Exploring Natural Alkaloids from Brazilian Biodiversity as Potential Inhibitors of the Aedes aegypti Juvenile Hormone Enzyme: A Computational Approach for Vector Mosquito Control.

This study explores the potential inhibitory activity of alkaloids, a class of natural compounds isolated from Brazilian biodiversity, against the mJHBP enzyme of the Aedes aegypti mosquito. This mosquito is a significant vector of diseases such as dengue, zika, and chikungunya. The interactions between the ligands and the enzyme at the molecular level were evaluated using computational techniques such as molecular docking, molecular dynamics (MD), and molecular mechanics with generalized Born surface area (MMGBSA) free energy calculation. The findings suggest that these compounds exhibit a high binding affinity with the enzyme, as confirmed by the binding free energies obtained in the simulation. Furthermore, the specific enzyme residues that contribute the most to the stability of the complex with the compounds were identified: specifically, Tyr33, Trp53, Tyr64, and Tyr129. Notably, Tyr129 residues were previously identified as crucial in the enzyme inhibition process. This observation underscores the significance of the research findings and the potential of the evaluated compounds as natural insecticides against Aedes aegypti mosquitoes. These results could stimulate the development of new vector control agents that are more efficient and environmentally friendly.

The role of the antioxidant system and the photosynthetic behavior of paraquat-resistant Conyza sumatrensis in Brazil.

Greenhouse experiments were carried out aiming to characterize-morphologically and biochemically-resistant and susceptible plants of C. sumatrensis. Two experiments were carried out to evaluate the behavior of morphological variables such as leaf area, height, and dry biomass weight, without application of paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride). Other experiments were conducted with two rates of paraquat application (0 and 800 g a.i ha-1); physiological variables were assessed at 2, 4, and 24 h after application (HAA), and plants were collected at 4 HAA for biochemical analyses of antioxidant enzymes and cell membrane peroxidation level. Without herbicide application, paraquat-resistant populations had higher dry biomass, leaf area, liquid photosynthetic rate, carboxylation efficiency, and stomatal conductance. The recovery of the photosynthetic apparatus by resistant plants after paraquat application is rapid (16 HAA) and, in general, presents physiological improvements in terms of photosynthetic rate and carboxylation efficiency. After paraquat treatment, the antioxidant system enzymes of resistant plants showed increased activity and decreased membrane peroxidation, indicating that these enzymes play an important role in the resistance mechanism of these plants.

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study).

PURPOSE: To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2). PATIENTS AND METHODS: Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score. RESULTS: Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1). CONCLUSIONS: The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs.

An In Silico Investigation to Explore Anti-Cancer Potential of Foeniculum vulgare Mill. Phytoconstituents for the Management of Human Breast Cancer.

Breast cancer is one of the most prevalent cancers in the world. Traditionally, medicinal plants have been used to cure various types of diseases and disorders. Based on a literature survey, the current study was undertaken to explore the anticancer potential of Foeniculum vulgare Mill. phytoconstituents against breast cancer target protein (PDB ID: 6CHZ) by the molecular docking technique. Molecular docking was done using Autodock/vina software. Toxicity was predicted by the Protox II server and drug likeness was predicted by Molinspiration. 100 ns MD simulation of the best protein-ligand complexes were done using the Amber 18 tool. The present molecular docking investigation has revealed that among the 40 selected phytoconstituents of F. vulgare, α-pinene and D-limonene showed best binding energy (-6 and -5.9 kcal/mol respectively) with the breast cancer target. α-Pinene and D-limonene followed all the parameters of toxicity, and 100 ns MD simulations of α-pinene and D-limonene complexes with 6CHZ were found to be stable. α-Pinene and D-limonene can be used as new therapeutic agents to cure breast cancer.

A Computational Approach Applied to the Study of Potential Allosteric Inhibitors Protease NS2B/NS3 from Dengue Virus.

