Is the learning curve of the urology resident for conventional radical prostatectomy similar to that of staff initiating robot-assisted radical prostatectomy?

ABSTRACT Introduction: The superiority of the functional results of robot-assisted radical prostatectomyis still controversial. Despite this, it is known that minimally invasive surgery obtains better results when analyzing blood loss, blood transfusion and length of stay, for example. Several studies have analyzed the impact of the resident physician's involvement on the results of urological surgeries. The simple learning curve for robot-assisted radical prostate surgery is estimated to be around 10 to 12 cases. Learning curve data for robotic surgeons is heterogeneous, making it difficult to analyze. Rare studies compare the results of a radical prostatectomy of an inexperienced surgeon starting his training in open surgery, with the results of the same surgeon, a few years later, starting training in robotic surgery. Objective: to analyze the results of open radical prostatectomy surgeries (ORP) performed by urology residents, comparing them to the results of robot-assisted radical prostatectomy (RARP), performed by these same surgeons, after completing their training in urology. Materials and methods: a retrospective analysis of the cases of only 3 surgeons was performed. 50 patients underwent ORP (group A). The surgeons who operated on the ORP patients were in the 3rd and final year of the urology residency program and beginners in ORP surgery, but with at least 4 years of experience in open surgery. The same surgeons, already trained urologists, began their training in robotic surgery and performed 56 RARP surgeries (group B). For the comparative analysis, data were collected on age, number of lymph nodes removed, surgery time, hospitalization time, drain volume, drain permanence time, indwelling bladdercateter (IBC) permanence time, positive surgical margin, biochemical recurrence, risk classification (ISUP), intra and postoperative complications, urinary incontinence (UI) and erectile dysfunction (ED). The console used was the Da Vinci Si, from Intuitive®. For statistical analysis, the Shapiro-Wilk test verified that the data did not follow normality, the Levene test guaranteed homogeneity, and the Mann-Whitney test performed the comparative analysis of the quantitative data. For the analysis of qualitative data, the Chi-square test was used for nominal variables and the Mann-Whitney U test for ordinal variables. Additionally, the Friedman test analyzed whether there was an improvement in the perception of UI or ED over the months, for each group individually (without comparing them), and the post-hoc Durbin-Conover test, for the results with statistically significant difference. We used a p-value < 0.05, and the Jamovi® program (Version 2.0). Results: there was no statistically significant difference between the groups for age, number of lymph nodes removed, positive surgical margin, biochemical recurrence, risk classification and urinary incontinence. Additionally, we observed that the surgical time was longer in group B. On the other hand, the length of stay, drain volume, drain time, IBC time, complication rate and levels of erectile dysfunction in the third and sixth months were higher in group A, when compared to group B. We also observed that there was no evolutionary improvement in ED over the months in both groups, and that there was a perception of improvement in UI from the 1st to the 3rd month in group A, and from the 1st to the 6th month, and from the 3rd to the 12th month, in group B. Conclusion: the learning curve of RARP is equivalent to the curve of ORP. In general, the results for the robotic group were better, however, the functional results were similar between the groups, with a slight tendency of advantage for the robotic arm.

Is the learning curve of the urology resident for conventional radical prostatectomy similar to that of staff initiating robot-assisted radical prostatectomy?

