Erratum to the development of uniportal video-assisted thoracoscopic surgery in São Paulo: from diagnosis to lobectomy.

[This corrects the article DOI: 10.21037/jtd.2016.10.79.].

The development of uniportal video-assisted thoracoscopic surgery in São Paulo: from diagnosis to lobectomy.

BACKGROUND: The use of uniportal video-assisted thoracoscopic surgery (VATS) has been increasing worldwide. Our main goal was to describe the evolution of uniportal surgery in the biggest private hospital in Latin America that is located in São Paulo, Brazil. METHODS: This descriptive and retrospective study included patients who underwent uniportal VATS in the thoracic surgical department of Beneficencia Portuguesa Hospital, after being referred to our team to undergo the aforementioned procedure within the period from February 2012 to March 2016. Postoperative management and results were analyzed. RESULTS: In the thoracic surgical department of Beneficencia Portuguesa Hospital, 454 uniportal VATS surgeries were performed. Of the patients, 287 (65.52%) were male and 151 (34.48%) were female, with a mean age of 57.48±23.4 years. In December 2015, we initiated anatomical pulmonary resections (lobectomies and segmentectomies). In the cases of uniportal lobectomies for lung cancer in the initial staging, lymphadenectomy was performed in all the patients, of whom 59 (87%) had at least seven lymph nodes included in the dissection and confirmed in the pathological anatomy report. Four of the uniportal lobectomy cases were converted to thoracotomy because of bleeding. One patient needed blood transfusion and vasoactive drug administration in the intensive care unit (ICU), and seven patients required pleural procedures (thoracentesis or pigtail catheter) after drainage removal. No operative or perioperative mortality related to the procedure occurred. The main hospital stay was 7.4±4.3 days. CONCLUSIONS: The uniportal thoracic procedures performed by our surgical team in São Paulo represent a breakthrough in the surgical treatment of thoracic pathologies in Southeast Brazil and can be offered as a safe and first-choice VATS procedure in our institution.

Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.

Cerebral deposition of amyloid beta peptide (Abeta) is an early and critical feature of Alzheimer's disease. Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of beta-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of beta-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as beta-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.

[Demographic and socioeconomic characteristics of patients from psychiatric hospitals in the city of Rio de Janeiro]. / Perfil demográfico e sócio-econômico da população de internos dos hospitais psiquiãtricos da cidade do Rio de Janeiro.

Knowledge on the characteristics of patients admitted to psychiatric hospitals is essential to adequate care, yet such information is not always available. A survey was conducted on patients in the 20 psychiatric hospitals in the city of Rio de Janeiro, Brazil. This paper presents demographic and socioeconomic data on the study population: 3223 persons (66.0% male; 52.6% under 40) on October 24, 1995. 73.8% had not finished elementary school; 25.5% were illiterate. 71.6% of the males and 61.1% of the females were single. Both groups had the same divorce percentage (13%). 43.1% of patients had jobs at the time of first admission, but only half had kept them by the time of this survey. Some 50% of the patients only received visits at extended intervals or not at all. This finding, plus the fact that 37.4% had been hospitalized for more than one year and 65. 1% did not leave the hospital during holidays or weekends, provides a picture of their social isolation. The findings are discussed based on epidemiological data, and hypotheses are suggested to explain some of the results.

Oligomerization of endogenous and synthetic amyloid beta-protein at nanomolar levels in cell culture and stabilization of monomer by Congo red.

Amyloid beta-proteins (A beta) are proteolytic fragments of the beta-amyloid precursor protein (beta APP) that are secreted by mammalian cells throughout life but also accumulate progressively as insoluble cerebral aggregates in Alzheimer's disease (AD). Because mounting evidence indicates that A beta aggregation and deposition are early, critical features of AD leading to neurotoxicity, many studies of A beta aggregation have been conducted using synthetic peptides under generally nonphysiological conditions and concentrations. We recently described the oligomerization of A beta peptides secreted by beta APP-expressing cells at low nanomolar (20-30 ng/mL) levels into sodium dodecyl sulfate- (SDS-) stable oligomers of 6-16 kDa. Here, we extensively characterize this in vitro system and show that the amyloid binding dye, Congo red, acts to markedly decrease oligomer/monomer ratios by stabilizing the 4 kDa A beta monomers (ID50 approximately equal to 3.4 microM). Addition of radioiodinated synthetic A beta 1-40 to the cultures or to their conditioned media at physiological concentrations (0.25-2.5 nM) reveals that it undergoes progressive aggregation into SDS-stable oligomers of 6-25 kDa during brief (approximately 4 h) incubation at 37 degrees C, and this is inhibitable by Congo red. The level of A beta oligomers can be quantitated in the Chinese hamster ovary (CHO) conditioned medium by size-exclusion chromatography as well as by SDS-polyacrylamide gel electrophoresis (PAGE), and comparison of these two methods suggests that aggregation of A beta into higher molecular weight polymers that are not detectable by SDS-PAGE occurs in the cultures. We conclude that both endogenous and synthetic A beta can assemble into stable oligomers at physiological concentrations in cell culture, providing a manipulable system for studying the mechanism of early A beta aggregation and identifying inhibitors thereof under biologically relevant conditions.

Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue.

