Determinants of Government Expenditures with Health Insurance Beneficiaries in the Brazilian Health System.

: The Brazilian health system provides healthcare financed by the public and private sector, being the first designed to encompass universal healthcare coverage delivered to the population without charge to patients (Sistema Único de Saúde, SUS), whilst the second refers to healthcare coverage delivered for individuals with the capacity to pay for assistance through health insurance or out-of-pocket disbursements. Health insurance companies with beneficiaries receiving publicly financed healthcare from the SUS are required to provide the reimbursement of healthcare expenditures to the government, considering that the health insurance beneficiaries obtain deductions of income taxes designed to fund the SUS. Therefore, the study investigated patterns of healthcare utilization and public expenditure due to the use of public healthcare by beneficiaries of health insurance between 2003 and 2019.

Operative technique: Endoscopic transnasal surgery for congenital meningoencephalocele of the anterior skull base.

Congenital meningoencephaloceles of the anterior skull base (ASB) are rare lesions that become evident during childhood and, if not properly diagnosed and treated, can be associated with severe complications. In the past, encephaloceles were treated exclusively with open surgical approaches, which, however, are associated with high complication rates. Recent years have seen the large-scale introduction of transnasal endoscopic approaches to the skull base, and several Authors suggest that endoscopic resection and repair in cases of meningoencephalocele may be the treatment of first choice, being associated with lower complication rates and reduced operative time compared with open procedures.

Gating residues govern ligand unbinding kinetics from the buried cavity in HIF-2α PAS-B.

While transcription factors have been generally perceived as "undruggable," an exception is the HIF-2 hypoxia-inducible transcription factor, which contains an internal cavity that is sufficiently large to accommodate a range of small-molecules, including the therapeutically used inhibitor belzutifan. Given the relatively long ligand residence times of these small molecules and the lack of any experimentally observed pathway connecting the cavity to solvent, there has been great interest in understanding how these drug ligands exit the buried receptor cavity. Here, we focus on the relevant PAS-B domain of hypoxia-inducible factor 2α (HIF-2α) and examine how one such small molecule (THS-017) exits from the buried cavity within this domain on the seconds-timescale using atomistic simulations and ZZ-exchange NMR.

Six-minute walk test as outcome measure of fatigability in adults with spinal muscular atrophy treated with nusinersen.

Introduction/aims: Fatigue (subjective perception) and fatigability (objective motor performance worsening) are relevant aspects of disability in individuals with spinal muscular atrophy (SMA). The effect of nusinersen on fatigability in SMA patients has been investigated with conflicting results. We aimed to evaluate this in adult with SMA3.

Combined Flow-Fluorescence in situ hybridization to HHV-8 and EBV reveals the viral heterogeneity of primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma associated with Kaposi Sarcoma-associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein-Barr virus (EBV) in 60-80% of cases. Tools allowing a reliable PEL diagnosis are lacking.

Identification of small-molecule ligand-binding sites on and in the ARNT PAS-B domain.

Transcription factors are challenging to target with small-molecule inhibitors due to their structural plasticity and lack of catalytic sites. Notable exceptions include naturally ligand-regulated transcription factors, including our prior work with the hypoxia-inducible factor (HIF)-2 transcription factor, showing that small-molecule binding within an internal pocket of the HIF-2α Per-Aryl hydrocarbon Receptor Nuclear Translocator (ARNT)-Sim (PAS)-B domain can disrupt its interactions with its dimerization partner, ARNT. Here, we explore the feasibility of targeting small molecules to the analogous ARNT PAS-B domain itself, potentially opening a promising route to modulate several ARNT-mediated signaling pathways.

Exercise training for patients with heart failure and preserved ejection fraction. A narrative review.

Heart failure with preserved ejection fraction (HFpEF) remains a significant global health challenge, accounting for up to 50% of all heart failure cases and predominantly affecting the elderly and women. Despite advancements in therapeutic strategies, HFpEF's complexity poses substantial challenges in management, particularly due to its high comorbidity burden, including renal failure, atrial fibrillation, and obesity, among others. These comorbidities not only complicate the pathophysiology of HFpEF but also exacerbate its symptoms, necessitating a personalized approach to treatment focused on comorbidity management and symptom alleviation.

Cerebral vasomotor reactivity in the acute phase and after 6 months in non-disabling stroke/TIA: A prospective cohort study.

Background And Aim: Cerebral Vasomotor Reactivity (VMR) is a property of cerebral hemodynamics that protects from cerebrovascular disease. We aimed to explore the VMR longitudinal changes in patients with acute non-disabling stroke/Transient Ischemic Attack (TIA) to understand its implication in stroke ethiopatogenesis.

Methods: VMR by Transcranial Doppler Breath Holding test was performed at 48-72 h from stroke onset (T1) and after 6 months (T2) on MCA of the non-affected hemisphere and PCA of the affected hemisphere.

Neural stem/progenitor cells from olfactory neuroepithelium collected by nasal brushing as a cell model reflecting molecular and cellular dysfunctions in schizophrenia.

Objectives: Neural stem/progenitor cells derived from olfactory neuroepithelium (hereafter olfactory neural stem/progenitor cells, ONSPCs) are emerging as a potential tool in the exploration of psychiatric disorders. The present study intended to assess whether ONSPCs could help discern individuals with schizophrenia (SZ) from non-schizophrenic (NS) subjects by exploring specific cellular and molecular features.

