value of assessment tools on elderly patients with chronic advanced disease and end of life, admitted to an intermediate care centre].

Objective: To apply 3advanced chronic disease evaluation tools in elderly patients admitted to an intermediate and long-term care centre, and evaluate its relationship with mortality.

Methods: The NECPAL tool, PROFUND prognostic index, and Charlson comorbidity index were applied to 87 patients.

Results: The NECPAL tool identified 31 patients (35.

Metabolic syndrome among individuals with heroin use disorders on methadone therapy: Prevalence, characteristics, and related factors.

Background: Observational studies have reported a high prevalence of obesity and diabetes in subjects on methadone therapy; there are, however, limited data about metabolic syndrome. The aim of the study was to evaluate the prevalence of metabolic syndrome and related factors in individuals with heroin use disorder on methadone therapy.

Methods: A cross-sectional study in individuals with heroin use disorder on methadone therapy at a drug abuse outpatient center.

[Delirium prevention and treatment in elderly hip fracture].

The fracture of the proximal femur or hip fracture in the elderly usually happens after a fall and carries a high morbidity and mortality. One of the most common complications during hospitalization for hip fracture is the onset of delirium or acute confusional state that in elderly patients has a negative impact on the hospital stay, and prognosis, worsening functional ability, cognitive status and mortality. Also the development of delirium during hospitalization increases health care costs.

Analysis of DNA repair-related genes in breast cancer reveals CUL4A ubiquitin ligase as a novel biomarker of trabectedin response.

Trabectedin is more active in nucleotide excision repair (NER)-efficient and homologous recombination repair (HRR)-deficient cells. As up to 25% of sporadic breast tumors present somatic inactivation of the HRR pathway (BRCAness phenotype), we sought to characterize trabectedin effect in BRCA1-proficient and BRCA1-null breast cancer cell lines. We evaluated whether HRR and NER gene expression correlates with trabectedin sensitivity and explored the response predictive value of the CUL4A ubiquitin ligase, which ubiquitinates NER pathway members.

[Pharmacological treatment of dementia: when, how and for how long. Recommendations of the Working Group on Dementia of the Catalan Society of Geriatrics and Gerontology].

Dementia in general--and Alzheimer's disease (AD) in particular--are bound to loom large among the most acute healthcare, social, and public health problems of the 21st century. AD shows a degenerative progression that can be slowed down--yet not halted--by today's most widely accepted specific treatments (those based on cholinesterase inhibitors as well as those using memantine). There is enough evidence to consider these treatments advisable for the mild, moderate and severe phases of the illness.

[Informing of the diagnosis in dementia].

Dementia is a syndrome characterized by a progressive deterioration of cognitive functions, accompanied by psychiatric symptoms and behavioral disturbances that produce a progressive and irreversible disability. The way it should communicate the diagnosis of dementia is a key discussion point on which there is no unanimous agreement so far. The communicating of the diagnosis of dementia is a complex issue that affects not only, the patient but also to caregivers and health professionals who care and must conform to the ethical principles governing medical practice (autonomy, nonmaleficence, beneficence, and justice).

Lower Barthel Index scores predict less prescription of pharmacological therapy in elderly patients with Alzheimer disease.

Aims: To determine the factors associated with receiving specific treatment (cholinesterase inhibitors or/and memantine) for Alzheimer disease (AD) in elderly patients.

Methods: An observational study carried out in 289 consecutive outpatients aged >64 years with dementia. We collected data on specific AD therapy, sociodemographic variables, Barthel Index (BI), Lawton and Brody Index (LI), Mini Mental State Examination, Global Deterioration Scale (GDS), Charlson Index and the total number of drugs chronically prescribed.

[High prevalence of neuroleptic drug use in elderly people with dementia].

Background And Objectives: The management of psychological and behavioural symptoms associated with dementia frequently requires the use of neuroleptic drugs. The objective of this study was to determine the prevalence, characteristics and possible differential factors of people aged > or = 65 years with dementia who take or not neuroleptic drugs. The subgroup with Alzheimer disease was analysed.

Neurokinin-1 receptors located in human retinoblastoma cell lines: antitumor action of its antagonist, L-732,138.

Purpose: The authors have recently demonstrated that substance P and L-733,060 induce cell proliferation and cell inhibition, respectively, in human retinoblastoma cell lines. However, the presence of neurokinin-1 receptors has not been demonstrated in such cell lines, nor is it known whether other neurokinin-1 receptor antagonists exert antitumoral action against retinoblastoma cell lines. The purpose of this study was to demonstrate the presence of neurokinin-1 receptors in the human retinoblastoma cell lines WERI-Rb-1 and Y-79 and to study the growth inhibitory capacity of the neurokinin-1 receptor antagonist L-732,138 against those cell lines.