INTRODUCTION: The superiority of the functional results of robot-assisted radical prostatectomyis still controversial. Despite this, it is known that minimally invasive surgery obtains better results when analyzing blood loss, blood transfusion and length of stay, for example. Several studies have analyzed the impact of the resident physician's involvement on the results of urological surgeries. The simple learning curve for robot-assisted radical prostate surgery is estimated to be around 10 to 12 cases. Learning curve data for robotic surgeons is heterogeneous, making it difficult to analyze. Rare studies compare the results of a radical prostatectomy of an inexperienced surgeon starting his training in open surgery, with the results of the same surgeon, a few years later, starting training in robotic surgery. OBJECTIVE: to analyze the results of open radical prostatectomy surgeries (ORP) performed by urology residents, comparing them to the results of robot-assisted radical prostatectomy (RARP), performed by these same surgeons, after completing their training in urology. MATERIALS AND METHODS: a retrospective analysis of the cases of only 3 surgeons was performed. 50 patients underwent ORP (group A). The surgeons who operated on the ORP patients were in the 3rd and final year of the urology residency program and beginners in ORP surgery, but with at least 4 years of experience in open surgery. The same surgeons, already trained urologists, began their training in robotic surgery and performed 56 RARP surgeries (group B). For the comparative analysis, data were collected on age, number of lymph nodes removed, surgery time, hospitalization time, drain volume, drain permanence time, indwelling bladdercateter (IBC) permanence time, positive surgical margin, biochemical recurrence, risk classification (ISUP), intra and postoperative complications, urinary incontinence (UI) and erectile dysfunction (ED). The console used was the Da Vinci Si, from Intuitive®. For statistical analysis, the Shapiro-Wilk test verified that the data did not follow normality, the Levene test guaranteed homogeneity, and the Mann-Whitney test performed the comparative analysis of the quantitative data. For the analysis of qualitative data, the Chi-square test was used for nominal variables and the Mann-Whitney U test for ordinal variables. Additionally, the Friedman test analyzed whether there was an improvement in the perception of UI or ED over the months, for each group individually (without comparing them), and the post-hoc Durbin-Conover test, for the results with statistically significant difference. We used a p-value < 0.05, and the Jamovi® program (Version 2.0). RESULTS: there was no statistically significant difference between the groups for age, number of lymph nodes removed, positive surgical margin, biochemical recurrence, risk classification and urinary incontinence. Additionally, we observed that the surgical time was longer in group B. On the other hand, the length of stay, drain volume, drain time, IBC time, complication rate and levels of erectile dysfunction in the third and sixth months were higher in group A, when compared to group B. We also observed that there was no evolutionary improvement in ED over the months in both groups, and that there was a perception of improvement in UI from the 1st to the 3rd month in group A, and from the 1st to the 6th month, and from the 3rd to the 12th month, in group B. CONCLUSION: the learning curve of RARP is equivalent to the curve of ORP. In general, the results for the robotic group were better, however, the functional results were similar between the groups, with a slight tendency of advantage for the robotic arm.

Spatial analysis of care for patients undergoing dialysis therapy in the state of Minas Gerais, Brazil, between 2015 and 2019.

OBJECTIVE: To analyze the spatial flow of care for patients undergoing dialysis therapy in the health regions of the State of Minas Gerais. METHODS: Ecological study whose population was patients undergoing dialysis therapy in public, philanthropic institutions or whose treatment was paid for by the Unified Health System in private clinics in partnership, in the State of Minas Gerais. Patients were grouped by health region of residence. The proportions of patients who underwent dialysis were calculated, as well as enrollment on the kidney transplant list in their own region of residence or outside it. Person correlations of these proportions with socioeconomic and care indicators of the health regions were estimated. Spatial exploratory techniques estimated general (Moran's I) and local (LISA) spatial correlation coefficients. RESULTS: Regions with higher GDP had a higher number of nephrologists and a higher proportion of registrations in the region of residence. A cluster of regions with low GDP was identified further to the northeast of the State (also with lower nephrologist ratio values), a cluster with a high proportion of those registered on the transplant list in the center of the State, and a cluster with a low proportion of dialysis in the same region of residence further southeast. CONCLUSION: Regional disparities were evident in relation to the proportion of patients registered on the waiting list for kidney transplantation, the proportion of patients undergoing dialysis in the same region of residence and the proportion of patients registered on the waiting list for kidney transplantation in the same region of residence. residence.

Spatial analysis of care for patients undergoing dialysis therapy in the state of Minas Gerais, Brazil, between 2015 and 2019 / Análise espacial da assistência a pacientes em terapia dialítica no Estado de Minas Gerais, Brasil, entre 2015 e 2019

ABSTRACT Objective: To analyze the spatial flow of care for patients undergoing dialysis therapy in the health regions of the State of Minas Gerais. Methods: Ecological study whose population was patients undergoing dialysis therapy in public, philanthropic institutions or whose treatment was paid for by the Unified Health System in private clinics in partnership, in the State of Minas Gerais. Patients were grouped by health region of residence. The proportions of patients who underwent dialysis were calculated, as well as enrollment on the kidney transplant list in their own region of residence or outside it. Person correlations of these proportions with socioeconomic and care indicators of the health regions were estimated. Spatial exploratory techniques estimated general (Moran's I) and local (LISA) spatial correlation coefficients. Results: Regions with higher GDP had a higher number of nephrologists and a higher proportion of registrations in the region of residence. A cluster of regions with low GDP was identified further to the northeast of the State (also with lower nephrologist ratio values), a cluster with a high proportion of those registered on the transplant list in the center of the State, and a cluster with a low proportion of dialysis in the same region of residence further southeast. Conclusion: Regional disparities were evident in relation to the proportion of patients registered on the waiting list for kidney transplantation, the proportion of patients undergoing dialysis in the same region of residence and the proportion of patients registered on the waiting list for kidney transplantation in the same region of residence. residence.

