Antihistamines H1 as Potential Anthelmintic Agents against the Zoonotic Parasite Angiostrongylus cantonensis.

Infections caused by parasitic helminths pose significant health concerns for both humans and animals. The limited efficacy of existing drugs underscores the urgent need for novel anthelmintic agents. Given the reported potential of antihistamines against various parasites, including worms, this study conducted a screening of clinically available antihistamines against Angiostrongylus cantonensis-a nematode with widespread implications for vertebrate hosts, including humans. Twenty-one anti-H1 antihistamines were screened against first-stage larvae (L1) of A. cantonensis obtained from the feces of infected rats. Standard anthelmintic drugs ivermectin and albendazole were employed for comparative analysis. The findings revealed four active compounds (promethazine, cinnarizine, desloratadine, and rupatadine), with promethazine demonstrating the highest potency (EC50 = 31.6 µM). Additionally, morphological analysis showed that antihistamines induced significant changes in larvae. To understand the mechanism of action, antimuscarinic activities were reported based on average pK i values for human muscarinic receptor (mAChR) subtypes of the evaluated compounds. Furthermore, an analysis of the physicochemical and pharmacodynamic properties of antihistamines revealed that their anthelmintic activity does not correlate with their activity at H1 receptors. This study marks the first documentation of antihistamines' activity against A. cantonensis, offering a valuable contribution to the quest for novel agents effective against zoonotic helminths.

Ketamine versus electroconvulsive therapy for major depressive episode: An updated systematic review and non-inferiority meta-analysis.

We conducted a systematic review and meta-analysis to investigate the comparative effectiveness of ketamine versus electroconvulsive therapy (ECT) for the treatment of major depressive episodes (MDEs). PubMed, EMBASE and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) comparing ketamine and ECT for MDE. The primary outcome was response rate, for which we prespecified a non-inferiority margin of -0.1, based on the largest and most recent RCT. Response was defined as a reduction of at least 50 % in the depression scale score. Six RCTs met the inclusion criteria, comprising 655 patients. In the overall population, ketamine was not non-inferior to ECT in response rate (RD -0.10; 95 % CI -0.26 to 0.05; p = 0.198; I2 = 72 %). The ECT group had a higher reduction in depression scores, but without difference in remission and relapse rates. Regarding safety outcomes, ketamine had better posttreatment cognition scores and reduced muscle pain rate compared with ECT, albeit with an increased rate of dissociative symptoms. In a subanalysis with only inpatients, ketamine was inferior to ECT in response rate (RD -0.15; 95 % CI -0.27 to -0.03; p = 0.014; I2 = 25 %), remission, and change in depression scores. These findings support the use of ECT over ketamine for inpatients. Further RCTs are warranted to clarify the comparative effect of these treatments for outpatients.

The histamine H4 receptor antagonist 1-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)methyl]-4-methyl-piperazine(LINS01007) prevents the development of DSS-induced colitis in mice.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with growing incidence worldwide. Our group reported the compound 5-choro-1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine (LINS01007) as H4R antagonist (pKi 6.2) and therefore the effects and pharmacological efficacy on a DSS-induced mice model of UC were assessed in this work. Experimental acute colitis was induced in male BALB/c mice (n = 5-10) by administering 3 % DSS in the drinking water for six days. The test compound LINS01007 was administered daily i.p. (5 mg/kg) and compared to control group without treatment. Body weight, water and food consumption, and the presence of fecal blood were monitored during 7-day treatment period. The levels of inflammatory markers (PGE2, COX-2, IL-6, NF-κB and STAT3) were also analyzed. Animals subjected to the acute colitis protocol showed a reduction in water and food intake from the fourth day (p < 0.05) and these events were prevented by LINS01007. Histological signs of edema, hyperplasia and disorganized intestinal crypts, as well as neutrophilic infiltrations, were found in control mice while these findings were significantly reduced in animals treated with LINS01007. Significant reductions in the levels of PGE2, COX-2, IL-6, NF-κB and STAT3 were observed in the serum and tissue of treated animals. The results demonstrated the significant effects of LINS01007 against DSS-induced colitis, highlighting the potential of H4R antagonism as promising treatment for this condition.

Morphological analysis of the jugular foramen in dry human skulls in northeastern Brazil.