Dengue virus (DENV) is a danger to more than 400 million people in the world, and there is no specific treatment. Thus, there is an urgent need to develop an effective method to combat this pathology. NS2B/NS3 protease is an important biological target due it being necessary for viral replication and the fact that it promotes the spread of the infection. Thus, this study aimed to design DENV NS2B/NS3pro allosteric inhibitors from a matrix compound. The search was conducted using the Swiss Similarity tool. The compounds were subjected to molecular docking calculations, molecular dynamics simulations (MD) and free energy calculations. The molecular docking results showed that two compounds, ZINC000001680989 and ZINC000001679427, were promising and performed important hydrogen interactions with the Asn152, Leu149 and Ala164 residues, showing the same interactions obtained in the literature. In the MD, the results indicated that five residues, Lys74, Leu76, Asn152, Leu149 and Ala166, contribute to the stability of the ligand at the allosteric site for all of the simulated systems. Hydrophobic, electrostatic and van der Waals interactions had significant effects on binding affinity. Physicochemical properties, lipophilicity, water solubility, pharmacokinetics, druglikeness and medicinal chemistry were evaluated for four compounds that were more promising, showed negative indices for the potential penetration of the Blood Brain Barrier and expressed high human intestinal absorption, indicating a low risk of central nervous system depression or drowsiness as the the side effects. The compound ZINC000006694490 exhibited an alert with a plausible level of toxicity for the purine base chemical moiety, indicating hepatotoxicity and chromosome damage in vivo in mouse, rat and human organisms. All of the compounds selected in this study showed a synthetic accessibility (SA) score lower than 4, suggesting the ease of new syntheses. The results corroborate with other studies in the literature, and the computational approach used here can contribute to the discovery of new and potent anti-dengue agents.

Biological maturation influences selection process in youth elite soccer players.

This study examined the influence of birth date, salivary testosterone [sT] concentration, sexual maturity status, and general strength on the selection process of an elite Brazilian soccer club during a 12-month period, which was a 2nd phase of a 24-month selection process. The stature, body mass, sT, sexual maturity status [Tanner scale], and hand grip strength were assessed for 143 players during 2 weeks. From these 143 players, 100 players were dismissed [DIS] and 43 players were selected to integrate the club's under-14 squad. Following 1-year training period, the under-14 team was assembled with 9 players designated as starters [STA], and then, comparisons were conducted taking into account a group of non-starters (selected; SEL = 34 players) and STA (n = 09). The DIS, SEL, STA players, and reference population, were compared for birth distribution. A greater proportion of players was born in the first trimester in the STA [75.0%], SEL [57.1%] and DIS [50.0%] groups compared to the reference population [25.8%]. One-way ANOVA showed a higher sT for STA group [516.0 ± 129.9 pmol·L-1], compared to SEL [415.5 ± 117.9 pmol·L-1] and DIS groups [390.9 ± 84.9 pmol·L-1; p = 0.003), and Kruskall-Wallis test showed a higher gonadal development for STA compared to DIS [p = 0.001]. The current findings suggest a strong influence of birth date and biological maturation on young soccer players selection process. Soccer coaches should consider these influences when making decisions about player selection of elite youth players.

Sequencing radium 223 and other life-prolonging agents in castration-resistant prostate cancer patients.

Background: Radium 223 (RA223) is currently administered as part of a therapeutic sequence with the other life-prolonging agents (LPAs) for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: We retrospectively reviewed the clinical records of patients who had received at least three LPAs including RA223. Results: Median overall survival (OS) from the start of first-line treatment was 39.8 months, with the patients who completed all six planned courses of RA223 having a longer OS than those who did not (53.2 vs 29.5 months; p < 0.0001). Conclusions: Our study confirms the activity of RA223 regardless of the treatment line in which it is administered and suggests that patient selection plays a central role in maximizing this activity.

A National Multicenter Study on overall survival in elderly metastatic castrate-resistant prostate cancer patients treated with Radium-223.