RESUMO Objetivo: Analisar o fluxo espacial da assistência de pacientes em terapia dialítica nas regionais de saúde do estado de Minas Gerais. Métodos: Estudo ecológico que teve como população pacientes incidentes em terapia dialítica em instituições públicas, filantrópicas ou que tiveram seu tratamento custeado pelo Sistema Único de Saúde em clínicas privadas conveniadas, no estado de Minas Gerais. Os pacientes foram agregados por regional de saúde de residência. Foram calculadas as proporções de pacientes que fizeram diálise, bem como a inscrição na lista de transplante renal em sua própria região de residência ou fora dela. Estimadas as correlações de Person destas proporções com indicadores socioeconômicos e assistenciais das regionais de saúde. Técnicas exploratórias espaciais estimaram coeficientes de correlação espacial geral (I de Moran) e local (LISA). Resultados: Regiões com maior PIB apresentaram maior razão de nefrologistas e maior proporção de inscrições na própria região de residência. Identificou-se um cluster de regiões com PIB baixo mais ao nordeste do estado (também com valores mais baixos de razão de nefrologistas), um cluster de alta proporção de inscritos na lista de transplante no centro do estado, e um cluster de baixa proporção de diálise na mesma região de residência mais ao sudeste. Conclusão: Evidenciou-se disparidades regionais em relação à proporção de inscritos na lista de espera para o transplante renal, proporção de pacientes que realizavam diálise na mesma região de residência e proporção de pacientes inscritos na lista de espera para o transplante renal na mesma região de residência.

Antibacterial and antibiofilm activity of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H pyrazoles and thiazoles in multidrug-resistant pathogens.

To find novel antibiotic drugs, six 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H derivatives named 1b, 1d (pyrazoles), 2a, 2b, 2c, and 2d (thiazoles) were evaluated in silico and in vitro. The in silico analyses were based on ADME pharmacokinetic parameters (absorption, distribution, metabolism, and excretion). The in vitro antibacterial activity was evaluated in Gram-positive and Gram-negative species (Staphylococcus aureus ATCC® 25904, Staphylococcus epidermidis ATCC® 35984, Klebsiella pneumoniae ATCC® 700603, and Acinetobacter baumannii ATCC® 19606), by determination of minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), kinetics curve, and antibiofilm assays. As results, the azoles have activity against the Gram-negative species K. pneumoniae ATCC® 700603 and A. baumannii ATCC® 19606. No antibacterial activity was observed for the Gram-positive bacteria evaluated. Thus, the azoles were evaluated against clinical isolates of K. pneumoniae carbapenemase (KPC) and A. baumannii multidrug-resistant (Ab-MDR). All azoles have antibacterial activity against Ab-MDR isolates (Gram-negative) with MIC values between 512 µg/mL and 1,024 µg/mL. Against KPC isolates the azoles 1b, 1d, and 2d present antibacterial activity (MIC = 1,024 µg/mL). In the kinetics curve assay, the 1b and 1d pyrazoles reduced significantly viable cells of Ab-MDR isolates and additionally inhibited 86.6 to 95.8% of the biofilm formation. The in silico results indicate high possibility to permeate the blood-brain barrier (2b) and was predict human gastrointestinal absorption (all evaluated azoles). Considering that the research and development of new antibiotics is a priority for drug-resistant pathogens, our study revealed the antibacterial and antibiofilm activity of novel azoles against K. pneumoniae and A. baumannii pathogens.

Comprehensive adsorption and spectroscopic studies on the interaction of magnetic biochar from black wattle sawdust with beta-blocker metoprolol.

The rise of contaminants of emerging concern in water-resources due to human activities has driven research toward wastewater treatment, specifically adsorption. The utilization of woody biomass for biochar production in adsorption has shown promise due to its high availability. This study shows the preparation of magnetic biochars (MB) from waste black wattle sawdust, utilizing ZnCl2 and NiCl2 (proportions: 1:0.5:0.5 = MB-0.5 and 1:1:1 = MB-1) as activating and magnetic agents. Synthesized via microwave-assisted-pyrolysis, MB boasts a high surface area (up to 765 m2.g-1) and functional groups, enhancing metoprolol medicine adsorption. Nonlinear kinetic and isothermal models were tested; the Avrami fractional-order kinetic model and Liu's isothermal model provided the best fits for experimental data. Thermodynamics and spectroscopic studies revealed spontaneous and exothermic adsorption processes, with physisorption magnitude and dominance of hydrogen-bond and π-π-interactions. MB can be easily extracted from an aqueous medium using magnetic fields, while adsorption capacity could be regenerated through green solvent elution.

