Prevalence of Critical Congenital Heart Disease Detected in the Pulse Oximetry Test in Asymptomatic Newborns, ≥35 Gestational Weeks, in a Maternity in Southern Brazil

Abstract Background Congenital heart diseases (CHD) are one of the most prevalent malformations, and the screening tests to identify critical congenital heart disease (CCHD) is the pulse oximetry test, with subsequent investigation and treatment. Objective To quantify positive pulse oximetry tests and verify the prevalence of CCHD detected by it in asymptomatic newborns, ≥35 gestational weeks, in a Brazilian maternity hospital. Methodology This is an observational, retrospective, quantitative, analytical and cross-sectional study, conducted from October 2020 to May 2022, in a maternity hospital in southern Brazil, through the collection of records of positive oximetry pulse tests, following the norms of screening CCHD test of the Brazilian Society of Pediatrics (SBP), after they were evaluated with echocardiography for confirmation or exclusion of CHD. Results A total of 5,667 newborns were evaluated in this study, according to the inclusion criteria; 0.17% (n = 10) had a positive pulse oximetry test. Regarding the results of the echocardiography of the neonates with a positive test, two were normal, seven were cases of patent foramen ovale (PFO), and one was a case (0,017%) with interatrial communication (IAC) diagnosis. In the same period, five neonates with CCHD were born, symptomatic, diagnosed by physical examination, and referred to neonatal intensive care units (NICU) before taking the neonatal cardiac screening (< 24 hours of life). Conclusion The prevalence of positive pulse oximetry tests was 0.17% and none CCHD was detected. Five cases of CCHD were born in this period, but they were diagnosed before the recommend time to perform the screening test.

Prevalence of depressive disorder in the adult population of Latin America: a systematic review and meta-analysis.

Background: Depressive disorder is one of the leading causes of disability worldwide; however its prevalence and association with inequality and crime is poorly characterised in Latin America. This study aimed to: i. systematically review population-based studies of prevalence of ICD/DSM depressive disorder in Latin America, ii. report pooled regional, country, and sex-specific prevalence estimates, and iii. test its association with four country-level development indicators: human development (HDI), income (Gini) and gender inequality (GII), and intentional homicide rate (IHR). Methods: We conducted a systematic review and meta-analysis of population-based studies reporting primary data on the prevalence of ICD/DSM depressive disorder in Latin America from 1990 to 2023, irrespective of language. We searched PubMed, PsycINFO, Cochrane Library, SciELO (regional database), LILAC (regional database), and available grey literature. Study quality was assessed using JBI's critical appraisal tools. We generated pooled estimates using random-effects meta-analysis; heterogeneity was assessed using the I2 statistic. Meta-regression analyses were used to test associations of depression prevalence with indicators of inequality and human development. The study was registered with PROSPERO (CRD42019143054). Findings: Using data from 40 studies in Latin America, lifetime, 12-month, and current prevalence of ICD/DSM depressive disorder were calculated at 12.58% (95% CI 11.00%-14.16%); 5.30% (4.55-6.06%), and 3.12% (2.22-4.03), respectively. Heterogeneity was high across lifetime, 12-month, and current prevalence, sex, and countries. 12-month and current prevalence was associated with higher Gini and GII, 12-month prevalence with lower HDI, and current prevalence with higher IHR. Interpretation: We found a high prevalence of ICD/DSM depressive disorders in Latin America, and a statistically significant association with inequality and development indicators. The high heterogeneity found across prevalence periods and the major gaps in country representation underscore the need to escalate efforts to improve mental health access and research capabilities in Latin America. Systematic, comparable prevalence estimates would inform more effective decision-making in the region. Funding: Pfizer Independent Medical Education Grant.

The Validity and Reliability of the PHQ-9 and PHQ-2 on Screening for Major Depression in Spanish Speaking Immigrants in Chile: A Cross-Sectional Study.

BACKGROUND: The study aimed to explore the psychometric properties of two versions of the Patient Health Questionnaires (PHQ-9 and PHQ-2) on screening for Major Depressive Disorder (MDD) among Spanish-speaking Latin American adult immigrants in Santiago, and to explore factors associated with a higher risk of occurrence of MDD among them. METHODS: A representative sample of 897 Spanish-speaking immigrants completed the PHQ-9. The Composite International Diagnostic Interview (CIDI) was employed to evaluate MDD. Internal consistency and structural validity were evaluated using Cronbach's α coefficient and confirmatory factor analysis (CFA). Convergent validity with the 7-item General Anxiety Disorder Scale (GAD-7) was assessed using Spearman's correlations. Sensitivity, specificity, positive predictive values, and area under the receiver operating characteristic (ROC) curve were calculated for different cut-off points. Logistic regression analysis was used to identify factors associated with the risk of MDD. RESULTS: Cronbach's α coefficient of the PHQ-9 was 0.90; item-total correlation coefficients ranged from 0.61 to 0.76 and correlation with the GAD-7 was moderate (r = 0.625; p < 0.001). CFA on three alternative models suggests a plausible fit in the overall sample and among two of the subsamples: Peruvians and Venezuelans. Taking the results of CIDI as the gold standard for MDD, the area under the ROC curve was 0.91 (95% confidence interval (CI): 0.83~1.0). When the cut-off score was equal to 5, values of sensitivity, specificity, and Youden's index were 0.85, 0.90, and 0.75, respectively. Multivariate logistic regression analyses showed that the influence of having three or more children (OR = 3.91, 95% CI: 1.20~12.81; p < 0.05), residency in Chile of up to three years (OR = 1.79, 95% CI: 1.07~3.00; p < 0.05), active debt (OR = 2.74, 95% CI: 1.60~4.70; p < 0.001), a one (OR = 2.01, 95% CI: 1.03~3.94; p < 0.05) and two or more events of adversity during childhood (OR = 5.25, 95% CI: 1.93~14.3; p < 0.01) on the occurrence of MDD was statistically significant. Reliability (α = 0.62), convergent (r = 0.534; p < 0.01) and criterion (AUC = 0.85, 95% CI: 0.67~1.00) validity coefficients of the PHQ-2 were weaker than for the PHQ-9. CONCLUSIONS: The PHQ-2 and the PHQ-9 are reliable and valid instruments for use as screeners for MDD among Spanish-speaking populations of Latin America.

Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease that leads to motor impairment due to a chronic inflammatory process in the central nervous system (CNS). However, the HAM/TSP pathogenesis is not completely clear, and biomarkers to define the disease prognosis are still necessary. Thus, we aimed to identify biomarkers for HAM/TSP and potential mechanisms involved in disease development. To that end, the concentrations of VILIP-1, BDNF, VEGF, ß-NGF, TGF-ß1, fractalkine/CX3CL1, IL-6, IL-18, and TNF-α, and the soluble forms of TREM-1, TREM-2, and RAGE, were assessed using a multiplex bead-based immunoassay in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n = 20), asymptomatic HTLV-1 carriers (AC) (n = 13), and HTLV-1-seronegative individuals (n = 9), with the results analyzed according to the speed of HAM/TSP progression. HAM/TSP patients had elevated fractalkine in the serum but not in the CSF, particularly those with low neuroinflammatory activity (CSF/serum ratio of neopterin <1 and of CXCL10 < 2). HAM/TSP patients with normal CSF levels of neurofilament light chain (NfL) showed elevated ß-NGF in serum, and serum BDNF levels were increased in HTLV-1-infected individuals, particularly in HTLV-1 AC. Both HTLV-1 AC and HAM/TSP patients had lower TGF-ß1 levels in CSF compared to uninfected individuals, and HAM/TSP patients with active CNS inflammation showed higher CSF levels of IL-18, which correlated with markers of inflammation, neuronal death, and blood−brain-barrier permeability. Although none of the factors evaluated were associated with the speed of HAM/TSP progression, reduced TGF-ß1 levels in CSF suggest that suppressive responses to control subclinical and/or active neurodegeneration are impaired, while increased CSF IL-18 indicates the involvement of inflammasome-mediated mechanisms in HAM/TSP development.

Bone Marrow Stromal Cell Regeneration Profile in Treated B-Cell Precursor Acute Lymphoblastic Leukemia Patients: Association with MRD Status and Patient Outcome.

For the last two decades, measurable residual disease (MRD) has become one of the most powerful independent prognostic factors in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the effect of therapy on the bone marrow (BM) microenvironment and its potential relationship with the MRD status and disease free survival (DFS) still remain to be investigated. Here we analyzed the distribution of mesenchymal stem cells (MSC) and endothelial cells (EC) in the BM of treated BCP-ALL patients, and its relationship with the BM MRD status and patient outcome. For this purpose, the BM MRD status and EC/MSC regeneration profile were analyzed by multiparameter flow cytometry (MFC) in 16 control BM (10 children; 6 adults) and 1204 BM samples from 347 children and 100 adult BCP-ALL patients studied at diagnosis (129 children; 100 adults) and follow-up (824 childhood samples; 151 adult samples). Patients were grouped into a discovery cohort (116 pediatric BCP-ALL patients; 338 samples) and two validation cohorts (74 pediatric BCP-ALL, 211 samples; and 74 adult BCP-ALL patients; 134 samples). Stromal cells (i.e., EC and MSC) were detected at relatively low frequencies in all control BM (16/16; 100%) and in most BCP-ALL follow-up samples (874/975; 90%), while they were undetected in BCP-ALL BM at diagnosis. In control BM samples, the overall percentage of EC plus MSC was higher in children than adults (p = 0.011), but with a similar EC/MSC ratio in both groups. According to the MRD status similar frequencies of both types of BM stromal cells were detected in BCP-ALL BM studied at different time points during the follow-up. Univariate analysis (including all relevant prognostic factors together with the percentage of stromal cells) performed in the discovery cohort was used to select covariates for a multivariate Cox regression model for predicting patient DFS. Of note, an increased percentage of EC (>32%) within the BCP-ALL BM stromal cell compartment at day +78 of therapy emerged as an independent unfavorable prognostic factor for DFS in childhood BCP-ALL in the discovery cohort­hazard ratio (95% confidence interval) of 2.50 (1−9.66); p = 0.05­together with the BM MRD status (p = 0.031). Further investigation of the predictive value of the combination of these two variables (%EC within stromal cells and MRD status at day +78) allowed classification of BCP-ALL into three risk groups with median DFS of: 3.9, 3.1 and 1.1 years, respectively (p = 0.001). These results were confirmed in two validation cohorts of childhood BCP-ALL (n = 74) (p = 0.001) and adult BCP-ALL (n = 40) (p = 0.004) treated at different centers. In summary, our findings suggest that an imbalanced EC/MSC ratio in BM at day +78 of therapy is associated with a shorter DFS of BCP-ALL patients, independently of their MRD status. Further prospective studies are needed to better understand the pathogenic mechanisms involved.