The jugular foramen (JF) is located between the temporal and occipital bones. The JF is a primary pathway for venous outflow from the skull and passage of nerves. Variations are common in this region and may have clinical and surgical implications. To analyze the sexual dimorphism and JF morphology in skulls from Northeastern Brazil. 128 human skulls from the Anatomy Laboratory of the Federal University of Paraíba, 64 male and 64 female, were selected and the JFs analyzed for bone septation and the presence of a dome. Data analysis considered P<0.05 as significant. On at least one side, complete septation was observed in 26 skulls (20.3%), incomplete septation in 93 skulls (72.6%) and 61 skulls (47.6%) did not present septation. In 114 skulls (89%), 47.6% female and 41.4% male, have a unilateral presence of the dome and 71 (55.4%) have it bilaterally. Posterolateral compartment diameters and JF area had higher values on the right side in the total sample and separated by sex (P<0.05). Most morphometric variables of the anteromedial compartment were higher in male than in female (P<0.05), fact that was not observed in the posterolateral compartment (P>0.05). This study showed a higher prevalence of complete septation in males compared to females. Morphometric analysis presented a peculiar morphology of the JF in this study. These results suggests that the surgical approach to diseases that affect the JF may be peculiar to the studied population, confirming the importance of morphological analysis of the skull base.

Clinical and thermographic evaluation after lower third molar extractions and the application of different photobiomodulation protocols: double-blind randomised clinical trial.

OBJECTIVES: to compare the parameters of pain, oedema, temperature, and soft tissue closure in dental sockets that received two different photobiomodulation (PBM) protocols following extractions. MATERIALS AND METHODS: Thirty-one participants had their teeth 38 and 48 extracted. Subsequently, one of the dental sockets received PBM at a wavelength (WL) of 808 nanometers (808 group- nm) and the other dental socket received the PBM at WLs of 808 nm and 660 nm, simultaneously (808 + 660 group). The PBM was applied immediately after the surgical procedure and on the 3rd and 7th days. RESULTS: The mean of Visual Analogue Scale (VAS) values for pain were 1.45 for the 3rd day and 0.52 for the 7th day in the 808 + 660 and 808 group, respectively. The mean the pogonion-tragus measurement, used to assess facial oedema on the 3rd day, was 15.38 cm (range 13.5-17.5) in the 808 + 660 group and 15.48 cm (range 14.0-17.5) in the 808 group. The mean facial temperatures in the 808 + 660 group were 34.9 degrees Celsius (ºC) (range 33.5-36.4) on the 3rd day and 35 ºC (range 33.4-36.4) on the 7th day. In the 808 group, the mean temperatures were 34.9 ºC (range 33.9-36.2) on the 3rd day and 34.9 ºC (33.7-36.2) on the 7th day. Regarding the dimensions of the dental socket, the mean were similar for both groups. Significant differences between the groups were only observed in the pain parameter and only on the 7th day, being greater for the 808 + 660 group (p = 0.031). CONCLUSIONS: The association of the 660 nm with 808 nm, and the increase in energy did not showed more benefits in pain reduction oedema, or acceleration of the closure of the soft tissues of the dental sockets of lower third molars, in the protocols used here. CLINICAL RELEVANCE: There is no need to combine lasers at wavelengths of 660 and 808 nm to reduce oedema, pain and repair of soft tissues after extraction of lower third molars. CLINICAL TRIAL REGISTRATION: This trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) with the following code: RBR-66pyrh8, on 29th December, 2022.

Antioxidant activity of an Mg(II) compound containing ferulic acid as a chelator: potential application for active packaging and riboflavin stabilisation.

Foods rich in riboflavin (Rf) are susceptible to degradation due to oxidative processes with the formation of radicals. Herein, we describe the features and stability of an Mg(II) complex containing ferulic acid (fer) and 1,10-phenanthroline (phen) as chelators: henceforth called Mg(phen)(fer). The electrochemical behavior of Mg(phen)(fer) is pH dependent and results from the stabilisation of the corresponding phenoxyl radical via complexation with Mg(II). This stabilisation enhances the antioxidant activity of Mg(phen)(fer) with respect to free fer and commercial antioxidants. Mg(phen)(fer) scavenges and neutralizes DPPH˙ (IC50 = 15.6 µmol L-1), ABTS˙+ (IC50 = 5.65 µmol L-1), peroxyl radical (IC50 = 5.64 µg L-1) and 1O2 (IC50 = 0.7 µg m-1). Mg(phen)(fer) effectively protects riboflavin (Rf) against photodegradation by quenching the singlet excited states of Rf regardless of the conditions. Also, the complex Mg(phen)(fer) was effectively incorporated into starch films, broadening its applications, as shown by microbiological studies. Thus, Mg(phen)(fer) has high potential for use in Rf-rich foods and to become a new alternative to the synthetic antioxidants currently used.

Effect of digestible protein on intermediate metabolism, hepatic enzyme activities, energy reserves, and growth performance of pacu (Piaractus mesopotamicus) in the finishing growth phase.