Identifying inhibitors of Trypanosoma cruzi nucleoside diphosphate kinase 1 as potential repurposed drugs for Chagas' disease.

Trypanosoma cruzi is the causative agent of Chagas' disease, an endemic and neglected disease. The treatment is limited to only two drugs, benznidazole (BZL) and nifurtimox (NFX), introduced more than fifty years ago and no new advances have been made since then. Nucleoside diphosphate kinases (NDPK) are key metabolic enzymes which have gained interest as drug targets of pathogen organisms. Taking advantage of the computer-assisted drug repurposing approaches, in the present work we initiate a search of potential T. cruzi nucleoside diphosphate kinase 1 (TcNDPK1) inhibitors over an âˆ¼ 12,000 compound structures database to find drugs targeted to this enzyme with trypanocidal activity. Four medicines were selected and evaluated in vitro, ketorolac (KET, an anti-inflamatory), dutasteride (DUT, used to treat benign prostatic hyperplasia), nebivolol and telmisartan (NEB and TEL, used to treat high blood pressure). The four compounds were weak inhibitors and presented different trypanocidal effect on epimastigotes, trypomastigotes and intracellular stages. NEB and TEL were the most active drugs with increased effect on intracellular stages, (IC50 = 2.25 µM and 13.21 µM respectively), and selectivity indexes of 13.01 and 8.59 respectively, showing comparable effect to BZL, the first line drug for Chagas' disease treatment. In addition, both presented positive interactions when combined with BZL. Finally, transgenic epimastigotes with increased expression of TcNDPK1 were more resistant to TEL and NEB, suggesting that TcNDPK1 is at least one of the molecular targets. In view of the results, NEB and TEL could be repurposed medicines for Chagas' disease therapy.

The action of clove (Syzygium aromaticum ) and thyme ( Thymus vulgaris) essential oils in the control of Acanthhoscelides obtectus (Coleoptera: Chrysomelidae) in laboratory.

The objective of this study was to assess the efficiency of essential oils of cloves (Syzygium aromaticum) and thyme (Thymus vulgaris) on the control of Acanthoscelides obtectus in laboratory conditions. The extraction of the oils was executed by the hydro-distillation method in a Clevenger device, for 4 hours and the design used was completely randomized, with five replications, in a 10x8 factorial arrangement (dozes and exposition time) with ten concentrations (20; 10; 5; 2.5; 1.75; 0.75; 0.5; 0.25 and 0.0% and Tween® 5.0%). Each replication was comprised by 10 unsexed insects of A. obtectus. The variables evaluated are as follows: control efficiency and CL50 through the Proc Probit analysis. The evaluations were carried out in 1, 2, 3, 12, 24, 48, 72, and 96 hours after the treatment. The results demonstrate that the essential oils of cloves and thyme caused 100% of mortality after 48 and 72 hours, respectively, in the 20% concentration. The Cl50 was estimated at 30.46 µL mL-1 for the oil of cloves and 24.93 µL mL-1 for the oil of thyme. The use of essential oils of cloves and thyme represent a viable alternative for use in storehouses for the integrated management of A. obtectus.

Bioprospection of the trichomonacidal activity of lipid extracts derived from marine macroalgae Gigartina skottsbergii.

Algal extracts are sources of bioactive substances with applications in the development of novel alternative drugs against several diseases, including trichomoniasis sexually transmitted infection caused by Trichomonas vaginalis. Factors such as clinical failures and resistant strains limit the success of the existing drugs available for treating this disease. Therefore, searching for viable alternatives to these drugs is essential for the treatment of this disease. The present study was conducted for, in vitro and in silico characterization of extracts obtained from marine macroalgae Gigartina skottsbergii at stages gametophidic, cystocarpic, and tetrasporophidic. In addition, antiparasitic activity of these extracts against the ATCC 30236 isolate of T. vaginalis, their cytotoxicity, and gene expression of trophozoites after treatment were evaluated. The minimum inhibitory concentration and 50% inhibition concentration were determined for each extract. Results: In vitro analysis of the extracts' anti-T. vaginalis activity revealed an inhibitory effect of 100%, 89.61%, and 86.95% for Gigartina skottsbergii at stages gametophidic, cystocarpic, and tetrasporophidic, respectively, at 100 µg/mL. In silico analysis revealed the interactions between constituents of the extracts and enzymes from T. vaginalis, with significant free energy values obtained for the binding. None of the extract concentrations exhibited cytotoxic effects on VERO cell line compared to control, while cytotoxicity on HMVII vaginal epithelial cells line was observed at 100 µg/mL (30% inhibition). Gene expression analysis revealed differences in the expression profile of T. vaginalis enzymes between the extract-treated and control groups. According to these results, Gigartina skottsbergii extracts exhibited satisfactory antiparasitic activity.

