BUPROPION MISUSE BY NASAL INSUFFLATION WITH A FATAL OUTCOME: CASE REPORT AND REVIEW.

Bupropion is the only FDA - approved synthetic cathinone, with increasing popularity in clinical practice due to its wide range of action, and lack of sexual side effects. However, its stimulant effect similar to amphetamines has growing the concern regarding its recreational use.

Electroconvulsive Therapy Use in Psychiatric Hospitalizations in Portugal: A Nationwide Descriptive Study.

OBJECTIVES: The primary aim of this study was to describe a Portuguese nationwide epidemiological perspective on the use of electroconvulsive therapy (ECT) in hospitalized psychiatric patients. The secondary aims of the study were to characterize clinical and sociodemographic trends of hospitalized patients treated with ECT. METHODS: A retrospective-observational study was conducted using an administrative database gathering every registered Portuguese public hospital hospitalizations from 2008 to 2015. We selected all hospitalizations with a procedure code 94.27 (Other electroshock therapy) defined by the International Classification of Diseases version 9, Clinical Modification. Variables included birth date, sex, address, primary and secondary diagnoses, admission/discharge date, length of stay, and discharge status from each single hospitalization episode. We also calculated Portugal's inpatient ECT prevalence rate (iP%). RESULTS: There were a total of 879 registered hospitalizations with ECT within the 8-year period of this study. Most occurred in female patients (53.4%), belonging to the age group of 51 to 70 years old, with a mean age of 50.5 years. The median length of stay was 43.0 days with an interquartile range of 27.0 to 68.0. The most frequent primary diagnosis was major depressive disorder, recurrent episode, representing 19.6% of all hospitalizations. The iP% for the study period was 0.71%. CONCLUSIONS: In Portugal, most of the patients who received ECT were women above middle age, and depressive disorders were the most common indication. Portugal's iP% represents a low rate when compared with other European countries, which might indicate an underutilization of ECT in Portuguese psychiatric hospitals.

The Impact of COVID-19 Pandemic on Psychiatric Emergency Department Visits - A Descriptive Study.

The coronavirus disease 2019 pandemic (COVID-19) has an important direct and indirect impact on both physical and mental health. We aim to describe the impact of an emergency state period due to COVID-19 on psychiatric emergency department (ED) visits. We conducted a retrospective observational study analysing all emergency visits occurring at a metropolitan psychiatric ED between March 19th and May 2nd 2019 and 2020 (the beginning/end date of the emergency state which Portugal was under due to COVID-19). Data regarding age, sex, diagnoses, admission date, discharge destiny and status were collected. Diagnoses were classified using the International Classification of Diseases version 9, Clinical Modification (ICD-9-CM). There was a 52·2% decrease on the number of psychiatric emergency visits during the emergency state period (n2020 = 780 vs n2019 = 1633 episodes). The decrease on psychiatric ED visits was greater in the female sex and in the younger age groups. Episodes with a primary diagnosis of Mood disorders lead the decrease on psychiatric ED visits with 68·3% less episodes. Schizophrenia and other psychotic disorders was the diagnosis group with the smaller decline (9·8% decrease). COVID-19 emergency state period had an important impact on the number and characteristics of psychiatric ED visits, reinforcing the great indirect effects of COVID-19 on mental health.

Institutional strategies as a mechanism to rationalize the negative effects of the judicialization of access to medicine in Brazil.

BACKGROUND: Recently, the Executive Branch and Judiciary in Brazil increased spending due to larger numbers of lawsuits that forced the State to provide health goods and services. This phenomenon, known as health judicialization, has created challenges and required the Executive Branch and Judiciary to create institutional strategies such as technical chambers and departments to reduce the social, economic and political distortions caused by this phenomenon. This study aims to evaluate the effects of two institutional strategies deployed by a Brazilian municipality in order to cope with the economic, social and political distortions caused by the phenomenon of health judicialization regarding access to medicines. METHODS: A longitudinal study was carried out in a capital in the Central-West Region of Brazil. A sample of 511 lawsuits was analyzed. The variables were placed into three groups: the sociodemographic characteristics and the plaintiffs' disease, the characteristics of the claimed medical products and the institutional strategies. To analyze the effect of the interventions on the total cost of the medicines in the lawsuits, bivariate and multivariate linear regressions with variance were performed. For the categorical outcomes, Poisson regressions were performed with robust variance, using a significance level of 5%. RESULTS: A reduction in the costs of medicines in the lawsuits and of the requests for medicines within the SUS formulary was verified after the deployment of the Department of Assessment of Nonstandardized Medicines (DAMNP) and the Technical Chamber of Health Assessment (CATS); an increase in processed prescriptions from the Brazilian Universal Health System was observed after the deployment of the CATS; and an increase in medicines outside the SUS formulary without a therapeutic alternative was verified after the CATS. CONCLUSION: The institutional strategies deployed were important tools to reduce the high costs of the medicines in the lawsuits. In addition, they represented a step forward for the State, provided a benefit to society and indicated a potential path for the health and justice systems of other countries that also face problems caused by the judicialization of health.