Methods: ONSPCs were collected from 19 in-patients diagnosed with SZ and 31 NS individuals and propagated in basal medium.

Maternal cardiovascular profile is altered in the preclinical phase of normotensive early and late intrauterine growth restriction.

Background: The maternal cardiovascular profile of patients who develop late fetal growth restriction has yet to be well characterized, however, a subclinical impairment in maternal hemodynamics and cardiac function may be present before pregnancy and may become evident because of the hemodynamic alterations associated with pregnancy.

Objective: This study aimed to investigate if maternal hemodynamics and the cardiovascular profile might be different in the preclinical stages (22-24 weeks' gestation) in cases of early and late fetal growth restriction in normotensive patients.

Study Design: This was a prospective echocardiographic study of 1152 normotensive nulliparous pregnant women at 22 to 24 weeks' gestation.

New insights into genetic diversity, and its influence on parasite biology and clinical outcomes.

Chagas disease, caused by , remains a serious public health problem worldwide. The parasite was subdivided into six distinct genetic groups, called "discrete typing units" (DTUs), from TcI to TcVI. Several studies have indicated that the heterogeneity of species directly affects the diversity of clinical manifestations of Chagas disease, control, diagnosis performance, and susceptibility to treatment.

A profile of azetukalner for the treatment of epilepsy: from pharmacology to potential for therapy.

Introduction: Epilepsies are a group of heterogeneous brain disorder, and antiseizure medications (ASMs) are the mainstay of treatment. Despite the availability of more than 30 drugs, at least one third of individuals with epilepsy are drug-resistant. This emphasizes the need for novel compounds that combine efficacy with improved tolerability.

Physiopathology and Treatment of Obesity and Overweight: A Proposal for a New Anorectic.

The "new epidemic," as WHO calls obesity, is caused by overeating, which, having exceeded the body's actual needs, accumulates in the form of health-damaging fat deposits. Moving more and eating less is the main remedy, but eating belongs to vital instincts, which are beyond the control of reason. In this sense, eating is different from drinking and breathing because without food it is possible to survive for a few weeks, without water for a few days, without oxygen for a few minutes.

Effects of prophylactic drug therapies and anti-calcitonin peptide-related monoclonal antibodies on subjective sleep quality: An Italian multicenter study.

Objective/background: sleep alterations strongly influence migraine severity. Prophylactic therapies have a major impact on migraine frequency and associated symptoms. The study purpose was to compare the impact of oral drug therapies or gene-related anti-calcitonin monoclonal antibodies (anti-CGRP mAbs) on sleep alterations.

Why selective screening for asymptomatic carotid stenosis is currently appropriate: a special report.

Introduction: Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program.

Impact of carotid stenosis on the outcome of stroke patients submitted to reperfusion treatments: a narrative review.

Intravenous thrombolysis (IT) and mechanical thrombectomy (MD) are the two interventional approaches that have changed the outcome of patients with acute ischemic stroke (AIS). Ipsilateral and contralateral carotid stenosis (ICS, CCS) play an important role in regulating cerebral hemodynamics, both in chronic and acute situations such as AIS. Several studies have explored their role in the incidence and severity of stroke, but very few have investigated the possible impact of ICS and CCS on the efficacy of interventional procedures.

Point-Of-Care low-field MRI in acute Stroke (POCS): protocol for a multicentric prospective open-label study evaluating diagnostic accuracy.

Introduction: Fast and accurate diagnosis of acute stroke is crucial to timely initiate reperfusion therapies. Conventional high-field (HF) MRI yields the highest accuracy in discriminating early ischaemia from haemorrhages and mimics. Rapid access to HF-MRI is often limited by contraindications or unavailability.

Identification of Small Molecule Ligand Binding Sites On and In the ARNT PAS-B Domain.

Transcription factors are generally challenging to target with small molecule inhibitors due to their structural plasticity and lack of catalytic sites. Notable exceptions include several naturally ligand-regulated transcription factors, including our prior work with the heterodimeric HIF-2 transcription factor which showed that small molecule binding within an internal pocket of the HIF-2α PAS-B domain can disrupt its interactions with its dimerization partner, ARNT. Here, we explore the feasibility of similarly targeting small molecules to the analogous ARNT PAS-B domain itself, potentially opening a promising route to simultaneously modulate several ARNT-mediated signaling pathways.

Respiratory function in a large cohort of treatment-naïve adult spinal muscular atrophy patients: a cross-sectional study.

Due to poor data in literature, we aimed to investigate the respiratory function in a large cohort of naïve Italian adult (≥18 years) SMA patients in a multi-centric cross-sectional study. The following respiratory parameters were considered: forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and need for non-invasive ventilation (NIV). We included 145 treatment-naïve adult patients (SMA2=18, SMA3=125; SMA4=2), 58 females (40 %), with median age at evaluation of 37 years (range 18-72).

An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

Objective: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear.

Methods: Fourteen controversial topics were identified.

NO donors on top of anti-hypertensive therapy reduces complications in chronic hypertensive pregnancies with hypodynamic circulation.

Objectives: Chronic hypertension is associated with significant adverse maternal and fetal outcomes that appear to be often associated to a hypodynamic circulation. Treatment of hypertensive disorders of pregnancy tailored on maternal hemodynamics might reduce or mitigate these complications. Our purpose was to assess the hemodynamic modifications induced by the addition of NO donors and increased oral fluid intake on top of standard antihypertensive therapy in hypodynamic chronic hypertensive patients.