Effectiveness of the repurposed drug isotretinoin in an experimental murine model of Chagas disease.

Benznidazole and nifurtimox are the drugs currently used for the treatment of Chagas disease, however its side effects may affect patient adherence. In the search for new alternative therapies, we previously identified isotretinoin (ISO), an FDA-approved drug widely used for the treatment of severe acne through a drug repurposing strategy. ISO shows a strong activity against Trypanosoma cruzi parasites in the nanomolar range, and its mechanism of action is through the inhibition of T. cruzi polyamine and amino acid transporters from the Amino Acid/Auxin Permeases (AAAP) family. In this work, a murine model of chronic Chagas disease (C57BL/6 J mice), intraperitoneally infected with T. cruzi Nicaragua isolate (DTU TcI), were treated with different oral administrations of ISO: daily doses of 5 mg/kg/day for 30 days and weekly doses of 10 mg/kg during 13 weeks. The efficacy of the treatments was evaluated by monitoring blood parasitemia by qPCR, anti-T. cruzi antibodies by ELISA, and cardiac abnormalities by electrocardiography. No parasites were detected in blood after any of the ISO treatments. The electrocardiographic study of the untreated chronic mice showed a significant decrease in heart rate, while in the treated mice this negative chronotropic effect was not observed. Atrioventricular nodal conduction time in untreated mice was significantly longer than in treated animals. Mice treated even with ISO 10 mg/kg dose every 7 days, showed a significant reduction in anti-T. cruzi IgG levels. In conclusion, the intermittent administration of ISO 10 mg/kg would improve myocardial compromise during the chronic stage.

Carrageenan from Gigartina skottsbergii: A Novel Molecular Probe to Detect SARS-CoV-2.

The COVID-19 pandemic has caused an unprecedented health and economic crisis, highlighting the importance of developing new molecular tools to monitor and detect SARS-CoV-2. Hence, this study proposed to employ the carrageenan extracted from Gigartina skottsbergii algae as a probe for SARS-CoV-2 virus binding capacity and potential use in molecular methods. G. skottsbergii specimens were collected in the Chilean subantarctic ecoregion, and the carrageenan was extracted -using a modified version of Webber's method-, characterized, and quantified. After 24 h of incubation with an inactivated viral suspension, the carrageenan's capacity to bind SARS-CoV-2 was tested. The probe-bound viral RNA was quantified using the reverse transcription and reverse transcription loop-mediated isothermal amplification (RT-LAMP) methods. Our findings showed that carrageenan extraction from seaweed has a similar spectrum to commercial carrageenan, achieving an excellent proportion of binding to SARS-CoV-2, with a yield of 8.3%. Viral RNA was also detected in the RT-LAMP assay. This study shows, for the first time, the binding capacity of carrageenan extracted from G. skottsbergii, which proved to be a low-cost and highly efficient method of binding to SARS-CoV-2 viral particles.

Reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay as a rapid molecular diagnostic tool for COVID-19 in healthcare workers.