This study investigated the effect of different levels of digestible protein (DP) on blood metabolites, hepatic enzyme activity of glycolysis and amino acid metabolism, energy reserves, and the production characteristics of pacu (Piaractus mesopotamicus) during the finishing growth phase. Six semi purified and isoenergetic diets, containing 16.3, 20.1, 23.8, 27.2, 31.5, and 34.8% of balanced DP, provided with essential amino acid balance, were hand-fed to pacu (1100.0 ± 10.3 g, initial weight) three times daily for 7 weeks. The experiment consisted of six treatments, with three randomly arranged replicates (tanks) per treatment. The data obtained from this experiment were analyzed by one-way analysis of variance (ANOVA), and significant differences (p < 0.05) between treatments were determined using Tukey's test. Blood metabolites, except serum ammonia and the hepatic enzymes activities of glycolysis and amino acid metabolism, except hexokinase activity were affected (p < 0.05) by balanced DP. The energy reserve indices, except hepatic total lipid content, were also found associated (p < 0.05) with balanced DP. The test diets significantly (p < 0.05) affected growth performance parameters. Higher dietary proteins led to a greater energy uptake by fish from the protein in feed. Overall, fish fed the intermediate level (23.8%) of balanced DP with digestible energy of 17.95 MJ kg-1 showed better production traits and physio-biochemical health markers. This information could help nutritionists and farmers to develop nutritionally balanced and economically and environmentally sustainable aquafeed for promoting healthy and sustainable production of pacu in intensive culture systems.

Optimised return to play: high treatment success rate in core muscle injury with surgical release of the anterior tendon of the rectus abdominis muscle and proximal tenotomy of the adductor longus muscle.

OBJECTIVES: Core muscle injury is a debilitating condition that causes chronic groin pain in athletes, particularly common in soccer players. The condition is characterised by pain in the inguinal region and can lead to a significant number of absences from high-intensity physical activity. It is caused by repetitive overload without proper counterbalance from the abdominal muscles, hip flexors, and adductors in susceptible athletes. Surgical indications for core muscle injury consider cases where non-surgical treatments have not provided sufficient relief. The aim of this study was to assess the results of surgical intervention for core muscle injury using the technique employed by the Sports Medicine Group of (Institute of Orthopedics and Traumatology of Hospital das Clínicas - Universidade de São Paulo). The procedure involves releasing the anterior portion of the tendon of the rectus abdominis muscle near the pubic symphysis, along with proximal tenotomy of the adductor longus muscle tendon. METHODS: This study utilised a consecutive historical cohort analysis of the medical records of 45 male athletes, of which, 75.6% were professional soccer players, who underwent surgical treatment between January 1, 2002, and December 31, 2021. The participants included active athletes aged between 18 and 40 years, with a mean age of 23.9 years, and were diagnosed with myotendinous core muscle injury. These athletes experienced pain in the pubic symphysis and adductor tendon region and had previously undergone medical treatment and physical therapy for a duration of three to six months without significant improvement. RESULTS: The average time for athletes to return to sport after surgery was 135 days, with a majority of participants being soccer and futsal players. The surgical intervention yielded promising results, with a positive correlation between unilateral injuries and the time taken to return to sport. The complication rate was low, at 6.7%. Notably, the rate of symptom resolution was high, at 93.3%. Furthermore, the analysis indicated that the player's position on the field significantly influenced the discharge period, suggesting that the game position plays a role in the recovery process. CONCLUSION: The combined surgical procedure involving the release of the rectus abdominis tendon and adductor longus muscle tenotomy demonstrates favourable outcomes for athletes with core muscle injury. This study provides strong support for the effectiveness of this surgical approach in managing the condition and offers a potential path to recovery and return to sports activities. STUDY DESIGN: Cross-sectional study.

Is melatonin as an ergogenic hormone a myth? a systematic review and meta-analysis.

PURPOSE: Melatonin supplementation has been disclosed as an ergogenic substance. However, the effectiveness of melatonin supplementation in healthy subjects has not been systematically investigated. The present study analyzed the effects of melatonin supplementation on physical performance and recovery. In addition, it was investigated whether exercise bout or training alter melatonin secretion in athletes and exercise practitioners. METHODS: This systematic review and meta-analysis were conducted and reported according to the guidelines outlined in the PRISMA statement. Based on the search and inclusion criteria, 21 studies were included in the systematic review, and 19 were included in the meta-analysis. RESULTS: Melatonin supplementation did not affect aerobic performance relative to time trial (-0.04; 95% CI: -0.51 to 0.44) and relative to VO2 (0.00; 95% CI: -0.57 to 0.57). Also, melatonin supplementation did not affect strength performance (0.19; 95% CI: -0.28 to 0.65). Only Glutathione Peroxidase (GPx) secretion increased after melatonin supplementation (1.40; 95% CI: 0.29 to 2.51). Post-exercise melatonin secretion was not changed immediately after an exercise session (0.56; 95% CI: -0.29 to 1.41) and 60 min after exercise (0.56; 95% CI: -0.29 to 1.41). CONCLUSION: The data indicate that melatonin is not an ergogenic hormone. In contrast, melatonin supplementation improves post-exercise recovery, even without altering its secretion.