l-Buthionine Sulfoximine Detection and Quantification in Polyurea Dendrimer Nanoformulations.

l-Buthionine sulfoximine (l-BSO) is an adjuvant drug that is reported to increase the sensitivity of cancer cells to neoplastic agents. Dendrimers are exceptional drug delivery systems and l-BSO nanoformulations are envisaged as potential chemotherapeutics. The absorption of l-BSO at a low wavelength limits its detection by conventional analytical tools. A simple and sensitive method for l-BSO detection and quantification is now reported. In this study, l-BSO was encapsulated in a folate-targeted generation four polyurea dendrimer (PUREG4-FA2) and its release profile was followed for 24 h at pH 7.4 and 37 °C. The protocol uses in situ l-BSO derivatization, by the formation of a catechol-derived orto-quinone, followed by visible detection of the derivative at 503 nm. The structure of the studied l-BSO derivative was assessed by NMR spectroscopy.

A new methodology for royalties distribution of the Itaipu hydroelectric plant: The hydrographic basin as the unit of analysis.

Over the past few years, many sectors such as energy generation, industry, domestic supply, and agriculture have encountered serious environmental problems due to the lack of rainfall. Thus, the purpose of this paper is to review the current methodology of royalties distribution from Itaipu hydroelectric plant. In the proposed approach, two criteria were considered to establish the division of Itaipu royalties: (1) the relative percentage of the water flow in the generation of electricity and, (2) the relative percentage of the drop in the height of water. 62 hydroelectric plants were evaluated in this study. In 52 plants the water flow was the factor that most contributed to the generation of electricity. In 2013, 346 municipalities benefited the Itaipu royalties. With the proposed methodology, 1,327 municipalities will receive the resource, what would increase the revenue of each of these municipalities by, on average, US$ 87,436.91 per year. The methodology presented herein proposes a reduction in the environmental disparity that now exists in Brazil, through improvement to Government instruments and environmental policies. The distribution of royalties throughout the watershed can provide additional resources to support payment programs for environmental services at the state and municipality levels.

Itaipu royalties: The role of the hydroelectric sector in water resource management.

For countries dependent on hydroelectricity, water scarcity poses a real risk. Hydroelectric plants are among the most vulnerable enterprises to climate change. Investing in the conservation of the hydrographic basin is a solution found by the hydropower sector. Given the importance of the Itaipu plant to the energy matrix of Brazil and Paraguay, the aim of this study is to review the current distribution of royalties from Itaipu, using the hydrographic basin as a of criterion of analysis. Approximately 98.73% of the Itaipu basin is in Brazil. The flow contributes 99% of the total electricity generated there, while the drop height of the water contributes only 1%. Under the current policy, royalties are shared equally between Brazil and Paraguay. In the proposed approach, each country would receive a percentage for their participation in the drop height and water flow in the output of the turbines, which are intrinsic factors for electricity generation. Thus, Brazil would receive 98.35% of the royalties and Paraguay, 1.65%. The inclusion of the hydrographic basin as a criterion for the distribution of royalties will promote more efficient water resource management, since the payment will be distributed throughout the basin of the plant. The methodology can be applied to hydroelectric projects worldwide.

Fuzzy logic applied to prospecting for areas for installation of wood panel industries.