Does Arterialization of Portal Vein Have Any Effects in Large-for-Size Liver Transplantation? Hemodynamic, Histological, and Biomolecular Experimental Studies.

BACKGROUND: In pediatric liver transplantation, the optimal size of the transplanted liver ranges between 0.8% and 4.0% of the recipient's weight. Sometimes, the graft weight exceeds this upper limit, characterizing the large-for-size condition potentially associated with reduced blood flow and worsening of ischemia-reperfusion injury. Therefore, it would be beneficial to increase the portal flow through arterialization of the portal vein. Materials and methods: Fifteen pigs underwent large-for-size liver transplants. They were divided into two groups: control (CTRL 6 animals - conventional technique) and arterialization - a shunt was established between the portal vein and the splenic artery (ART 9 animals). Hemodynamic, biochemical, histological, and molecular variables were compared. Results: Arterialization resulted in a significant increase in portal vein pressure but no changes in other hemodynamic variables, as shown in the analysis of variance. It was observed lower ALT values (p = 0.007), with no differences regarding the values of blood pH and lactate (p = 0.54 and p = 0.699 respectively) or histological variables (edema, steatosis, inflammation, necrosis, and IRI - p = 1.0, p = 0.943, p = 0.174, p = 0.832, p = 0.662, respectively). The molecular studies showed significantly increased expression of IL6 after 3 hours of reperfusion (p = 0.048) and decreased expression of ICAM immediately after reperfusion (p = 0.03). The regression analysis suggested a positive influence of portal flow and pressure on biochemical parameters. Conclusion: Arterialization of the portal vein showed no histological, biochemical, or molecular benefits in large-for-size transplantation.

Ih blockade reduces cocaine-induced firing patterns of putative dopaminergic neurons of the ventral tegmental area in the anesthetized rat.

The hyperpolarization-activated cation current (Ih) is a determinant of intrinsic excitability in various cells, including dopaminergic neurons (DA) of the ventral tegmental area (VTA). In contrast to other cellular conductances, Ih is activated by hyperpolarization negative to -55 mV and activating Ih produces a time-dependent depolarizing current. Our laboratory demonstrated that cocaine sensitization, a chronic cocaine behavioral model, significantly reduces Ih amplitude in VTA DA neurons. Despite this reduction in Ih, the spontaneous firing of VTA DA cells after cocaine sensitization remained similar to control groups. Although the role of Ih in controlling VTA DA excitability is still poorly understood, our hypothesis is that Ih reduction could play a role of a homeostatic controller compensating for cocaine-induced change in excitability. Using in vivo single-unit extracellular electrophysiology in isoflurane anesthetized rats, we explored the contribution of Ih on spontaneous firing patterns of VTA DA neurons. A key feature of spontaneous excitability is bursting activity; bursting is defined as trains of two or more spikes occurring within a short interval and followed by a prolonged period of inactivity. Burst activity increases the reliability of information transfer. To elucidate the contribution of Ih to spontaneous firing patterns of VTA DA neurons, we locally infused an Ih blocker (ZD 7288, 8.3 µM) and evaluated its effect. Ih blockade significantly reduced firing rate, bursting frequency, and percent of spikes within a burst. In addition, Ih blockade significantly reduced acute cocaine-induced spontaneous firing rate, bursting frequency, and percent of spikes within a burst. Using whole-cell patch-clamp, we determine the progressive reduction of Ih after acute and chronic cocaine administration (15 mg/k.g intraperitoneally). Our data show a significant reduction (~25%) in Ih amplitude after 24 but not 2 h of acute cocaine administration. These results suggest that a progressive reduction of Ih could serve as a homeostatic regulator of cocaine-induced spontaneous firing patterns related to VTA DA excitability.

Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression.