Espiritualidade e religiosidade na prática médica em um hospital universitário / Spirituality and religiosity in medical practice at a university hospital / Espiritualidad y religiosidad en la práctica médica en un hospital universitario

Resumo A religiosidade e a espiritualidade desempenham papéis cruciais na medicina, especialmente na abordagem centrada no paciente, melhorando a relação médico-paciente. Apesar disso, muitos médicos ainda subutilizam esses recursos, muitas vezes devido a insegurança ao lidar com a esfera pessoal da vida dos pacientes. Para abordar essa questão, conduziu-se pesquisa com 128 médicos, incluindo residentes, em um hospital universitário de Minas Gerais, entre agosto e dezembro de 2021, mediante aplicação dos questionários Inventário de Religiosidade de Duke e Escala Multidimensional de Reatividade Interpessoal, além de questões levantadas em estudos anteriores sobre saúde e espiritualidade. Com isso, buscou-se avaliar de que forma profissionais percebem a importância da religiosidade e da espiritualidade na prática clínica e sua relação com posturas éticas e humanistas. Os resultados revelaram correlação significativa entre as duas escalas, indicando associação positiva entre religiosidade e espiritualidade e empatia.

Abstract Religiosity and spirituality are pivotal in medical practice, particularly in fostering a patient-centered approach that enhances the physician-patient relationship. Despite this, many physicians still underutilize these invaluable resources, often due to feelings of uncertainty when navigating the personal aspects of patients' lives. To address this challenge, a survey involving 128 physicians, including residents, was conducted at a university hospital in Minas Gerais between August and December 2021. Utilizing the Duke Religiosity Inventory and Multidimensional Interpersonal Reactivity Scale questionnaires, alongside inquiries drawn from prior studies on health and spirituality, the goal was to assess professionals' perceptions of the significance of religiosity and spirituality in clinical practice and their interplay with ethical and humanistic attitudes. The findings unveiled a significant correlation between the two scales, underscoring a positive connection between religiosity, spirituality, and empathy.

Resumen La religiosidad y la espiritualidad desempeñan un papel clave en la medicina, especialmente en el enfoque centrado en el paciente al mejorar la relación médico-paciente. Muchos médicos aún no utilizan este recurso, debido a la inseguridad a menudo de enfrentar la vida personal de los pacientes. En este estudio se aplicó a 128 médicos y residentes de un hospital universitario de Minas Gerais (Brasil) los cuestionarios Índice de Religiosidad de Duke y Índice de Reactividad Interpersonal Multidimensional entre agosto y diciembre de 2021, así como preguntas planteadas en estudios anteriores sobre salud y espiritualidad. Se pretendió evaluar la percepción de los profesionales sobre la importancia de la religiosidad y la espiritualidad en la práctica clínica y su relación con las actitudes éticas y humanistas. Los resultados revelaron una correlación significativa entre las dos escalas, lo que indica una asociación positiva entre la religiosidad y espiritualidad y la empatía.

Standardization of the Radiographic Study of the Foot Using the Niza Box.

Objective This study proposes the Niza box, a device created to reduce interpretive errors among professionals and facilitate the correct positioning of structures by standardizing orthopedic radiography of the foot in anteroposterior, loaded, and Saltzman views. Methods Descriptive study based on material collected at an Orthopedics Ambulatory from a tertiary service in a large Brazilian city. The X-ray device was a Lotus X, model HF 500 M, 500 milliamperes and 125 kilovolts capacity, 100 cm focus-film distance, and 24 × 30 cm radiographic chassis. Device controls were set at 100 mA, 5 mA/sec, and 60 kilovolts, depending on the variable size of the foot. The same team of previously trained radiography technicians performed the tests under the authors' supervision. The chassis were positioned in three specific Niza box spaces per the proposed incidence. Data from 50 images from people between 18 and 70 years old were analyzed. Results Radiographs taken using the proposed device usually had a satisfactory quality, allowing correct identification of the anatomical elements of the foot and ankle and angular reconstruction. Small image variations due to foot size were acceptable and expected, allowing radiograph standardization. Conclusion The Niza box is a good method for minimizing interference and avoiding radiographic interpretation errors, providing quality and agility to the examination, and reducing cost and unnecessary repetitions. It is an innovative, low-cost device made of recyclable and biodegradable material.