Prospecting for suitable areas for forestry operations, where the objective is a reduction in production and transportation costs, as well as the maximization of profits and available resources, constitutes an optimization problem. However, fuzzy logic is an alternative method for solving this problem. In the context of prospecting for suitable areas for the installation of wood panel industries, we propose applying fuzzy logic analysis for simulating the planting of different species and eucalyptus hybrids in Espírito Santo State, Brazil. The necessary methodological steps for this study are as follows: a) agriclimatological zoning of different species and eucalyptus hybrids; b) the selection of the vector variables; c) the application of the Euclidean distance to the vector variables; d) the application of fuzzy logic to matrix variables of the Euclidean distance; and e) the application of overlap fuzzy logic to locate areas for installation of wood panel industries. Among all the species and hybrids, Corymbia citriodora showed the highest percentage values for the combined very good and good classes, with 8.60%, followed by Eucalyptus grandis with 8.52%, Eucalyptus urophylla with 8.35% and Urograndis with 8.34%. The fuzzy logic analysis afforded flexibility in prospecting for suitable areas for the installation of wood panel industries in the Espírito Santo State can bring great economic and social benefits to the local population with the generation of jobs, income, tax revenues and GDP increase for the State and municipalities involved. The proposed methodology can be adapted to other areas and agricultural crops.

Geotechnology and landscape ecology applied to the selection of potential forest fragments for seed harvesting.

The Atlantic Forest biome is recognized for its biodiversity and is one of the most threatened biomes on the planet, with forest fragmentation increasing due to uncontrolled land use, land occupation, and population growth. The most serious aspect of the forest fragmentation process is the edge effect and the loss of biodiversity. In this context, the aim of this study was to evaluate the dynamics of forest fragmentation and select potential forest fragments with a higher degree of conservation for seed harvesting in the Itapemirim river basin, Espírito Santo State, Brazil. Image classification techniques, forest landscape ecology, and multi-criteria analysis were used to evaluate the evolution of forest fragmentation to develop the landscape metric indexes, and to select potential forest fragments for seed harvesting for the years 1985 and 2013. According to the results, there was a reduction of 2.55% of the occupancy of the fragments in the basin between the years 1985 and 2013. For the years 1985 and 2013, forest fragment units 2 and 3 were spatialized with a high potential for seed harvesting, representing 6.99% and 16.01% of the total fragments, respectively. The methodology used in this study has the potential to be used to support decisions for the selection of potential fragments for seed harvesting because selecting fragments in different environments by their spatial attributes provides a greater degree of conservation, contributing to the protection and conscious management of the forests. The proposed methodology can be adapted to other areas and different biomes of the world.

Tuberculosis patients co-infected with Mycobacterium bovis and Mycobacterium tuberculosis in an urban area of Brazil.

In this cross-sectional study, mycobacteria specimens from 189 tuberculosis (TB) patients living in an urban area in Brazil were characterised from 2008-2010 using phenotypic and molecular speciation methods (pncA gene and oxyR pseudogene analysis). Of these samples, 174 isolates simultaneously grew on Löwenstein-Jensen (LJ) and Stonebrink (SB)-containing media and presented phenotypic and molecular profiles of Mycobacterium tuberculosis, whereas 12 had molecular profiles of M. tuberculosis based on the DNA analysis of formalin-fixed paraffin wax-embedded tissue samples (paraffin blocks). One patient produced two sputum isolates, the first of which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, and the second of which only grew on SB media and presented phenotypic profiles of Mycobacterium bovis. One patient provided a bronchial lavage isolate, which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, but had molecular profiles of M. bovis from paraffin block DNA analysis, and one sample had molecular profiles of M. tuberculosis and M. bovis identified from two distinct paraffin blocks. Moreover, we found a low prevalence (1.6%) of M. bovis among these isolates, which suggests that local health service procedures likely underestimate its real frequency and that it deserves more attention from public health officials.

Overlaid Transcriptional and Proteome Analyses Identify Mitotic Kinesins as Important Targets of Arylsulfonamide-Mediated RBM39 Degradation.

Certain arylsulfonamides (ArSulf) induce an interaction between the E3 ligase substrate adaptor DCAF15 and the critical splicing factor RBM39, ultimately causing its degradation. However, degradation of a splicing factor introduces complex pleiotropic effects that are difficult to untangle, since, aside from direct protein degradation, downstream transcriptional effects also influence the proteome. By overlaying transcriptional data and proteome datasets, we distinguish transcriptional from direct degradation effects, pinpointing those proteins most impacted by splicing changes. Using our workflow, we identify and validate the upregulation of the arginine-and-serine rich protein (RSRP1) and the downregulation of the key kinesin motor proteins KIF20A and KIF20B due to altered splicing in the absence of RBM39. We further show that kinesin downregulation is connected to the multinucleation phenotype observed upon RBM39 depletion by ArSulfs. Our approach should be helpful in the assessment of potential cancer drug candidates which target splicing factors. IMPLICATIONS: Our approach provides a workflow for identifying and studying the most strongly modulated proteins when splicing is altered. The work also uncovers a splicing-based approach toward pharmacologic targeting of mitotic kinesins.