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease due to axonal damage of the corticospinal secondary to an inflammatory response against infected T-cells. In the present work, we aimed to evaluate biomarkers of neurodegeneration and neuroinflammation in the definition of HAM/TSP prognosis. Neurofilament light (NfL) and phosphorylated heavy (pNfH) chains, total Tau protein, cellular prion protein (PrPc), inflammatory chemokines, and neopterin were quantified in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n=21), HTLV-1 asymptomatic carriers (AC) (n=13), and HTLV-1 seronegative individuals with non-inflammatory non-degenerative neurological disease (normal-pressure hydrocephalus) (n=9) as a control group. HTLV-1 proviral load in peripheral blood mononuclear cells and the expression of chemokine receptors CCR4, CCR5, and CXCR3 in infected CD4+ T-cells (HTLV-1 Tax+ cells) were also assessed. CSF levels of Tau, NfL, and pNfH were similar between groups, but PrPc and neopterin were elevated in HAM/TSP patients. Most individuals in the control group and all HTLV-1 AC had CSF/serum neopterin ratio < 1.0, and two-thirds of HAM/TSP patients had ratio values > 1.0, which positively correlated with the speed of disease progression and pNfH levels, indicating active neuroinflammation. HAM/TSP patients showed high serum levels of CXCR3-binding chemokines (CXCL9, CXCL10, and CXCL11) and elevated CSF levels of CCL2, CCL3, CCL4, CCL17, CXCL5, CXCL10, and CXCL11. Indeed, CXCL10 concentration in CSF of HAM/TSP patients was 5.8-fold and 8.7-fold higher in than in HTLV-1 AC and controls, respectively, and correlated with CSF cell counts. HAM/TSP patients with typical/rapid disease progression had CSF/serum CXCL10 ratio > 1.0 and a higher frequency of CXCR3+Tax+CD4+ T-cells in blood, which indicated a positive gradient for the migration of infected cells and infiltration into the central nervous system. In conclusion, the slow progression of HAM/TSP abrogates the usefulness of biomarkers of neuronal injury for the disease prognosis. Thus, markers of inflammation provide stronger evidence for HAM/TSP progression, particularly the CSF/serum neopterin ratio, which may contribute to overcome differences between laboratory assays.

Weighted neurofeedback facilitates greater self-regulation of functional connectivity between the primary motor area and cerebellum.

Objective.Brain-computer interface (BCI) is a tool that can be used to train brain self-regulation and influence specific activity patterns, including functional connectivity, through neurofeedback. The functional connectivity of the primary motor area (M1) and cerebellum play a critical role in motor recovery after a brain injury, such as stroke. The objective of this study was to determine the feasibility of achieving control of the functional connectivity between M1 and the cerebellum in healthy subjects. Additionally, we aimed to compare the brain self-regulation of two different feedback modalities and their effects on motor performance.Approach.Nine subjects were trained with a real-time functional magnetic resonance imaging BCI system. Two groups were conformed: equal feedback group (EFG), which received neurofeedback that weighted the contribution of both regions of interest (ROIs) equally, and weighted feedback group (WFG) that weighted each ROI differentially (30% cerebellum; 70% M1). The magnitude of the brain activity induced by self-regulation was evaluated with the blood-oxygen-level-dependent (BOLD) percent change (BPC). Functional connectivity was assessed using temporal correlations between the BOLD signal of both ROIs. A finger-tapping task was included to evaluate the effect of brain self-regulation on motor performance.Main results.A comparison between the feedback modalities showed that WFG achieved significantly higher BPC in M1 than EFG. The functional connectivity between ROIs during up-regulation in WFG was significantly higher than EFG. In general, both groups showed better tapping speed in the third session compared to the first. For WFG, there were significant correlations between functional connectivity and tapping speed.Significance.The results show that it is possible to train healthy individuals to control M1-cerebellum functional connectivity with rtfMRI-BCI. Besides, it is also possible to use a weighted feedback approach to facilitate a higher activity of one region over another.

Selective Moonlighting Cell-Penetrating Peptides.

Cell penetrating peptides (CPPs) are molecules capable of passing through biological membranes. This capacity has been used to deliver impermeable molecules into cells, such as drugs and DNA probes, among others. However, the internalization of these peptides lacks specificity: CPPs internalize indistinctly on different cell types. Two major approaches have been described to address this problem: (i) targeting, in which a receptor-recognizing sequence is added to a CPP, and (ii) activation, where a non-active form of the CPP is activated once it interacts with cell target components. These strategies result in multifunctional peptides (i.e., penetrate and target recognition) that increase the CPP's length, the cost of synthesis and the likelihood to be degraded or become antigenic. In this work we describe the use of machine-learning methods to design short selective CPP; the reduction in size is accomplished by embedding two or more activities within a single CPP domain, hence we referred to these as moonlighting CPPs. We provide experimental evidence that these designed moonlighting peptides penetrate selectively in targeted cells and discuss areas of opportunity to improve in the design of these peptides.

Microfabrication with Very Low-Average Power of Green Light to Produce PDMS Microchips.

In this article, we show an alternative low-cost fabrication method to obtain poly(dimethyl siloxane) (PDMS) microfluidic devices. The proposed method allows the inscription of micron resolution channels on polystyrene (PS) surfaces, used as a mold for the wanted microchip's production, by applying a high absorption coating film on the PS surface to ablate it with a focused low-power visible laser. The method allows for obtaining micro-resolution channels at powers between 2 and 10 mW and can realize any two-dimensional polymeric devices. The effect of the main processing parameters on the channel's geometry is presented.

Inflammatory Cytokine Patterns Associated with Neurological Diseases in Coronavirus Disease 2019.