Investigation of Structure-Activity Relationships for Benzoyl and Cinnamoyl Piperazine/Piperidine Amides as Tyrosinase Inhibitors.

Melanin is a substance that plays important roles in several organisms. Its function as an antioxidant and metal-complexing agent makes tyrosinase, the key enzyme that controls melanogenesis, an interesting target for designing inhibitors. In this article, we report a set of piperazine/piperidine amides of benzoic and cinnamic acid derivatives as tyrosinase inhibitors with improved potency and drug-likeness. The most potent compound 5b showed a pIC50 of 4.99 in the monophenolase assay, and only compound 3a showed reasonable potency in the diphenolase assay (pIC50, 4.18). These activities are not correlated to antiradical activity, suggesting that the activity is dependent on competition with the substrates. Molecular docking studies indicated that the benzyl substituent of 5b and other analogues perform important interactions in the enzyme that may explain the higher potency of these compounds. Moreover, the compounds present adequate lipophilicity and skin permeability and no relevant cytotoxicity (CC50 > 200 µM) to mammalian cells.

First report of root-knot nematode, Meloidogyne javaniva, infecting Stachys byzantina on São Paulo, Brazil.

Stachys byzantina belongs to the Labiatae and is known by the names "peixinho-da-horta" (Brazil) and "lamb's ear" (USA). Its importance is associated with its medicinal properties (Bahadori et al. 2020) and nutritional aspects (Milião et al. 2022). Root-knot nematodes cause severe damage to plants and suppress production. In January 2021, plants of S. byzantina in the municipality of Jaboticabal (21°14'38.7"S, 48°17'10.6"W) showed symptoms of reduced growth, yellowed leaves and the presence of galls in the roots. Initially, samples of roots from a S. byzantina were analyzed at the Nematology Laboratory (LabNema/UNESP), Jaboticabal, Brazil, estimating 20,000 eggs and juveniles of Meloidogyne sp. in 10 g of roots. To confirm the host ability of the species, a pathogenicity test was performed using Koch's postulate. For this purpose, the test was conducted in a greenhouse where 3,000 eggs and second-stage juveniles (J2) were inoculated onto three plants (n=3) of S. byzantina. After 90 days, the inoculated plants showed the same symptoms as those observed in the field. No symptom or nematode was detected in the uninoculated plant (control). Nematodes were extracted from the roots of inoculated plants and quantified. The perineal pattern of females (n=10) (Netscher and Taylor, 1974) and the labial region of males (n=10) (Eisenback and Hirschmann, 1981) were analyzed and compared with the morphological characteristics of the original description of the species (Chitwood, 1949). For analysis based on esterase isozyme phenotype, the α-method of Esbenshade and Triantaphyllou (1990) was used, and females (n=7) were examined. To confirm identification, whole genomic DNA from an adult female (n=1) was extracted using the Qiagen DNeasy® Blood & Tissue Kit and this sample was used for both genetic sequencing and the sequence-characterized amplified region techniques (SCAR). PCR amplifications were performed for the 18s rRNA gene using primers 988F and 1912R from Holterman et al (2006). Our sequence was deposited in GenBank (NCBI) under the identifier OP422209. Finally, species-specific SCAR primers (Fjav/Rjav, Me-F/Me-R, and Finc-F/Finc-R) designed by Zijlstra (2000) were used to identify Meloidogyne spp. Koch's postulate analysis yielded the following results: (n=1) 9,280 eggs and J2 (Reproduction factor, RF = 33.09); (n=2) 111,720 eggs and J2 (RF = 37.24); (n=3) 59,700 eggs and J2 (RF = 19.9) (RF mean = 30.08). The following characteristics were observed in the perineal region of females: Low and rounded trapezoidal dorsal arch with two distinct lateral lines clearly separating the dorsal and ventral arch regions, similar to the morphological features of the species description by Chitwood (1949). Males had a convex labial plate with a non-raised labial disk joining the submedial labia, a non-rugged labial region, the basal tubercles were usually wider than high, and a rounded tail tip (Eisenback and Hirschmann 1981). The α-esterase enzyme profile showed the J3 phenotype typical of M. javanica (Rm [×100] = 46.0, 54.5, and 58.9). The 18s rRNA sequences grouped Meloidogyne sp. with species such as M. enterolobii, M. incognita, and M. javanica. A DNA fragment of about 700 bp was amplified with Mj (Fjav/Rjav) primers, but not with Me (Me-F/Me-R) and Mi (Finc-F/Finc-R) primers, which confirmed the identification of M. javanica. Accurate identification and characterization of the occurrence of new hosts of M. javanica will allow us to determine the range and geographic distribution of the species. This is the first report on the occurrence of M. javanica on S. byzantina in Brazil. This report is important so that management strategies can be applied to prevent the spread of the pest to other areas.