BACKGROUND: Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population. AIMS: Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age. METHODS: 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients' parameters. The whole cohort was divided into two groups based on the age of the patients (< 75 years old and ≥ 75 years old). RESULTS: 47% of the patients were < 75 years old and 53% were ≥ 75 years old. The primary outcome, OS, does not show significant differences between the two subgroups if other basal parameters are considered. Considering clinical covariates in univariate models (p < 0.05) several clinical aspects have an impact on OS, except for age (p = 0.072). Age continues to have no significant impact on the OS (p = 0.274) even in multivariate models in the two groups. The toxic effects are similar in the two groups. CONCLUSIONS: Radium-223 prolongs survival in both younger and older patients at the same baseline condition and is a good option in the symptomatic mCRPC setting compared to other agents.

Unibody design for aortic disease with a narrow aortic bifurcation: tips and tricks for success.

BACKGROUND: Surgical management of patients with abdominal aortic diseases associated with distal narrowing is a challenging situation. OBJECTIVES: To evaluate outcomes of unibody bifurcated endovascular stent graft repair. METHODS: This is a retrospective, observational, multi-institutional database study of a cohort of consecutive cases, approved by the local Ethics Committee. Records were reviewed of patients diagnosed from 2010 to 2020 with "shaggy" aorta, saccular aneurysm, penetrating aortic ulcer, and isolated aortic dissection located in the infrarenal abdominal aorta. All patients were treated with a unibody bifurcated stent graft. Main outcomes were technical success, procedure complications, long-term patency, and mortality in the follow-up period up to 5 years. Data on demographics, comorbidities, surgical management, and outcomes were analyzed. RESULTS: Twenty-three patients were treated with unibody bifurcated stent graft repair, including 7 cases of "shaggy" aorta, 3 isolated dissections of the abdominal aorta, 4 penetrating aortic ulcers, and 9 saccular aneurysms. Immediate technical success was achieved in 100% of cases. At follow-up, all stent grafts remained patent and there were no limb occlusions. The patients were symptom-free and reported no complications related to the procedure. There were 5 deaths during the follow-up period (median= 4 years), but none were related to the procedure and there were no aorta-related deaths. CONCLUSIONS: The present study shows that unibody bifurcated stent grafting is safe and effective in this group of patients with narrow distal abdominal aorta and complex aortic pathology. The results were similar for both infrarenal aortic aneurysms and aorto-iliac atherosclerotic disease.

CONTEXTO: O manejo cirúrgico de pacientes com doenças da aorta abdominal associadas ao estreitamento distal é desafiador. OBJETIVOS: Avaliar os desfechos do reparo endovascular com endoprótese bifurcada do tipo monobloco. MÉTODOS: Foi realizado um estudo retrospectivo, de coorte observacional, de banco de dados multi-institucional, com casos consecutivos, após aprovação pelo Comitê de Ética local. Foram analisados prontuários de pacientes com diagnóstico de shaggy aorta, aneurisma sacular, úlcera penetrante da aorta e dissecção isolada da aorta localizados na aorta abdominal infrarrenal entre 2010 e 2020; todos os pacientes foram tratados com endoprótese bifurcada do tipo monobloco. Os principais desfechos foram sucesso técnico, complicações relacionadas ao procedimento, perviedade de longo prazo e mortalidade no seguimento de até 5 anos. Foram incluídos dados demográficos, comorbidades, manejo cirúrgico e desfechos. RESULTADOS: Vinte e três pacientes foram tratados com endoprótese bifurcada do tipo monobloco, incluindo 7 casos de shaggy aorta, 3 dissecções isoladas da aorta abdominal, 4 úlceras penetrantes da aorta e 9 aneurismas saculares. Sucesso técnico imediato foi obtido em 100% dos casos. No seguimento, todas as endopróteses permaneceram pérvias e não houve oclusões de membros. Os pacientes estavam sem sintomas e não relataram complicações relacionadas ao procedimento. Ocorreram 5 óbitos durante o seguimento (mediana = 4 anos), mas nenhum relacionado ao procedimento ou à aorta. CONCLUSÕES: O presente estudo mostra que a endoprótese bifurcada do tipo monobloco é segura e eficaz neste grupo de pacientes com estreitamento distal da aorta abdominal e patologia aórtica complexa. Os resultados foram semelhantes para aneurismas da aorta infrarrenal e doença aterosclerótica aortoilíaca.