Patients with coronavirus disease 2019 (COVID-19) can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, chemokine (C-X-C motif) ligand 8 (CXCL8), and CXCL10 in the cerebrospinal fluid. Conversely, encephalopathy was associated with high serum levels of IL-6, CXCL8, and active tumor growth factor ß1. Inflammatory syndromes of the central nervous system in COVID-19 can appear early, as a parainfectious process without significant systemic involvement, or without direct evidence of severe acute respiratory syndrome coronavirus 2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines. ANN NEUROL 2021;89:1041-1045.

Percepções de pacientes adultos sobre a unidade de terapia intensiva / Perceptions of adult patients about the intensive therapy unit

Objetivo: Analisar e descrever as percepções sobre a unidade de terapia intensiva de pacientes adultos que estiveram internados na UTI de um Hospital Universitário de Belém do Pará. Metodologia: Estudo descritivo, exploratório de abordagem qualitativa, realizada com 10 pacientes que estiveram internados na UTI, no período de agosto a dezembro de 2017, através de entrevista semiestruturada e analisada pela técnica de análise de conteúdo. Resultados: Os depoimentos foram sintetizados em quatro unidades: "Percepção prévia e posterior da UTI: Risco de morte versus recuperação" "Alterações ambientais e de hábitos em UTI: agentes estressores"; "Percepção dos cuidados: aspectos favoráveis e desfavoráveis à humanização"; e "Memórias marcantes". Conclusão: Com este estudo foi possível observar as percepções prévias e posteriores a internação em unidade de terapia intensiva, assim como as percepções voltadas ao cuidado em saúde recebido e as principais memórias que marcaram a vida dos pacientes após a internação na UTI. (AU)

Objective: To analyze and describe the perceptions about the intensive care unit of adult patients who were hospitalized in the ICU of a University Hospital of Belém do Pará. Method: Descriptive, exploratory qualitative approach, carried out with 10 patients who were hospitalized in the ICU, from August to December 2017, through a semi-structured interview and analyzed by the content analysis technique. Results: The statements were synthesized in four units: "Prior and subsequent ICU perception: Death risk versus recovery" "Environmental changes and habits in ICU: stressors"; "Perception of care: aspects favorable and unfavorable to humanization"; and "Remarkable Memories". Conclusion: With this research it was possible to observe the previous and subsequent perceptions of hospitalization in an intensive care unit, as well as the perceptions regarding health care received and the main memories that marked the life of patients after ICU stay. (AU)

Objectivo: Analizar y describir las percepciones sobre la unidad de terapia intensiva de pacientes adultos que estuvieron internados en la UTI de un Hospital Universitario de Belém do Pará. Metodo: Investigación descriptiva, exploratoria de abordaje cualitativo, realizada con 10 pacientes que estuvieron internados en la UTI, en el período de agosto a diciembre de 2017, a través de entrevista semiestructurada y analizada por la técnica de análisis de contenido. Resultados: Los testimonios fueron sintetizados en cuatro unidades: "Percepción previa y posterior de la UTI: Riesgo de muerte versus recuperación" "Alteraciones ambientales y de hábitos en UTI: agentes estresores"; "Percepción de los cuidados: aspectos favorables y desfavorables a la humanización"; y "Memorias marcadas". Conclusión: Con esta investigación fue posible observar las percepciones previas y posteriores la internación en unidad de terapia intensiva, así como las percepciones volcadas al cuidado en salud recibido y las principales memorias que marcaron la vida de los pacientes después de la internación en la UTI. (AU)

Alpha-1 Adrenergic Receptors Modulate Glutamate and GABA Neurotransmission onto Ventral Tegmental Dopamine Neurons during Cocaine Sensitization.

The ventral tegmental area (VTA) plays an important role in the reward and motivational processes that facilitate the development of drug addiction. Presynaptic α1-AR activation modulates glutamate and Gamma-aminobutyric acid (GABA) release. This work elucidates the role of VTA presynaptic α1-ARs and their modulation on glutamatergic and GABAergic neurotransmission during cocaine sensitization. Excitatory and inhibitory currents (EPSCs and IPSCs) measured by a whole cell voltage clamp show that α1-ARs activation increases EPSCs amplitude after 1 day of cocaine treatment but not after 5 days of cocaine injections. The absence of a pharmacological response to an α1-ARs agonist highlights the desensitization of the receptor after repeated cocaine administration. The desensitization of α1-ARs persists after a 7-day withdrawal period. In contrast, the modulation of α1-ARs on GABA neurotransmission, shown by decreases in IPSCs' amplitude, is not affected by acute or chronic cocaine injections. Taken together, these data suggest that α1-ARs may enhance DA neuronal excitability after repeated cocaine administration through the reduction of GABA inhibition onto VTA dopamine (DA) neurons even in the absence of α1-ARs' function on glutamate release and protein kinase C (PKC) activation. α1-AR modulatory changes in cocaine sensitization increase our knowledge of the role of the noradrenergic system in cocaine addiction and may provide possible avenues for therapeutics.

Choroiditis in a HIV-infected patient with disseminated cryptococcal infection: A case report and literature review.