Piperazine amides with desirable solubility, physicochemical and drug-like properties: Synthesis and evaluation of the anti-Trypanosoma cruzi activity.

The absence of effective chronic treatment, expansion to non-endemic countries and the significant burden in public health have stimulated the search for novel therapeutic options to treat Chagas disease, a protozoan disease caused by Trypanosoma cruzi. Despite current efforts, no new drug candidates were approved in clinical trials in the past five decades. Considering this, our group has focused on the expansion of a series (LINS03) with low micromolar activity against amastigotes, considering the optimization of pharmacokinetic properties through increasing drug-likeness and solubility. In this work, we report a new set of 13 compounds with modifications in both the arylpiperazine and the aromatic region linked by an amide group. Five analogues showed activity against intracellular amastigotes (IC50 17.8 to 35.9 µM) and no relevant cytotoxicity to mammalian cells (CC50 > 200 µM). Principal component analysis (PCA) was performed to identify structural features associated to improved activity. The data revealed that polarity, hydrogen bonding ability and flexibility were key properties that influenced the antiparasitic activity. In silico drug-likeness assessments indicated that compounds with the 4-methoxycinammyl (especially compound 2b) had the most prominent balance between properties and activity in the series, as confirmed by SAR analysis.

How well are Brazilian mastologists (breast surgeons) trained in breast reconstruction and oncoplastic surgery? A study of the impact of a breast reconstruction and oncoplastic surgery improvement course.

Introduction: The breasts are a female symbol, impacts self-image and self-esteem. Breast reconstructive and oncoplastic surgeries have an important role in minimizing injuries. In Brazil less than a third of public health system (SUS) users have access to immediate reconstructive surgery. The low rate of breast reconstructions has multiple causes and the deficiency in availability and surgeons' technical qualification play a role. In 2010, the Breast Reconstruction and Oncoplastic Surgery Improvement Course was created by professors of the Mastology Department of Santa Casa de São Paulo and State University of Campinas (UNICAMP). The objectives of this study were to evaluate the impact of the techniques learned on patients' management by the surgeons enrolled in the Course, as well as to characterize their profile. Methods: All students enrolled in the Improvement Course between 2010 and 2018 were invited to answer an online questionnaire. Students who did not agree to answer the questionnaire or answered them incompletely were excluded. Results: Total students included: 59. The mean age: 48.9 years, male (72%) with more than 5 years of Mastology practice (82.2%), from all regions of Brazil, 1.7% from the North, 33.9% from the Northeast, 44.1% from the Southeast, and 12% from the South. Most of the students considered they had little or no knowledge of breast reconstruction (74.6%) and 91,5% did not consider they had enough aptitude to perform breast reconstructions after finishing residency. After the Course, 96.6% considered themselves apt to perform such surgeries. Over 90% of the students considered the Course had impacted their practice and changed their surgical strategy view. Before the Course, 84.8% of the students stated that less than half of their patients who were operated on for breast cancer had breast reconstruction, compared to 30.5% after the Course. Conclusion: The Breast Reconstruction and Oncoplastic Surgery Improvement Course studied here positively impacted the mastologists' management of patients. New training centers worldwide can help a lot of women with breast cancer.

Cannabinoids for Substance Use Disorder Treatment: What Does the Current Evidence Say?

Background: The prevalence of Substance Use Disorder (SUD) is increasing along with the need to develop approaches to reduce the harm associated with substance use, including investigating alternatives such as cannabinoids, which show promising results, although the current evidence is limited. This scoping review focuses on the limitations and potentials of cannabinoid-based treatments for SUDs. Methods: We examined between-subject randomized controlled trials (RCTs) investigating the use of CBD and THC as pharmacological treatment for SUDs in adults, with the procedures attending the expectations of the Preferred Reporting Items for Scoping reviews and Meta-Analyses (PRISMA) for Scoping Reviews guidelines and assessed risk of bias using the Cochrane Risk of Bias Assessment Tool 2. Results: Ten RCTs were included, with six demonstrating low risk of bias, and positive results were found for treating Cannabis Use Disorder, while contradictory results were found for Opioid Use Disorder, and inconclusive results for treating Cocaine Use Disorder. Conclusions: CBD and THC demonstrate potential for treating some SUDs, but evidence is limited. Robust RCTs with larger samples and longer follow-up periods are necessary to assess carefully developed outcomes for different SUD patients. New cannabinoid-based medications and scientific-based policies may advance SUD treatment. A comprehensive approach to treatment and careful methodological choices may benefit patients with SUD.