The Clinical Efficacy of Radium-223 for Bone Metastasis in Patients with Castration-Resistant Prostate Cancer: An Italian Clinical Experience.

BACKGROUND/AIM: Prostate cancer frequently causes bone metastases and skeletal events that impair quality of life (QoL) and survival. The alpha emitter radium-223 is a new drug that improves treatment in men with castration-resistant prostate cancer (CRPC) and bone metastases. Our aim was to evaluate the effectiveness of radium-223. SUBJECTS AND METHODS: In this retrospective study we enrolled 48 subjects. Pain reduction, alkaline phosphatase (ALP), time to first symptomatic skeletal event, and QoL were the variables we evaluated. RESULTS: Radium-223 was well tolerated, with a manageable toxicity profile and a modest objective response rate. A considerable difference in serum ALP levels before and after treatment was observed, with a significant correlation between pain relief and QoL, which showed a value of R2 to 0.44 with a slope of 1.50 (p = 0.0021). CONCLUSIONS: Radium-223 showed a clinical benefit, with a reduction in pain symptoms in 58% of patients. Radium-223 was shown to be an effective and well-tolerated therapeutic option in patients with metastatic CRPC progressing after docetaxel plus prednisone treatment.

Inferior gluteal artery pseudoaneurysm after fall from a bicycle: case report.

Pseudoaneurysms of gluteal arteries are rare, especially involving the inferior gluteal artery. They are mainly associated with penetrating trauma, infections, or pelvic fractures. A minority of cases are caused by blunt traumas, with only six cases reported in English. We present a case of pseudoaneurysm of the right inferior gluteal artery after a bicycle fall, presenting with a large hematoma in the gluteal region, observed during clinical examination, and significantly reduced hemoglobin. CT angiography revealed a large hematoma, with contrast extravasation and pseudoaneurysm formation. Angiography revealed that the origin of the lesion was in the right inferior gluteal artery. This artery was embolized with coils. After the procedure, the patient was referred to an intensive care unit, from where he was later transferred to a different hospital, with bleeding controlled. Endovascular treatment of these cases is a safe, fast and an effective option.

Lymphoscintigraphy with peritumoral injection versus lymphoscintigraphy with subdermal periareolar injection of technetium-labeled human albumin to identify sentinel lymph nodes in breast cancer patients.

BACKGROUND: Preoperative lymphoscintigraphy is without doubt a valid method for the detection of the sentinel lymph node (SLN). There has been considerable debate regarding the optimal site for the introduction of the tracer; various sites include peritumoral (PT), periareolar (PA), subdermal, and intradermal injection. PURPOSE: To evaluate retrospectively the lymphoscintigraphic identification rate of peritumoral (PT) injection versus subdermal periareolar (PA) injection in the detection of SLNs in breast cancer. MATERIAL AND METHODS: Between October 2002 and December 2011, a cohort of 906 consecutive patients with biopsy proven breast cancer underwent 914 SLN biopsy procedures. A total of 339 procedures (Group A) were performed using a PT deep injection of radiotracer while 575 procedures (Group B) adopted a subdermal PA injection of radiotracer towards the upper outer quadrant, regardless of the site of the carcinoma. All the patients underwent synchronous excision of the breast cancer and SLN biopsy. RESULTS: SLNs were identified in the lymphoscintigram in 308/339 cases (90.85%) of Group A (PT injection) and in 537/575 cases (93.39%) of Group B (PA injection). Furthermore, in 2/339 patients (0.58%) of Group A, internal mammary lymph nodes were found at lymphoscintigraphy, whereas no internal mammary sentinel nodes were found in the Group B patients. The intraoperative identification rate of axillary SLNs was 99.41% (337 of 339) in the Group A patients and 99.65% (573 of 575) in the Group B patients. There was no significant difference in the two groups between the incidence of the number of SLNs detected and the incidence of identification of positive SLNs. CONCLUSION: PT versus PA injection of radiotracer showed comparable success rates for axillary SLN identification, and can be considered a rapid and reliable method.

Glyphosate hormesis induced by treatment via seed stimulates the growth and biomass accumulation in soybean seedlings.