BACKGROUND: Ocular involvement in AIDS patients is a common event mainly caused by inflammation or infection. Despite the high prevalence rate of cryptococcosis in these individuals, ocular features have been occasionally described. CASE REPORT: A 20-year-old Brazilian female with HIV infection recently diagnosed was admitted with a respiratory profile presumptively diagnosed as Pneumocystis jirovecii pneumonia; an ophthalmologic exam suggested choroiditis by this agent as well. She was complaining of headaches and blurred vision which led to cryptococcal meningitis diagnosis by a CSF positive India ink stain and Cryptococcus neoformans positive culture. Despite therapy based on amphotericin B plus fluconazole, her clinical state progressively worsened and the patient died one week later. At necropsy, disseminated cryptococcal infection was evidenced in several organs including eyes, which presented bilateral chorioretinitis. CONCLUSIONS: Cryptococcal ocular involvement in AIDS patients has been occasionally proved among the cases already reported. Thus, the post mortem exam is still pivotal to improve the quality of the clinical diagnosis, especially in limited-resource settings.

Time management of Internal Medicine medicalresidents, São Paulo, Brasil.

INTRODUCTION: Medical Residency is a recognized form of professional qualification, but there are criticisms regarding the overload of work activities. Given the length of the daily and weekly workdays, residents develop practices that enable them to reconcile the Residency with their personal life. AIM: To describe time management strategies in the daily routine of Internal Medicine Medical Residents of a university hospital in São Paulo, Brasil. METHODS: Eight interviews were conducted with resident physicians of the second year, addressing aspects of personal and family life, theoretical study, practical activities, and work bonds. Content analysis was carried out using the MaxQDA software. RESULTS: Six thematic categories emerged from the reports: work organization at the Medical Residency; learning and/or professional activities; housing, financial planning, and household activities; time for leisure and interpersonal relationship; family planning/children; rest/sleep. DISCUSSION: Several strategies are adopted for time management: residing near the hospital, domestic activities helped by housekeepers, postponement of maternity leave, and social support centered on interacting with other residents. There are paid activities not associated with the Residency, which lead to reduced time for rest, study, and leisure, with a greater loss during work at night shifts. CONCLUSIONS: Residents experience a period of intense learning, which requires a high workload and complex work. The evaluation of the work organization of medical residents should include not only time for rest but also time management strategies for daily activities, which can reduce the negative outcomes associated with long working hours.

Avaliação da capacidade funcional de pacientes atendidos em um ambulatório perioperatório do Distrito Federal / Evaluation of the functional capacity of patients attended in a perioperative outpatient clinic of the Federal District / Evaluación de la capacidad funcional de pacientes atendidos en un ambulatorio perioperatorio del Distrito Federal

Objetivo: Identificar a capacidade funcional de pacientes atendidos no ambulatório de avaliação perioperatória do Hospital Regional do Gama (APA-HRG), no Distrito Federal, bem como estabelecer relação com as estratificações cardíacas utilizadas. Método: Estudo observacional, descritivo, retrospectivo, com coleta de dados dos registros nos prontuários das consultas pré-operatórias de 292 pacientes triados como alto risco, executadas por equipe de médicos anestesiologistas e enfermeiros, realizadas no APA-HRG no período de junho de 2014 a junho de 2016. Resultados: O perfil da amostra constituiu-se, em sua maioria, por indivíduos do gênero feminino (78,77%), maiores de 60 anos (48,35%), não obesos (69,44%), encaminhados principalmente pela clínica ginecológica (39,79%), diagnosticados com hipertensão arterial sistêmica (44,17%) e tabagistas (12,67%). A capacidade funcional foi classificada como excelente em 63,18% (>10 equivalentes metabólicos) dos pacientes. Foi constatada associação significativa entre os equivalentes metabólicos e as estratificações da American Society of Anesthesiologists, do Índice de Risco Cardíaco Revisado e da Classificação Funcional da New York Heart Association. Conclusão: A maioria dos prontuários analisados era de pacientes com excelente capacidade funcional, apresentando associação significativa com as estratificações estudadas.

Objective: To identify the functional capacity of patients attended at the perioperative evaluation outpatient clinic of the Regional Hospital of Gama (APA-HRG), Federal District, as well as establish relationship with the cardiac stratifications employed. Method: Observational, descriptive, retrospective study with data collection of records from preoperative consultations of 292 patients screened as high risk, performed by a team of medical anesthesiologists and nurses, performed in the APA-HRG in the period from June 2014 to June 2016. Results: The sample profile consisted, for the most part, of female subjects (78.77%), of over 60 years of age (48.35%), not obese (69.44%), referred mainly by the gynecological clinic (39.79%), diagnosed with systemic arterial hypertension (44.17%) and smokers (12.67%). Functional capacity was classified as excellent in 63.18% (>10 metabolic equivalents) of patients. There was a significant association between the metabolic equivalents and the stratification of the American Society of Anesthesiologists, the Revised Cardiac Risk Index and the Functional Classification of the New York Heart Association. Conclusion: Most of the charts analyzed were of patients with excellent functional capacity, presenting a significant association with the stratifications studied.