Risk prediction in patients with classical low-flow, low-gradient aortic stenosis undergoing surgical intervention.

Introduction: Classical low-flow, low-gradient aortic stenosis (LFLG-AS) is an advanced stage of aortic stenosis, which has a poor prognosis with medical treatment and a high operative mortality after surgical aortic valve replacement (SAVR). There is currently a paucity of information regarding the current prognosis of classical LFLG-AS patients undergoing SAVR and the lack of a reliable risk assessment tool for this particular subset of AS patients. The present study aims to assess mortality predictors in a population of classical LFLG-AS patients undergoing SAVR. Methods: This is a prospective study including 41 consecutive classical LFLG-AS patients (aortic valve area ≤1.0 cm2, mean transaortic gradient <40 mmHg, left ventricular ejection fraction <50%). All patients underwent dobutamine stress echocardiography (DSE), 3D echocardiography, and T1 mapping cardiac magnetic resonance (CMR). Patients with pseudo-severe aortic stenosis were excluded. Patients were divided into groups according to the median value of the mean transaortic gradient (≤25 and >25 mmHg). All-cause, intraprocedural, 30-day, and 1-year mortality rates were evaluated. Results: All of the patients had degenerative aortic stenosis, with a median age of 66 (60-73) years; most of the patients were men (83%). The median EuroSCORE II was 2.19% (1.5%-4.78%), and the median STS was 2.19% (1.6%-3.99%). On DSE, 73.2% had flow reserve (FR), i.e., an increase in stroke volume ≥20% during DSE, with no significant differences between groups. On CMR, late gadolinium enhancement mass was lower in the group with mean transaortic gradient >25 mmHg [2.0 (0.0-8.9) g vs. 8.5 (2.3-15.0) g; p = 0.034), and myocardium extracellular volume (ECV) and indexed ECV were similar between groups. The 30-day and 1-year mortality rates were 14.6% and 43.8%, respectively. The median follow-up was 4.1 (0.3-5.1) years. By multivariate analysis adjusted for FR, only the mean transaortic gradient was an independent predictor of mortality (hazard ratio: 0.923, 95% confidence interval: 0.864-0.986, p = 0.019). A mean transaortic gradient ≤25 mmHg was associated with higher all-cause mortality rates (log-rank p = 0.038), while there was no difference in mortality regarding FR status (log-rank p = 0.114). Conclusions: In patients with classical LFLG-AS undergoing SAVR, the mean transaortic gradient was the only independent mortality predictor in patients with LFLG-AS, especially if ≤25 mmHg. The absence of left ventricular FR had no prognostic impact on long-term outcomes.

Multimodality imaging methods and systemic biomarkers in classical low-flow low-gradient aortic stenosis: Key findings for risk stratification.

Objectives: The aim of the present study is to assess multimodality imaging findings according to systemic biomarkers, high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, in low-flow, low-gradient aortic stenosis (LFLG-AS). Background: Elevated levels of BNP and hsTnI have been related with poor prognosis in patients with LFLG-AS. Methods: Prospective study with LFLG-AS patients that underwent hsTnI, BNP, coronary angiography, cardiac magnetic resonance (CMR) with T1 mapping, echocardiogram and dobutamine stress echocardiogram. Patients were divided into 3 groups according to BNP and hsTnI levels: Group 1 (n = 17) when BNP and hsTnI levels were below median [BNP < 1.98 fold upper reference limit (URL) and hsTnI < 1.8 fold URL]; Group 2 (n = 14) when BNP or hsTnI were higher than median; and Group 3 (n = 18) when both hsTnI and BNP were higher than median. Results: 49 patients included in 3 groups. Clinical characteristics (including risk scores) were similar among groups. Group 3 patients had lower valvuloarterial impedance (P = 0.03) and lower left ventricular ejection fraction (P = 0.02) by echocardiogram. CMR identified a progressive increase of right and left ventricular chamber from Group 1 to Group 3, and worsening of left ventricular ejection fraction (EF) (40 [31-47] vs. 32 [29-41] vs. 26 [19-33]%; p < 0.01) and right ventricular EF (62 [53-69] vs. 51 [35-63] vs. 30 [24-46]%; p < 0.01). Besides, there was a marked increase in myocardial fibrosis assessed by extracellular volume fraction (ECV) (28.4 [24.8-30.7] vs. 28.2 [26.9-34.5] vs. 31.8 [28.9-35.5]%; p = 0.03) and indexed ECV (iECV) (28.7 [21.2-39.1] vs. 28.8 [25.4-39.9] vs. 44.2 [36.4-51.2] ml/m2, respectively; p < 0.01) from Group 1 to Group 3. Conclusions: Higher levels of BNP and hsTnI in LFLG-AS patients are associated with worse multi-modality evidence of cardiac remodeling and fibrosis.