Glyphosate hormesis, identified as a potential means to enhance crop yields, encounters practical constraints because it is typically assessed through foliar applications. The expression and extend of hormesis in this approach are influenced by unpredictable environmental conditions, highlighting the need to explore alternative glyphosate application methods, such as seed treatment. This study aimed to assess glyphosate hormesis on growth rates and biomass accumulation in seedlings soybean cultivars. Two dose-response experiments [doses from 0 to 2880 g acid equivalent (ae) ha-1], one via foliar and one via seed, were conducted on three soybean cultivars [one non-glyphosate-resistant (NGR) and two glyphosate-resistant (GR, one RR and one RR2)]. In a subsequent experiment, three safe glyphosate doses (0, 90 and 180 g ae ha-1) applied via seed were evaluated on four soybean cultivars (two RR and two RR2). For foliar applications, the range of glyphosate doses increasing growth rates and dry biomass by 12-28 % were 5.6-45 g ae ha-1 for the NGR cultivar, of 45-720 g ae ha-1 for RR and of 11.25-180 g ae ha-1 for RR2. In the seed treatment, biomass increases of 16-60 % occurred at 45-180 g ae ha-1 for the NGR and RR cultivars, and 90-360 g ae ha-1 for RR2. Glyphosate doses of 90 and 180 g ae ha-1, applied via seeds, provided greater growth and biomass accumulation for the RR and RR2 soybean cultivars. Both foliar and seed applications of glyphosate increased growth and biomass accumulation in soybean cultivars, with seed treatments showing greater and more consistent enhancements. These findings propose practical and viable alternative for harnessing glyphosate hormesis to facilitate the early development of soybeans and potentially enhance crop yield.

Harnessing Brazilian biodiversity database: identification of flavonoids as potential inhibitors of SARS-CoV-2 main protease using computational approaches and all-atom molecular dynamics simulation.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the etiological agent responsible for the global outbreak of COVID-19 (Coronavirus Disease 2019). The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a vital role in mediating viral replication and transcription. In this study, a comprehensive computational approach was employed to investigate the binding affinity, selectivity, and stability of natural product candidates as potential new antivirals acting on the viral polyprotein processing mediated by SARS-CoV-2 Mpro. A library of 288 flavonoids extracted from Brazilian biodiversity was screened to select potential Mpro inhibitors. An initial filter based on Lipinski's rule of five was applied, and 204 compounds that did not violate any of the Lipinski rules were selected. The compounds were then docked into the active site of Mpro using the GOLD program, and the poses were subsequently re-scored using MM-GBSA (Molecular Mechanics Generalized Born Surface Area) binding free energy calculations performed by AmberTools23. The top five flavonoids with the best MM-GBSA binding free energy values were selected for analysis of their interactions with the active site residues of the protein. Next, we conducted a toxicity and drug-likeness analysis, and non-toxic compounds were subjected to molecular dynamics simulation and free energy calculation using the MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method. It was observed that the five selected flavonoids had lower MM-GBSA binding free energy with Mpro than the co-crystal ligand. Furthermore, these compounds also formed hydrogen bonds with two important residues, Cys145 and Glu166, in the active site of Mpro. Two compounds that passed the drug-likeness filter showed stable conformations during the molecular dynamics simulations. Among these, NuBBE_867 exhibited the best MM-PBSA binding free energy value compared to the crystallographic inhibitor. Therefore, this study suggests that NuBBE_867 could be a potential inhibitor against the main protease of SARS-CoV-2 and may be further examined to confirm our results.

Laparoscopic ureteroneocystostomy for ureteral injuries after hysterectomy.