In December 2019, the Chinese Center for Disease Control (CDC of China) reported an outbreak of pneumonia in the city of Wuhan (Hubei province, China) that haunted the world, resulting in a global pandemic. This outbreak was caused by a betacoronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several of these cases have been observed in healthcare professionals working in hospitals and providing care on the pandemic's frontline. In the present study, nasopharyngeal swab samples of healthcare workers were used to assess the performance of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay and subsequently compared with the real-time reverse-transcription quantitative PCR (RT-qPCR) method. Thus, in this study, we validated a method for detecting SARS-CoV-2 based on RT-LAMP that can be used to diagnose these workers. The methodology used was based on analyzing the sensitivity, specificity, evaluation of the detection limit, and cross-reaction with other respiratory viruses. The agreement was estimated using a dispersion diagram designed using the Bland-Altman method. A total of 100 clinical specimens of nasopharyngeal swabs were collected from symptomatic and asymptomatic healthcare workers in Pelotas, Brazil, during the SARS-CoV-2 outbreak. RT-LAMP assay, it was possible to detect SARS-CoV-2 in 96.7% of the healthcare professionals tested using the E gene and N gene primers approximately and 100% for the gene of human ß-actin. The observed agreement was considered excellent for the primer set of the E and N genes (k = 0.957 and k = 0.896), respectively. The sensitivity of the RT-LAMP assay was positive for the primer set of the E gene, detected to approximately 2 copies per reaction. For the primer set of the N gene, the assay was possible to verify an LoD of approximately 253 copies per reaction. After executing the RT-LAMP assay, no positive reactions were observed for any of the virus respiratory tested. Therefore, we conclude that RT-LAMP is effective for rapid molecular diagnosis during the COVID-19 outbreak period in healthcare professionals.

Coronal-plane leg alignment in adolescence and the effects of activity: A full leg length MRI study.

The aim of this study was to explore the association between developing coronal-plane leg alignment and activity levels during adolescence. We performed a cross-sectional cohort study with individuals from soccer club academies and an age-matched control population. Outcome measures were the hip knee angle (HKA), medial proximal tibial physeal angle (MPTPhyA), lateral distal femoral physeal angle (LDFPhyA) on full leg length magnetic reasonance imagine scans, and the physical activity questionnaire (PAQ) score. The cohort comprised 57 elite male soccer players, 34 male and 34 female controls aged 11-21 years. Mean HKA became more varus with age, with little change after 16 years or skeletal maturity. Skeletally mature elite male soccer players were significantly more varus than male controls with a HKA 2.28° less than male controls (p < 0.001). Skeletally mature male controls had a HKA 1.34° less than female controls (p < 0.001). A negative correlation existed between HKA and PAQ score (coefficient -0.24, p = 0.029). A positive correlation existed between HKA and MPTPhyA (coefficient 0.32, p = 0.008). In conclusion, high activity levels during adolescence are associated with the development of varus leg alignment. Mean HKA becomes more varus with age until skeletal maturity. The development of varus alignment may represent a physiological adaptation to load at the proximal tibial physis. Clinical Significance: A time period may exist for intervention before the development of varus leg alignment in young athletes, such as training load modification or proximal tibial morphology monitoring.

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones.

The broad application of 1H-indazoles has prompted the development of several approaches for the synthesis of such compounds, including metal-free, palladium-, or copper-promoted intramolecular N-arylation of in situ-generated or isolated o-haloarylhydrazones. Such methods mainly start from o-bromo derivatives due to the better yield observed when compared to those obtained from o-chloroarylhydrazones. However, the o-chloroarylaldehydes and o-chloroarylketones used to prepare the arylhydrazones are more commercially available and less expensive than brominated analogs. Seeking to cover a lack in the literature, this work reports a convenient protocol for the synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of o-chlorinated arylhydrazones. Therefore, a series of seven N-phenyl derivatives and a series of six novel N-thiazolyl derivatives was obtained in 10-70% and 12-35% yield, respectively, after stirring the o-chlorinated arylhydrazones, CuI, KOH, and 1,10-phenantroline for 12-48 hours in DMF at 120 °C. The products were isolated by column chromatography on silica gel. All products were fully characterized by HRMS as well as 1H and 13C NMR spectroscopy. Thus, this approach is valuable for promoting the synthesis of N-phenyl-1H-indazoles in a higher yield than that reported in the literature using copper catalysis and the same substrates. This study also prompted the first reported synthesis of pharmacologically interesting N-thiazolyl derivatives.

Fatores associados à não adesão ao regime terapêutico de pacientes em hemodiálise / Factors associated with non-adherence to the treatment regimen in patients in hemodialysis