Humans inheriting missense mutations in the presenilin (PS)1 and -2 genes undergo progressive cerebral deposition of the amyloid beta-protein at an early age and develop a clinically and pathologically severe form of familial Alzheimer's disease (FAD). Because PS1 mutations cause the most aggressive known form of AD, it is important to elucidate the structure and function of this multitransmembrane protein in the brain. Using a panel of region-specific PS antibodies, we characterized the presenilin polypeptides in mammalian tissues, including brains of normal, AD, and PS1-linked FAD subjects, and in transfected and nontransfected cell lines. Very little full-length PS1 or -2 was detected in brain and untransfected cells; instead the protein occurred as a heterogeneous array of stable N- and C-terminal proteolytic fragments that differed subtly among cell types and mammalian tissues. Sequencing of the major C-terminal fragment from PS1-transfected human 293 cells showed that the principal endoproteolytic cleavage occurs at and near Met298 in the proximal portion of the large hydrophilic loop. Full-length PS1 in these cells is quickly turned over (T1/2 approximately 60 min), in part to the two major fragments. The sizes and amounts of the PS fragments were not significantly altered in four FAD brains with the Cys410Tyr PS1 missense mutation. Our results indicate that presenilins are rapidly processed to N- and C-terminal fragments in both neural and nonneural cells and that interference with this processing is not an obligatory feature of FAD-causing mutations.

[New subjects; new rights: the debate about the psychiatric in Brazil]. / Novos sujeitos, novos direitos: o debate em torno da reforma psiquiátrica.

The author analysis and talks about the discussion of the process of Brazilian Psychiatric Reform and Paulo Delgado's legislation, which proposes new technologies in mental health care that substitutes the psychiatric hospital. To the author, the concept of de-institutionalization in opposition to desospitalization, defines better the ethics aspects in mental health care.

[An adventure in the insane asylum: the life of Franco Basaglia]. / Uma aventura no manicômio: a trajetória de Franco Basaglia.

The process of change in the mental health field and psychiatric reforms bear a close relationship to practical and theoretical issues stemming from Franco Basaglia's experience. This article is intended as a reflection on Basaglia's career, stressing the main concepts and theoretical references he worked with and seeking to trace the unique nature of his contributions to the current project for de-institutionalizing psychiatry. Basaglia produces a break by profoundly challenging psychiatric knowledge and institutions, thus allowing for a new epistemological framework (a framework that was thus also new in relation to culture and mental health care) in dealing with insanity. Based on the observation that Basaglia's work is little known, this article attempts to revisit his thinking, highlighting the unique nature of his contributions and stressing the need for a better understanding of his work by those who are devoted to the field of mental health and social institutions.

Temporal effects of thrombolytic agents on platelet function in vivo and their modulation by prostaglandins.

To examine the temporal effects of plasmin generated in vivo on platelet function, we infused tissue-type plasminogen activator (t-PA) in rabbits over 3 hours and measured ex vivo platelet aggregation. We noted an initial increase in the aggregation response to ADP occurring 30 minutes after the start of infusion. This enhanced response was short-lived and by 180 minutes was reduced, compared with pretreatment levels. Baseline aggregation response was restored by 240 minutes. This pattern of aggregation response to t-PA infusion was also seen with thrombin as the agonist. Coinfusion of either prostaglandin I2 or prostaglandin E1 abolished the initial hyperaggregable phase induced by t-PA; the hypoaggregable phase occurred earlier (after 60 minutes) and persisted throughout the 1-hour recovery period. Similarly, streptokinase infused for 1 hour also increased platelet aggregation at early times and then reduced aggregation responses after the first hour. Plasma plasmin activity increased as expected with t-PA infusion alone, peaking at 30 minutes and returning to baseline by the first hour. Interestingly, prostaglandin E1 blunted the rise in plasma plasmin activity. This same dose of prostaglandin E1 or prostaglandin I2 used alone did not appreciably alter platelet function at any time during the experiment. Our data show that therapeutic doses of t-PA or streptokinase produce a biphasic effect on platelet aggregation response in the rabbit. Coinfusion of either of the antiplatelet agents, prostaglandin E1 or prostaglandin I2, abolishes the hyperaggregable phase and prolongs the inhibitory effects on platelet aggregation produced by t-PA. These data suggest that the effects of thrombolytic agents on platelet function are complex and can be modulated by antiplatelet prostaglandins.

Plasma membrane enrichment with cis-unsaturated fatty acids enhances LDL metabolism in U937 monocytes.

The mechanism by which dietary cis-unsaturated fatty acids lower low density lipoprotein (LDL) cholesterol is unknown. Because cis-unsaturated fatty acids incorporated into cell membranes increase membrane fluidity and, as a result, can alter membrane-dependent cell functions, we examined LDL binding, uptake, and degradation in upregulated U937 monocytes enriched in membrane oleate, a monounsaturated fatty acid, and membrane linoleate, a polyunsaturated fatty acid. The same parameters were also examined in upregulated U937 monocytes enriched in membrane stearate, a saturated fatty acid, and in upregulated, unmodified U937 monocytes. Monocytes enriched in cis-unsaturated fatty acids exhibited augmented LDL binding, internalization, and degradation compared with both stearate-enriched monocytes and unmodified monocytes. The molar potency of linoleate in augmenting LDL metabolism was 50% greater than that of oleate. Enrichment with oleate and linoleate resulted in a decrease in the fatty acyl mole-weighted melting point of the plasma membrane and an increase in plasma membrane fluidity, as indicated by a reduction in the steady-state fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene incorporated into the membrane. Stearate-enriched monocytes exhibited a slight increase in the plasma membrane fatty acyl mole-weighted melting point and essentially no change in plasma membrane fluidity. Thus, one mechanism by which cis-unsaturated fatty acids lower LDL cholesterol may involve alteration in membrane lipid composition and physical properties, thereby leading to an increase in cellular clearance of this atherogenic lipoprotein.

N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.

Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor and 2) this effect is associated with increasing intracellular platelet cyclic GMP levels.