OBJECTIVES: To examine the feasibility of early laparoscopic ureteroneocystostomy for ureteral obstruction due to hysterectomy injury. METHODS: We retrospectively reviewed a 10-y experience from 2 institutions in patients who underwent early (<30 d) or late (>30 d) laparoscopic ureteroneocystostomy for ureteral injury after hysterectomy. Evaluation of the surgery included the cause of the stricture and intraoperative and postoperative outcomes. RESULTS: A total of 9 patients with distal ureteral injury after hysterectomy were identified. All injuries were identified and treated as early as 21 d after hysterectomy. Seven of 9 patients underwent open hysterectomy, and the remaining patients had vaginal and laparoscopic radical hysterectomy. All ureteroneocystostomy cases were managed laparoscopically without conversion to open surgery and without any intraoperative complications. The Lich-Gregoir reimplantation technique was applied in all patients, and 2 patients required a psoas hitch. The mean operative time was 206.6 min (range, 120-280 min), the mean estimated blood loss was 122.2 cc (range, 25-350 cc), and the mean admission time was 3.3 d (range, 1-7 d). Cystography showed no urine leak when the ureteral stent was removed at 4 to 6 wk after the procedure. Ureteroneocystostomy patency was followed up with cystography at 6 mo and at least 10 y after ureteroneocystostomy. CONCLUSION: Early laparoscopic ureteral reimplantation may offer an alternative surgical approach to open surgery for the management of distal ureteral injuries, with favorable cosmetic results and recovery time from ureteral obstruction due to hysterectomy injury.

Laparoendoscopic single-site nephroureterectomy for morbid obese patients.

Since the first laparoendoscopic single-site (LESS) surgery report in urology in 2007 (1) (Rane A e Cadeddu JA), the few reports of LESS extraperitoneal access in the literature were mainly described for less complex cases. The aim of this video is to demonstrate the feasibility of LESS extraperitoneal access in a morbid obese patient presenting a malignant tumor in the renal pelvis. The patient is positioned in 90-degree lateral decubitus. An incision is made below the abdominal skin crease on the left side of the patient and the anterior rectus fascia is vertically incised with manual dissection of the extra/retroperitoneal space. We use an Alexis® retractor to retract the skin maximizing the incision orifice. Three trocars (12, 10 and 5 mm) are inserted through a sigle-port. The pedicle was controlled "en bloc" with a vascular stapler and the bladder cuff treated by the conventional open approach through the same incision. Operative time was 126 minutes with minimal blood loss. The pathology reported high grade papillary urothelial carcinoma in the pelvis (pT3N0M0) and in the ureter (pTa). LESS extraperitoneal nephroureterectomy is feasible and safe, even in more complex cases. It is a good alternative for morbid obese patients and for patients with synchronous distal ureteral tumors for whom an open approach to the bladder cuff is proposed to avoid incisions in two compartments of the abdominal wall.

Expanded criteria for video endoscopic inguinal lymphadenectomy (VEIL) in penile cancer: palpable lymph nodes.

INTRODUCTION: Open inguinal lymphadenectomy is the gold standard for the treatment of inguinal metastasis in patients with penile cancer (PC). Recently the Video Endoscopic Inguinal Lymphadenectomy (VEIL) was proposed as an option to reduce the morbidity of the procedure in patients without palpable inguinal lymph nodes (PILN), however the oncological equivalency in patients with PILN remains poorly studied. The aims of this video are the demonstration of VEIL in patients with PILN and present the preliminary experience comparing patients with and without PILN. MATERIALS AND METHODS: The video illustrates the procedure performed in two cases that were previously underwent partial penectomy for PC with PILN. Data from the series of 15 patients (22 limbs operated) with PILN underwent VEIL were compared with our series of VEIL in 25 clinically N0 patients (35 limbs operated). RESULTS: The comparison between the groups with and without PILN found, respectively, these outcomes: age 52,45 x 53,2 years, operative time 126,8 x 95,5 minutes, hospital stay 5. x 3.1 days, drainage time 6.7 x 5.7 days, 9 resected lymph nodes on average in both groups, global complications 32% x 26%, cellulitis 4.5% x 0%, lymphocele 23% in both groups, skin necrosis 0% x 3%, myocutaneous necrosis 4.5% x 0%, pN+ 33% x 32 %, cancer specific mortality 7 % x 5 % and mean follow-up 17.3 x 35.3 months. None of the variables presented p < 0.05. CONCLUSIONS: VEIL is a safe complementary procedure for treatment of PC, even in patients with PILN. Oncological results in patients with PILN seem to be appropriate but are still very premature. Prospective multicenter studies with larger samples and long-term follow-up should be conducted to determine the oncological equivalence of VEIL compared with open surgery in patients with PILN.