Resumo Introdução A doença renal crônica apresenta-se como um problema de saúde pública por causa de sua prevalência, dos custos envolvidos no tratamento e da alta taxa de morbimortalidade. Objetivo Avaliar a não adesão ao regime terapêutico de pacientes em hemodiálise e fatores associados. Método Estudo transversal com pacientes que realizam hemodiálise em um hospital universitário e duas clínicas privadas conveniadas ao Sistema Único de Saúde. Padrões para avaliação da não adesão ao regime terapêutico hemodialítico tiveram como base os indicadores estabelecidos pelo The Dialysis Outcomes and Practice Patterns Study: restrição hídrica, regime dietético, regime medicamentoso e terapia hemodialítica. Não conformidade em pelo menos um dos aspectos do tratamento foi considerada não aderência à terapêutica. Resultados Indivíduos com idade inferior a 60 anos tiveram maior probabilidade de não aderir à restrição hídrica, à terapêutica e aos regimes dietético e medicamentoso. Pacientes anúricos tiveram maior chance de não adesão à restrição hídrica e à terapêutica. Indivíduos com hipoalbuminemia e hipoemoglobinemia tiveram maior probabilidade de não aderir à restrição hídrica, enquanto pacientes que se autodeclararam não brancos apresentaram maior chance de não aderir à terapêutica. Nenhuma variável explicativa da adesão à terapia hemodialítica se manteve significativa no modelo final da regressão logística. Conclusão A inconformidade relacionada aos aspectos do tratamento pode resultar em aumento de hospitalização e gastos com saúde, piora do estado clínico, maiores intercorrências no tratamento e aumento da taxa de mortalidade.

Abstract Background Chronic kidney disease presents itself as a public health problem because of its prevalence, the costs involved in treatment and the high rate of morbidity and mortality. Objective To evaluate non-adherence to the therapeutic regimen of hemodialysis patients and associated factors. Method A cross-sectional study with patients undergoing hemodialysis at a University Hospital and two private clinics agreed to the Unified Health System. Standards for non-adherence to the hemodialysis regimen were based on indicators established by The Dialysis Outcomes and Practice Patterns Study: water restrictions, dietary, drug regimen, and hemodialysis therapy. Non-compliance in at least one aspect of treatment was considered non-adherence to therapy. Results Individuals younger than 60 years were more likely to be non-adherent to water restriction, dietary and drug regimens, and therapy. Anuric patients were more likely to be non-adherent to water restriction and therapy. Individuals with hypoalbuminemia and hypohemoglobinemia were more likely not to adhere to water restriction, while patients who self-declared themselves to be non-whites had a higher chance of not adhering to therapy. No explanatory variables of adherence to hemodialysis therapy remained significant in the final logistic regression model. Conclusion Non-conformity related to treatment aspects can result in increased hospitalization and health expenses, worsening of clinical status, greater intercurrences in treatment and increase in mortality rate.

Synthetic Activity of Recombinant Whole Cell Biocatalysts Containing 2-Deoxy-D-ribose-5-phosphate Aldolase from Pectobacterium atrosepticum.

In nature 2-deoxy-D-ribose-5-phosphate aldolase (DERA) catalyses the reversible formation of 2-deoxyribose 5-phosphate from D-glyceraldehyde 3-phosphate and acetaldehyde. In addition, this enzyme can use acetaldehyde as the sole substrate, resulting in a tandem aldol reaction, yielding 2,4,6-trideoxy-D-erythro-hexapyranose, which spontaneously cyclizes. This reaction is very useful for the synthesis of the side chain of statin-type drugs used to decrease cholesterol levels in blood. One of the main challenges in the use of DERA in industrial processes, where high substrate loads are needed to achieve the desired productivity, is its inactivation by high acetaldehyde concentration. In this work, the utility of different variants of Pectobacterium atrosepticum DERA (PaDERA) as whole cell biocatalysts to synthesize 2-deoxyribose 5-phosphate and 2,4,6-trideoxy-D-erythro-hexapyranose was analysed. Under optimized conditions, E. coli BL21 (PaDERA C-His AA C49M) whole cells yields 99 % of both products. Furthermore, this enzyme is able to tolerate 500 mM acetaldehyde in a whole-cell experiment which makes it suitable for industrial applications.

Improvement of the Quality of Recycled Concrete Aggregate Subjected to Chemical Treatments: A Review.

The main factor that alters the quality of recycled concrete aggregate (RCA) is the paste adhered to the natural aggregate (NA). Since it causes weakening of the interfacial transition zone (ITZ) between the aggregate and the cementitious paste, it becomes a determining factor for the mechanical behavior of concrete. It turns out that it is critical to enhance this interface by improving the surface of the aggregate or by removing the paste adhered to the NA. Considering the variety of methods for removing paste adhered to RCA-namely using acids such as hydrochloric acid (HCl), sulfuric acid (H2SO4), and phosphoric acid (H3PO4), among others-this paper presents a review of treatments for the removal of adhered paste using acidic solutions on the RCA, and their influence on the mechanical properties and durability of concrete produced with RCA. Pearson's correlation was used in the statistical analysis to determine the linear relationship of the main factors-for instance, immersion time, acidic solution, and aggregate size-involved in the removal of the paste in the RCA.