Overlaid transcriptome and proteome analyses identify mitotic kinesins as important targets of arylsulfonamide-mediated RBM39 degradation.

Certain arylsulfonamides (ArSulfs) induce an interaction between the E3 ligase substrate adaptor DCAF15 and the critical splicing factor RBM39, ultimately causing its degradation. However, degradation of a splicing factor introduces complex pleiotropic effects that are difficult to untangle, since, aside from direct protein degradation, downstream transcriptional effects also influence the proteome. By overlaying transcriptional data and proteome datasets, we distinguish transcriptional from direct degradation effects, pinpointing those proteins most impacted by splicing changes. Using our workflow, we identify and validate the upregulation of the argininie-and-serine rich protein (RSRP1) and the downregulation of the key kinesin motor proteins KIF20A and KIF20B due to altered splicing in the absence of RBM39. We further show that kinesin downregulation is connected to the multinucleation phenotype observed upon RBM39 depletion by ArSulfs. Our approach should be helpful in the assessment of potential cancer drug candidates which target splicing factors. Implications: Our approach provides a workflow for identifying and studying the most strongly modulated proteins when splicing is altered; the work also uncovers a splicing-based approach toward pharmacological targeting of mitotic kinesins.

Spoligotyping and variable number tandem repeat analysis of Mycobacterium bovis isolates from cattle in Brazil.

We performed spoligotyping and 12-mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTRs) typing to characterise Mycobacterium bovis isolates collected from tissue samples of bovines with lesions suggestive for tuberculosis during slaughter inspection procedures in abattoirs in Brazil. High-quality genotypes were obtained with both procedures for 61 isolates that were obtained from 185 bovine tissue samples and all of these isolates were identified as M. bovis by conventional identification procedures. On the basis of the spoligotyping, 53 isolates were grouped into nine clusters and the remaining eight isolates were unique types, resulting in 17 spoligotypes. The majority of the Brazilian M. bovis isolates displayed spoligotype patterns that have been previously observed in strains isolated from cattle in other countries. MIRU-VNTR typing produced 16 distinct genotypes, with 53 isolates forming eight of the groups, and individual isolates with unique VNTR profiles forming the remaining eight groups. The allelic diversity of each VNTR locus was calculated and only two of the 12-MIRU-VNTR loci presented scores with either a moderate (0.4, MIRU16) or high (0.6, MIRU26) discriminatory index (h). Both typing methods produced similar discriminatory indexes (spoligotyping h = 0.85; MIRU-VNTR h = 0.86) and the combination of the two methods increased the h value to 0.94, resulting in 29 distinct patterns. These results confirm that spoligotyping and VNTR analysis are valuable tools for studying the molecular epidemiology of M. bovis infections in Brazil.

Age-dependent profile of left-sided infective endocarditis: a 3-center experience.

BACKGROUND: The influence of age on the main epidemiological, clinical, echocardiographic, microbiological, and prognostic features of patients with infective endocarditis remains unknown. We present the series with the largest numbers and range of ages of subjects to date that analyzes the influence of age on the main characteristics of patients with isolated left-sided infective endocarditis. Furthermore, this series is the first one in which patients have been distributed according to age quartile. METHODS AND RESULTS: A total of 600 episodes of left-sided endocarditis consecutively diagnosed in 3 tertiary centers were stratified into age-specific quartiles and 107 variables compared between the different groups. With increasing age, the percentage of women, previous heart disease, predisposing disease (diabetes mellitus and cancer), and infection by enterococci and Streptococcus bovis also increased. Valvular insufficiency and perforation and Staphylococcus aureus infection were more common in younger patients. The therapeutic approach differed depending on patient age because of the growing proportion of older patients who only received medical treatment. Clinical course and hospital prognosis were worse in the older patients because of increased surgical mortality among them. CONCLUSIONS: Increasing age is associated with less valvular impairment (insufficiency and perforation), a more favorable microbiological profile, and increased surgical mortality among adults with left-sided infective endocarditis.