A history under construction: Manguinhos-Maré in the present time. / Uma história em construção: Manguinhos-Maré no tempo presente.

The two first decades of the twenty-first century were representative of the contemporary history of the Oswaldo Cruz Foundation (Fundação Oswaldo Cruz) and demonstrated its active role in the national health scenario. This article discusses the spatial transformations that took place in the territory occupied by the foundation from the year 2000 onward. The transformations in the use of this territory and it's institutional policy within the national context are described, along with the social demands that have impacted the institution, namely large-scale urban transformations and pandemics. This research uses the premises of the history of the present to investigate the changes that took place on the Manguinhos-Maré campus and in the discourse of the institutions involved in managing and planning these changes through analysis of institutional reports, digital mapping, and aerial images.

As duas primeiras décadas do século XXI foram representativas para a história contemporânea da Fundação Oswaldo Cruz e demonstraram seu protagonismo no cenário nacional da saúde. O artigo apresenta transformações espaciais ocorridas no território ocupado pela instituição a partir de 2000. Relacionam-se as transformações no uso dos territórios com sua política institucional no contexto nacional e são ressaltadas as demandas sociais que impactaram a instituição ­ transformações urbanas de grande porte e pandemias. O trabalho averigua, sob os pressupostos da história do tempo presente, as mudanças ocorridas no campus Manguinhos-Maré e no discurso de sujeitos institucionais gestores e projetistas. Para isso, conjuga análise dos relatórios institucionais, da base digital cartográfica e de imagens aéreas.

Hormetic Effect of Glyphosate on the Morphology, Physiology and Metabolism of Coffee Plants.

Glyphosate is a nonselective herbicide of systemic action that inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthase, thus compromising amino acid production and consequently the growth and development of susceptible plants. The objective of this study was to evaluate the hormetic effect of glyphosate on the morphology, physiology, and biochemistry of coffee plants. Coffee seedlings (Coffea arabica cv Catuaí Vermelho IAC-144) were transplanted into pots filled with a mixture of soil and substrate and subjected to ten doses of glyphosate: 0, 11.25, 22.5, 45, 90, 180, 360, 720, 1440, and 2880 g acid equivalent (ae) ha-1. Evaluations were performed using the morphological, physiological, and biochemical variables. Data analysis for the confirmation of hormesis occurred with the application of mathematical models. The hormetic effect of glyphosate on coffee plant morphology was determined by the variables plant height, number of leaves, leaf area, and leaf, stem, and total dry mass. Doses from 14.5 to 30 g ae ha-1 caused the highest stimulation. In the physiological analyses, the highest stimulation was observed upon CO2 assimilation, transpiration, stomatal conductance, carboxylation efficiency, intrinsic water use efficiency, electron transport rate, and photochemical efficiency of photosystem II at doses ranging from 4.4 to 55 g ae ha-1. The biochemical analyses revealed significant increases in the concentrations of quinic acid, salicylic acid, caffeic acid, and coumaric acid, with maximum stimulation at doses between 3 and 140 g ae ha-1. Thus, the application of low doses of glyphosate has positive effects on the morphology, physiology, and biochemistry of coffee plants.

Applications of Artificial Intelligence and Radiomics in Molecular Hybrid Imaging and Theragnostics for Neuro-Endocrine Neoplasms (NENs).

Nuclear medicine has acquired a crucial role in the management of patients with neuroendocrine neoplasms (NENs) by improving the accuracy of diagnosis and staging as well as their risk stratification and personalized therapies, including radioligand therapies (RLT). Artificial intelligence (AI) and radiomics can enable physicians to further improve the overall efficiency and accuracy of the use of these tools in both diagnostic and therapeutic settings by improving the prediction of the tumor grade, differential diagnosis from other malignancies, assessment of tumor behavior and aggressiveness, and prediction of treatment response. This systematic review aims to describe the state-of-the-art AI and radiomics applications in the molecular imaging of NENs.