Postoperative myocardial fibrosis assessment in aortic valvular heart diseases-a cardiovascular magnetic resonance study.

AIMS: Left ventricular remodelling occurs during the chronic course of aortic regurgitation (AR) and aortic stenosis (AS), leading to myocardial hypertrophy and fibrosis. Several studies have shown that extracellular volume fraction (ECV) and indexed extracellular volume (iECV) are important surrogate markers of diffuse myocardial fibrosis (MF). Postoperative data on these cardiovascular magnetic resonance (CMR) extracellular expansion parameters for either AS or AR are scarce. This study aimed to demonstrate the postoperative changes that occur in diffuse MF, and the influence of preoperative MF on the reversal of LV remodelling, in patients with AR or AS. METHODS AND RESULTS: Patients with severe AR or AS and indications for surgery were prospectively enrolled. Patients underwent pre- and postoperative CMR, and ECV and iECV were quantified. Data from 99 patients were analysed (32 with AR and 67 with AS). After surgery, the left ventricle mass index decreased in both groups (AR: 110 vs. 91 g/m2; AS: 86 vs. 68 g/m2, both P < 0.001). The late gadolinium enhancement fraction (AR: preoperative 1.9% vs. postoperative 1.7%, P = 0.575; AS: preoperative 2.4% vs. postoperative 2.4%, P = 0.615) and late gadolinium enhancement mass (AR: preoperative 3.8 g vs. postoperative 2.5 g, P = 0.635; AS: preoperative 3.4 g vs. postoperative 3.5 g, P = 0.575) remained stable in both groups. Preoperative iECV and ECV were greater in the AR group (iECV: 30 mL/m2 vs. 22 mL/m2, P = 0.001; ECV: 28.4% vs. 27.2%, P = 0.048). Indexed extracellular volume decreased after surgery in both groups (AR: 30-26.5 mL/m2, AS: 22-18.2 mL/m2, both P < 0.001); it was still greater in the AR group (AR: 26.5 mL/m2 vs. AS: 18.2 mL/m2, P < 0.001). Postoperative ECV remained stable in the AR group (preoperative 28.4% vs. postoperative 29.9%; P = 0.617) and increased in the AS group (preoperative 27.2% vs. postoperative 28.6%; P = 0.033). CONCLUSION: Patients with both AR or AS presented reduction in iECV after surgery, unfolding the reversible nature of diffuse MF. In contrast to patients with AS, those with AR developed postoperative iECV regression with stable ECV, suggesting a balanced reduction in both intracellular and extracellular myocardial components.

Synthetic Analogues of Gibbilimbol B Induce Bioenergetic Damage and Calcium Imbalance in Trypanosoma cruzi.

Chagas disease is an endemic tropical disease caused by the protozoan Trypanosoma cruzi, which affects around 7 million people worldwide, mostly in development countries. The treatment relies on only two available drugs, with severe adverse effects and a limited efficacy. Therefore, the search for new therapies is a legitimate need. Within this context, our group reported the anti-Trypanosoma cruzi activity of gibbilimbol B, a natural alkylphenol isolated from the plant Piper malacophyllum. Two synthetic derivatives, LINS03018 (1) and LINS03024 (2), demonstrated a higher antiparasitic potency and were selected for mechanism of action investigations. Our studies revealed no alterations in the plasma membrane potential, but a rapid alkalinization of the acidocalcisomes. Nevertheless, compound 1 exhibit a pronounced effect in the bioenergetics metabolism, with a mitochondrial impairment and consequent decrease in ATP and reactive oxygen species (ROS) levels. Compound 2 only depolarized the mitochondrial membrane potential, with no interferences in the respiratory chain. Additionally, no macrophages response of nitric oxide (NO) was observed in both compounds. Noteworthy, simple structure modifications in these derivatives induced significant differences in their lethal effects. Thus, this work reinforces the importance of the mechanism of action investigations at the early phases of drug discovery and support further developments of the series.