Dihydropyrimidinones Against Multiresistant Bacteria.

The increase in bacterial resistance to antimicrobials has led to high morbidity and mortality rates, posing a major public health problem, requiring the discovery of novel antimicrobial substances. The biological samples were identified as the Gram-negative bacilli Acinetobacter baumannii, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Morganella morgannii, Pseudomonas aeruginosa and Serratia marcescens and the Gram-positive cocci Enterococcus faecium, and Staphylococcus aureus, all of them resistant to at least three classes of antimicrobials. The antibacterial activity of the compounds was checked in vitro by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) by the broth microdilution method and plating in brain heart infusion (BHI) agar, respectively. The chemical characterization of the compounds was performed by measuring the melting point and gas chromatography coupled with mass spectrometry (GC-MS) on a Shimadzu GC-MS-QP system 2010SE. Synthetic compounds showed antimicrobial activity against Gram-positive cocci at MIC concentrations 0.16-80 µg/ml and Gram-negative bacilli at MIC concentrations 23.2-80 µg/ml. Enterococcus faecium and S. aureus had the best MIC values. The results of the cytotoxicity test indicated that the synthetic compounds showed no significant difference in three concentrations tested (5, 20, and 80 µg/ml), allowing cell viability not different from that assigned to the control, without the tested compounds. In this context, the development of DHPM derivatives brings an alternative and perspective on effectiveness of drugs as potential future antimicrobial agents.

Revisiting trypanosomatid nucleoside diphosphate kinases.

BACKGROUND: An increasing amount of research has led to the positioning of nucleoside diphosphate kinases (NDPK/NDK) as key metabolic enzymes among all organisms. They contribute to the maintenance the intracellular di- and tri- phosphate nucleoside homeostasis, but they also are involved in widely diverse processes such as gene regulation, apoptosis, signal transduction and many other regulatory roles. OBJETIVE: Examine in depth the NDPKs of trypanosomatid parasites responsible for devastating human diseases (e.g., Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.) which deserve special attention. METHODS: The earliest and latest advances in the topic were explored, focusing on trypanosomatid NDPK features, multifunctionality and suitability as molecular drug targets. FINDINGS: Trypanosomatid NDPKs appear to play functions different from their host counterparts. Evidences indicate that they would perform key roles in the parasite metabolism such as nucleotide homeostasis, drug resistance, DNA damage responses and gene regulation, as well as host-parasite interactions, infection, virulence and immune evasion, placing them as attractive pharmacological targets. MAIN CONCLUSIONS: NDPKs are very interesting multifunctional enzymes. In the present review, the potential of trypanosomatid NDPKs was highlighted, raising awareness of their value not only with respect to parasite biology but also as molecular targets.

X-ray diffraction and in vivo studies reveal the quinary structure of Trypanosoma cruzi nucleoside diphosphate kinase 1: a novel helical oligomer structure.

Trypanosoma cruzi is a flagellated protozoan parasite that causes Chagas disease, which represents a serious health problem in the Americas. Nucleoside diphosphate kinases (NDPKs) are key enzymes that are implicated in cellular energy management. TcNDPK1 is the canonical isoform in the T. cruzi parasite. TcNDPK1 has a cytosolic, perinuclear and nuclear distribution. It is also found in non-membrane-bound filaments adjacent to the nucleus. In the present work, X-ray diffraction and in vivo studies of TcNDPK1 are described. The structure reveals a novel, multi-hexameric, left-handed helical oligomer structure. The results of directed mutagenesis studies led to the conclusion that the microscopic TcNDPK1 granules observed in vivo in T. cruzi parasites are made up by the association of TcNDPK1 oligomers. In the absence of experimental data, analysis of the interactions in the X-ray structure of the TcNDPK1 oligomer suggests the probable assembly and disassembly steps: dimerization, assembly of the hexamer as a trimer of dimers, hexamer association to generate the left-handed helical oligomer structure and finally oligomer association in a parallel manner to form the microscopic TcNDPK1 filaments that are observed in vivo in T. cruzi parasites. Oligomer disassembly takes place on the binding of substrate in the active site of TcNDPK1, leading to dissociation of the hexamers. This study constitutes the first report of such a protein arrangement, which has never previously been seen for any protein or NDPK. Further studies are needed to determine its physiological role. However, it may suggest a paradigm for protein storage reflecting the complex mechanism of action of TcNDPK1.