Objetivo: Identificar la capacidad funcional de pacientes atendidos en el ambulatorio de evaluación perioperatoria del Hospital Regional do Gama (APA-HRG), en el Distrito Federal, así como establecer relación con las estratificaciones cardíacas utilizadas. Método: Estudio observacional, descriptivo, retrospectivo, con colecta de datos de los registros en los historiales médicos de las consultas preoperatorias de 292 pacientes seleccionados como alto riesgo, ejecutadas por equipo de médicos anestesistas y enfermeros, realizadas en el APA-HRG en el período de junio de 2014 a junio de 2016. Resultados: El perfil de la muestra se constituye, en su mayoría, por individuos del género femenino (78,77%), mayores de 60 años (48,35%), no obesos (69,44%), encaminados principalmente por la clínica ginecológica (39,79%), diagnosticados con hipertensión arterial sistémica (44,17%) y tabaquistas (12,67%). La capacidad funcional fue clasificada como excelente en un 63,18% (>10 equivalentes metabólicos) de los pacientes. Fue constatada asociación significativa entre los equivalentes metabólicos y las estratificaciones de la American Society of Anesthesiologists, del Índice de Riesgo Cardíaco Revisado y de la Clasificación Funcional de la New York Heart Association. Conclusión: La mayoría de los historiales médicos analizados era de pacientes con excelente capacidad funcional, presentando asociación significativa con las estratificaciones estudiadas.

Time management of Internal Medicine medicalresidents, São Paulo, Brasil

SUMMARY INTRODUCTION Medical Residency is a recognized form of professional qualification, but there are criticisms regarding the overload of work activities. Given the length of the daily and weekly workdays, residents develop practices that enable them to reconcile the Residency with their personal life. AIM To describe time management strategies in the daily routine of Internal Medicine Medical Residents of a university hospital in São Paulo, Brasil. METHODS Eight interviews were conducted with resident physicians of the second year, addressing aspects of personal and family life, theoretical study, practical activities, and work bonds. Content analysis was carried out using the MaxQDA software. RESULTS Six thematic categories emerged from the reports: work organization at the Medical Residency; learning and/or professional activities; housing, financial planning, and household activities; time for leisure and interpersonal relationship; family planning/children; rest/sleep. DISCUSSION Several strategies are adopted for time management: residing near the hospital, domestic activities helped by housekeepers, postponement of maternity leave, and social support centered on interacting with other residents. There are paid activities not associated with the Residency, which lead to reduced time for rest, study, and leisure, with a greater loss during work at night shifts. CONCLUSIONS Residents experience a period of intense learning, which requires a high workload and complex work. The evaluation of the work organization of medical residents should include not only time for rest but also time management strategies for daily activities, which can reduce the negative outcomes associated with long working hours.

RESUMO INTRODUÇÃO A Residência Médica é uma forma reconhecida de capacitação profissional, mas há críticas em relação à sobrecarga de trabalho. Dada a extensão das jornadas de trabalho diária e semanal, os residentes desenvolvem práticas para poder conciliar a Residência com sua vida pessoal. OBJETIVOS Descrever estratégias de gestão do tempo no cotidiano de médicos residentes de Clínica Médica em hospital universitário de São Paulo, Brasil. MÉTODOS Realizadas oito entrevistas com médicos residentes do 2o ano, abordando aspectos da vida pessoal, familiar, estudo teórico, atividades práticas e vínculos de trabalho. Realizada análise de conteúdo com auxílio do programa MaxQDA. RESULTADOS Seis categorias temáticas emergiram dos relatos: organização do trabalho na Residência Médica; atividade para aprendizado ou atividade profissional?; moradia, planejamento financeiro e atividades domésticas; tempo para lazer e relacionamentos interpessoais; planejamento familiar∕filhos; repouso∕sono. DISCUSSÃO Diversas estratégias são adotadas para gestão do tempo: residir próximo ao hospital, auxílio das atividades domésticas por diaristas, adiamento da maternidade e apoio social centrado no convívio com outros residentes. Há realização de atividades remuneradas não vinculadas à Residência, o que leva à redução do tempo previsto para repouso, estudo e lazer, com maior prejuízo nos períodos de plantões noturnos. CONCLUSÕES Os residentes vivenciam um período de aprendizado intenso, mas que exige uma carga horária elevada e trabalho complexo. A avaliação da organização do trabalho de médicos residentes deve incluir não somente tempo para repouso, mas também estratégias de gestão do tempo para atividades cotidianas. Estas podem reduzir o prejuízo associado às longas jornadas de trabalho.

Phenotypic and functional changes in gamma delta T lymphocytes from HTLV-1 carriers.

Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic inflammatory disease that leads to gradual loss of motor movement as a result of the death of spinal cord cells through immune mediated mechanisms. The risk to develop HAM/TSP disease positively correlates with the magnitude of HTLV-1 proviral load. Gamma-delta T lymphocytes have been recognized as important players in a variety of infectious diseases. Therefore, we have investigated interactions between HTLV-1 infection and γδ T lymphocytes during HAM/TSP. Similar frequencies of total γδ T lymphocytes and their Vγ9δ2+ and Vγ9δ2neg subpopulations were observed in HAM/TSP patients. However, T lymphocytes obtained from HTLV-1 carriers displayed significantly higher rates of spontaneous proliferation and NKp30 expression when compared to cells from uninfected donors. In addition, an important decrease in the frequency of granzyme B+ γδ T lymphocytes (approximately 50%) was observed in HAM/TSP patients. Higher proportion of IFN-γ+ γδ T lymphocytes was found in HTLV-1-infected patients, which positively correlated with the HTLV-1 proviral load in peripheral blood mononuclear cells. Collectively, our data indicates that HTLV-1 infection leads to phenotypic and functional changes in the population of γδ T lymphocyte population, suggesting that HTLV-1 infection modulates functions associated to these cells, which might be involved in controlling the infection or in the development of HTLV-1-associated diseases.

Perfil clínico e epidemiológico de pacientes obesos de um serviço ambulatorial de avaliação perioperatória / Clinical and epidemiological profile of obese patients from a pre-operative outpatient evaluation clinic / Perfil clínico y epidemiológico de pacientes obesos de un servicio ambulatorio de evaluación perioperatoria

Objetivo: Descrever o perfil clínico e epidemiológico de pacientes obesos de um serviço ambulatorial de avaliação perioperatória, realizado por enfermeiros e anestesiologistas, baseado em estratificações e avaliações do risco cardíaco. Método: Estudo descritivo, retrospectivo, composto por dados de 292 pacientes consultados pelo serviço ambulatorial de avaliação perioperatória, em que 88 foram identificados com obesidade. Foram analisadas variáveis demográficas, antropométricas (por índice de massa corporal ­ IMC), clínicas e cardíacas pelo teste do χ2. Resultados: Entre os pacientes, 30% eram obesos, dos quais 91% eram do sexo feminino. Em relação à presença de comorbidades, 50% eram portadores de hipertensão arterial sistêmica (HAS) e 22% a tinham associada ao diabetes mellitus (DM). Foi verificada prevalência de ASA P2 (74%) e alto risco para tromboembolismo venoso (63%); em relação aos riscos cardíacos pelo ACP (American College of Cardiology/American Heart Association ­ ACP, modificado por Detsky), a maioria (74%) foi estratificada como risco intermediário. Conclusão: A significativa incidência de comorbidades constatada acusa a necessidade de utilizar estratégias multiprofissionais na assistência perioperatória, voltadas para a população obesa, sendo possível identificar vulnerabilidades e diminuir riscos aos quais o indivíduo está sujeito, ao submeter-se a procedimentos cirúrgicos.

Objective: To describe the clinical and epidemiological profile of obese patients from a pre-operative outpatient evaluation clinic, performed by nurses and anesthesiologists based on cardiac risk assessment and stratification. Method: A descriptive, retrospective study, consisting of 292 patients consulted in the pre- -operative outpatient evaluation clinic, in which 88 were identified as obese. Demographic, anthropometric (by body mass index - BMI), clinical and cardiac variables were analyzed using the χ2 test. Results: 30% of the patients were obese, of which 91% were female. Regarding the presence of comorbidities, 50% had systemic arterial hypertension (SAH) and 22% had diabetes mellitus (DM). A prevalence of ASA P2 (74%) and high risk for venous thromboembolism (63%) was verified; in relation to cardiac risks according to the ACC (American College of Cardiology / American Heart Association - AHA, modified by Detsky), the majority (74%) was stratified/classified as intermediate risk. Conclusion: The significant incidence of comorbidities confirmed the need to use multiprofessional strategies in perioperative care, aimed at the obese population, with the possibility of identifying vulnerabilities and reduce the risks to the individual when undergoing surgical procedures

Objetivo: Describir o perfil clínico e epidemiológico de pacientes obesos de un servicio ambulatorio de evaluación perioperatoria, realizado por enfermeros y anestesistas, basado en estratificaciones y evaluaciones del riesgo cardíaco. Método: Estudio descriptivo, retrospectivo, compuesto por datos de 292 pacientes consultados por el servicio ambulatorio de evaluación perioperatoria, en que 88 fueron identificados com obesidad. Fueron analizadas variables demográficas, antropométricas (por índice de masa corporal ­ IMC), clínicas y cardíacas por el test de χ2. Resultados: Entre los pacientes, un 30% era obeso, del cual un 91% era del sexo femenino. Con relación a la presencia de comorbilidades, un 50% era portador de hipertensión arterial sistémica (HAS) y un 22% la tenía asociada a la diabetes mellitus (DM). Fue verificada prevalencia de ASA P2 (74%) y alto riesgo para tromboembolismo venoso (63%); con relación a los riesgos cardíacos por el ACP (American College of Cardiology/American Heart Association ­ ACP, modificado por Detsky), la mayoría (74%) fue estratificada como riesgo intermediario. Conclusión: La significativa incidencia de comorbilidades constatada acusa la necesidad de utilizar estrategias multiprofesionales en la asistencia perioperatoria, volcadas para la población obesa, siendo posible identificar vulnerabilidades y disminuir riesgos a los cuales el individuo está sujeto, a someterse a procedimientos quirúrgicos