A third of the patients admitted with Acute coronary syndrome (ACS) have ST-elevation myocardial infarction (STEMI). Previous studies showed that females with STEMI have higher mortality than men.
...There exist significant disparities in outcomes among women of different races presenting with STEMI.
National inpatient sample (NIS) data was obtained from January 2016 to December 2018 for the hospitalization of female patients with STEMI. We compared outcomes, using an extensive multivariate regression analysis amongst women from different races. Our primary outcome was in-hospital mortality. Secondary outcomes were revascularization use, procedure complications, and healthcare utilization.
Of 202 223 female patients with STEMI; 11.3% were African American, 7.4% Hispanic, 2.4% Asian, and 4.3% another race. In-hospital mortality was higher in non-Caucasian groups. African American (adjusted odds ratio aOR 1.2; 95% confidence interval CI: 1.07-1.30; p < .01) and another race (aOR 1.37; 95% CI: 1.15-1.63; p < .01) had higher odds of mortality when compared with white women. African American (aOR 0.69; 95% CI: 0.62-0.72; p < .01), Hispanics (aOR 0.81; 95% CI: 0.74-0.88; p < .01), and Asian (aOR 0.79; 95% CI: 0.69-0.90; p < .01) had lower odds of percutaneous intervention (PCI) when compared with whites. African Americans had fewer odds of Coronary Artery Bypass Graft (CABG) and use of Mechanical Circulatory Support (MCS) during the index admission. Non-Caucasians had more comorbidities, complications, and healthcare utilization costs.
There are significant racial disparities in clinical outcomes and revascularization in female patients with STEMI. African American women have a higher likelihood of mortality among the different races. Females from minority groups are also less likely to undergo PCI.
Allosteric sites on proteins are targeted for designing more selective inhibitors of enzyme activity and to discover new functions. Acetylcholinesterase (AChE), which is most widely known for the ...hydrolysis of the neurotransmitter acetylcholine, has a peripheral allosteric subsite responsible for amyloidosis in Alzheimer's disease through interaction with amyloid β-peptide. However, AChE plays other non-hydrolytic functions. Here, we identify and characterise using computational tools two new allosteric sites in AChE, which have allowed us to identify allosteric inhibitors by virtual screening guided by structure-based and fragment hotspot strategies. The identified compounds were also screened for in vitro inhibition of AChE and three were observed to be active. Further experimental (kinetic) and computational (molecular dynamics) studies have been performed to verify the allosteric activity. These new compounds may be valuable pharmacological tools in the study of non-cholinergic functions of AChE.
The lack of an effective treatment for Alzheimer’ disease (AD), an increasing prevalence and severe neurodegenerative pathology boost medicinal chemists to look for new drugs. Currently, only ...acethylcholinesterase (AChE) inhibitors and glutamate antagonist have been approved to the palliative treatment of AD. Although they have a short-term symptomatic benefits, their clinical use have revealed important non-cholinergic functions for AChE such its chaperone role in beta-amyloid toxicity. We propose here the design, synthesis and evaluation of non-toxic dual binding site AChEIs by hybridization of indanone and quinoline heterocyclic scaffolds. Unexpectely, we have found a potent allosteric modulator of AChE able to target cholinergic and non-cholinergic functions by fixing a specific AChE conformation, confirmed by STD-NMR and molecular modeling studies. Furthermore the promising biological data obtained on human neuroblastoma SH-SY5Y cell assays for the new allosteric hybrid 14, led us to propose it as a valuable pharmacological tool for the study of non-cholinergic functions of AChE, and as a new important lead for novel disease modifying agents against AD.
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•Hybridization of indanone and quinoline heterocyclic scaffolds led to a new family of non-toxic dual binding site AChEIs.•A low nanomolar allosteric inhibitor of hAChE has been here identified.•The allosteric inhibitor of hAChE is able to increase neuritogenesis in a neuroblastoma cell culture.•A new pharmacological tool for the study of non-cholinergic functions of hAChE is here described.•Allosteric modulators of hAChE may be new leads for novel disease modifying agents against Alzheimer's disease.
BACKGROUND Small pericardial effusions are common with chronic hypothyroidism, but large pericardial effusion with tamponade or pre-tamponade physiology is a rare complication of severe uncontrolled ...hypothyroidism. Presentation of pericardial effusion of any etiology can range from being asymptomatic to hemodynamic instability with cardiac tamponade, depending on the amount and speed of accumulation of pericardial fluid, but pericardial effusion associated with hypothyroidism are usually small. Protracted medication non-adherence was a key factor in our patient's presentation. CASE REPORT We present a case of a woman in her 40s with a known history of autoimmune hypothyroidism with medication non-adherence for longer than 9 months who presented with fatigue, weight gain, limited physical activity, and exertional dyspnea with bilateral swelling of the upper and lower extremities. Examination revealed muffled heart sounds, positive JVD, and positive pulsus paradoxus. She had an elevated TSH, low free T4, and a high anti-thyroid peroxidase antibody level. Echocardiography revealed a large pericardial effusion with impending tamponade. Pericardiocentesis with pericardial drain was done and the patient's symptoms resolved quickly. The patient was restarted on a prior dose of levothyroxine 175 mcg. She had improved by the 3rd day of hospitalization; the pericardial drain was removed, and she was discharged with access to medication. Follow-up revealed complete resolution of her symptoms. CONCLUSIONS This case emphasizes the importance of recognition of hypothyroidism as the etiology of life-threatening large pericardial effusions, as it is treatable and recurrences are preventable. To prevent recurrence, it is important to achieve euthyroidism after treating an episode of pericardial effusion.