Impact of Height Estimation on Tidal Volume Calculation for Protective Ventilation-A Prospective Observational Study.

OBJECTIVES: The current standard of care to deliver invasive mechanical ventilation support is the protective ventilation approach. One pillar of this approach is the limitation of tidal volume to less than 6 mL/Kg of predicted body weight. Predicted body weight is calculated from patient's height. Yet, little is known about the potential impact of errors arising from visual height estimation, a common practice, to calculate tidal volumes. The aim of this study was to evaluate that impact on tidal volume calculation to use during protective ventilation. DESIGN: Prospective observational study. SETTING: An eight-bed polyvalent ICU. PATIENTS: Adult patients (≥ 18 yr). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tidal volumes were calculated from visual height estimates made by physicians, nurses, and patients themselves and compared with tidal volumes calculated from measured heights. Comparisons were made using the paired t test. Modified Bland-Altman plots were used to assess agreement between height estimates and measurements. One-hundred patients were recruited. Regardless of the height estimator, all the mean tidal volumes would be greater than 6 mL/Kg predicted body weight (all p < 0.001). Additionally, tidal volumes would be greater than or equal to 6.5 mL/Kg predicted body weight in 18% of patients' estimates, 25% of physicians' estimates, and 30% of nurses' estimates. Patients with lower stature (< 165 cm), older age, and surgical typology of admission were at increased risk of being ventilated with tidal volumes above protective threshold. CONCLUSIONS: The clinical benefit of the protective ventilation strategy can be offset by using visual height estimates to calculate tidal volumes. Additionally, this approach can be harmful and potentially increase mortality by exposing patients to tidal volumes greater than or equal to 6.5 mL/Kg predicted body weight. In the interest of patient safety, every ICU patient should have his or her height accurately measured.

Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction--angiographic and intravascular ultrasound--results from the TErapia Celular Aplicada al Miocardio Pilot study.

BACKGROUND: We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). METHODS: Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. RESULTS: No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. CONCLUSIONS: In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy.

Tibialis Posterior Tendon Dislocation: A Case Report.

CASE: A 37-year-old man presented after a sudden snap followed by pain in the medial side of the ankle while playing football. Physical examination showed edema and pain posteriorly to the medial malleolus, and a longitudinal structure was palpable anteriorly. Ultrasound confirmed a dislocated tibialis posterior tendon (TPT). The patient underwent surgery, and the flexor retinaculum was repaired. Six months after the surgery, he was asymptomatic and had resumed his usual physical activity, with an AOFAS score of 100. CONCLUSION: TPT dislocation is rare and orthopaedic surgeons should be aware of this condition in patients with a sudden traumatic medial ankle pain.

Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance.

: Ovarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional therapy based on platinum salts. In this study, we tested the effects of the in vitro inhibition of GSH synthesis on the restoration of ovarian cancer cells sensitivity to carboplatin. GSH synthesis was inhibited by exposing cells to l-buthionine sulfoximine (l-BSO), an inhibitor of -glutamylcysteine ligase (GCL). Given the systemic toxicity of l-BSO, we developed a new formulation using polyurea (PURE) dendrimers nanoparticles (l-BSO@PUREG4-FA2), targeting l-BSO delivery in a folate functionalized nanoparticle.

High discrimination of Mycobacterium bovis isolates in Brazilian herds by spoligotyping.

Bovine tuberculosis is an infectious disease caused by Mycobacterium bovis (M. bovis), that leads to economic losses in infected herds and it is also considered an important zoonosis. The molecular typing methods of M. bovis isolates are fundamental for the bovine tuberculosis surveillance system, and spoligotyping is the standard genotyping technique for this species. Thus, the aim of the present study is to analyze the spatial and cluster distribution of M. bovis strains from several regions of Brazil through molecular typing. Spoligotyping technique was applied on 422 isolates identified as M. bovis, and Ripley's K function was used to perform the spatial and cluster analysis of each identified profile. Forty-three (43) different profiles were identified and spoligotype SB0121 was the most frequent and showed a uniform pattern in the spatial distribution while spoligotypes SB0295, SB1380 and SB1050 formed clusters. In addition, three novel spoligotype profiles (SB2361, SB2362, SB2364) were identified in different herds. In this perspective, it is believed that molecular identification and typing can significantly improve the performance of surveillance systems for bovine tuberculosis in Brazil.