Quantitative structure-activity relationship modeling using machine learning techniques constitutes a complex computational problem, where the identification of the most informative molecular ...descriptors for predicting a specific target property plays a critical role. Two main general approaches can be used for this modeling procedure: feature selection and feature learning. In this paper, a performance comparative study of two state-of-art methods related to these two approaches is carried out. In particular, regression and classification models for three different issues are inferred using both methods under different experimental scenarios: two drug-like properties, such as blood-brain-barrier and human intestinal absorption, and enantiomeric excess, as a measurement of purity used for chiral substances. Beyond the contrastive analysis of feature selection and feature learning methods as competitive approaches, the hybridization of these strategies is also evaluated based on previous results obtained in material sciences. From the experimental results, it can be concluded that there is not a clear winner between both approaches because the performance depends on the characteristics of the compound databases used for modeling. Nevertheless, in several cases, it was observed that the accuracy of the models can be improved by combining both approaches when the molecular descriptor sets provided by feature selection and feature learning contain complementary information.
RESUMEN Introducción: A nivel mundial, cada año 3,2 millones de muertes son atribuidas a la diabetes, lo que equivale a una de cada 20 muertes, 8700 muertes cada día, seis cada minuto y por lo menos ...una de cada diez se producen en adultos de 35 a 64 años de edad. Objetivo: Proponer una estrategia de enfermería en el autocuidado de los adultos mayores con diabetes mellitus. Métodos: Estudio de intervención y desarrollo en el Policlínico “Dr. Rudesindo Antonio García del Rijoˮ del municipio y provincia de Sancti Spíritus, desde el año 2013 al 2017. Variables de estudio: edad, sexo, nivel de información de los adultos mayores, tipología de la diabetes mellitus, autocuidado de los adultos mayores y estado de salud de los adultos mayores con diabetes mellitus. Se utilizó entrevista estructurada a los adultos mayores con diabetes mellitus en la comunidad para conocer la mejoría del estado de salud, después de aplicada la estrategia se compararon las proporciones poblacionales mediante la prueba de McNemar. Resultados: Se lograron cambios significativos en el nivel de información de los adultos mayores, al finalizar se obtuvo 60,41 % aceptable. Después de aplicada la estrategia el autocuidado estaba presente en un 85,45 % y el estado de salud de los adultos mayores fue alto con un 84, 37 %. Conclusiones: Con las acciones y actividades que se incluyen en la estrategia de enfermería para el autocuidado de los adultos mayores con diabetes mellitus se lograron cambios significativos en el autocuidado.
Foundation: colorectal cancer is the most common neoplasm of the digestive system in older adults. In Cuba it is a major health problem due to its high incidence and mortality; it is the third cause ...of death in the general population.
Objective: to characterize older adults with colorectal cancer at the Rudesindo García del Rijo Sur Polyclinic in the Sancti Spíritus province.
Methods: a descriptive research was carried out at the Sur Rudesindo García del Rijo Polyclinic in the municipality and province of Sancti Spíritus, from January to March 2019. We worked with an intentional sample of 127 older adults, belonging to urban clinics. The variables analyzed were: age, sex, educational level, stage of colorectal cancer at diagnosis, health status, comorbidities, capacity and perception of self-care and survival. For the stage at diagnosis, the anatomoclinical classification was used, comorbidity was measured using the Charlson index and the Self-Care Capacity and Perception Test for the Elderly. The information was processed through percentage analysis. The results achieved were interpreted as numbers with their percentages.
Results: in the characterization of the sample, females, the age group between 70 and 79 years and the level of lower secondary education predominated. Stage II with a poor state of health and inadequate perception of self-care was the majority. Comorbidity was moderate with survival between 40 to 60 months.
Conclusions: women between 70 and 79 years of age and lower secondary education level predominated, stage II and inadequate perception of self-care also prevailed.
Abnormal connections between the ascending aortaand the cardiac chambers are rare, especially in thecontext of right-sided infective endocarditis(IE). Trans-thoracic echocardiography(TTE) with ...color-flow Dop-pler, transesophageal echocardiography(TEE), or bothmay be required for diagnosis. We present the case ofa woman admitted with right-sided heart failure(HF)symptoms. She had a previous history of tricuspid valveIE 30 years ago. TTE and TEE revealed an aorto-rightatrium fistula located just under the non-coronary cuspinto the right atrium at the level of the previously af-fected tricuspid valve. The Patient refused surgery andwas discharged home on HF medications. She has beenstable for the last 3 years. The peculiarity of this caseis the late symptomatic presentation of the aorto-atrialfistula and the unusual association to tricuspid valve IE.
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