In vitro chemopreventive and cytotoxic effects of Amazon mosses Leucobryum martianum (Hornsch.) and Leucobryum laevifolium (Broth) extracts.

Several bioactive compounds, such as polyphenols, demonstrate low toxicity and prominent effects on cancer cells with antioxidant, anti-inflammatory, and antitumor activities. Such compounds can be found in Amazon mosses Leucobryum martianum (Hornsch.) Hampe ex Müll. Hal. (Hornsch.) and Leucobryum laevifolium (Broth). Antimutagenic assay with Salmonella enterica serovar Typhimurium and cytotoxicity with different eukaryotic cell lines were carried out to screen aqueous, hydroalcoholic, and ethanolic extracts of those Amazon mosses for anticancer potential. The results indicate the capacity of all extracts of both mosses to exert chemopreventive effects against 4-nitroquinoline-N-oxide (4NQO) and 2-aminoanthracene (2-AA), which are direct or indirect mutagens. In particular, the ethanolic and aqueous extract from L. martianum. The ethanolic extract from L. martianum induces significant cytotoxicity by mitochondrial metabolism and cell membrane disruption pathways to tumor or non-tumor cells. The aqueous extract from L. martianum showed a mainly cytotoxic response in the HepG2 cells, a human liver carcinoma, reaching ~90% cytotoxicity. The same extract did not induce significant damage to normal liver cells (F C3H cells) by membrane interaction pathway. The selective cytotoxicity in the aqueous extract of L. martianum makes it a candidate against liver cancer. Further studies, including in vivo models, are necessary to validate the efficacy and safety of the aqueous extract of L. martianum.

The Cohesive Interactions in Phenylimidazoles.

This work presents a comprehensive study exploring the thermodynamics of the solid phase of a series of phenylimidazoles, encompassing experimental measurements of heat capacity, volatility, and thermal behavior. The influence of successive phenyl group insertions on the imidazole ring on thermodynamic properties and supramolecular behavior was thoroughly examined through the evaluation of 2-phenylimidazole (2-PhI), 4-phenylimidazole (4-PhI), 4,5-diphenylimidazole (4,5-DPhI), and 2,4,5-triphenylimidazole (2,4,5-TPhI). Structural correlations between molecular structure and thermodynamic properties were established. Furthermore, the investigation employed UV-vis spectroscopy and quantum chemical calculations. Additive effects arising from the introduction of phenyl groups were found through the analysis of the solid-liquid and solid-gas equilibria, as well as heat capacities. A good correlation emerged between the thermodynamic properties of sublimation and the molar volume of the unit cell, evident across 2-PhI, 4,5-DPhI, and 2,4,5-TPhI. In contrast to its isomer 2-PhI, 4-PhI exhibited greater cohesive energy due to the stronger N-H···N intermolecular interactions, leading to the disruption of coplanar geometry in the 4-PhI molecules. The observed higher entropies of phase transition (fusion and sublimation) are consistent with the higher structural order observed in the crystalline lattice of 4-PhI.

Antimutagenic and antitumor activities of a water-soluble fraction of soursop (syn Graviola, Annona muricata L.) fruit pulp.

Soursop (Annona muricata) is a tropical tree whose decoction derived from bark, root, seed, or leaf has been used for medicinal uses. In addition, the fruit itself is considered a food, and the juice is utilized to treat heart and liver diseases. The aim of this study was to determine the phenolic content. In addition, a water-soluble fraction of the soursop fruit pulp (WSSP) was examined for the following properties: antioxidant, mutagenic, and antimutagenicity. UV-visible spectrophotometry determined total phenolic content by the Folin-Ciocalteu method to be 11.22 ± 0.6 mg of gallic acid equivalent per gram dried extract, and free-radical scavenging activity by the 2,2'-diphenyl-1-picryl-hydrazyl (DPPH•) showed an EC50 of 1032 µg/ml. In the Salmonella/microsome assay, no marked mutagenicity was induced following WSSP treatment, and a chemopreventive capacity was observed in the antimutagenic assay. The cytotoxicity assays were carried out using the water-soluble tetrazolium salt and lactate dehydrogenase (LDH) assays demonstrated that WSSP induced significant cytotoxicity in MCF-7 and Caco-2 cells, indicating greater effectiveness of cytotoxic action by destroying cell membrane integrity. Data suggest that WSSP may exert beneficial effects as a DNA chemopreventive and antitumor agent.

Marketable 1,3-dimethylamylamine and caffeine-based thermogenic supplements: Regulatory genotoxicity assessment through in vitro and in silico approaches.

The consumption of dietary supplements to enhance physical performance has increased significantly in the last century, especially thermogenic pre-workout supplements. Nevertheless, this industry has faced criticism for inadequate safety measures surveillance in regulatory issues regarding their products. The aims of our study were to investigate two pre-workout supplements with respect to (1) mutagenicity utilizing Salmonella/microsome assay; (2) genotoxicity employing cytokinesis-block micronucleus (CBMN) assay protocols; and (3) hepatocytoxicity using WST cell proliferation, activities of lactate dehydrogenase (LDH) and alkaline phosphatase using human liver carcinoma (HepG2) and mouse fibroblast (F C3H) cells. Oxidative stress was determined through glutathione (GSH) measurement and in silico for predictions of pharmacokinetics and toxicity for the most abundant isolated substances present in these supplements. Both supplements induced mutagenicity in all examined bacterial strains, especially in the presence of exogenous metabolism. Further, tested supplements significantly elevated the formation of micronuclei (MN) as well as other cellular phenomena. Concentration- and time-dependent curves were observed for hepatotoxicity in both studied cell lines. In addition, both supplements decreased levels of intracellular and extracellular GSH. In silico predictions showed that the isolated individual compounds failed to induce the observed outcomes. Our findings provide contributions to the molecular mechanisms underlying two pre-workout supplement-induced toxicity and the need for surveillance.

Bone Density of the Midpalatal Suture After Surgically Assisted Rapid Maxillary Expansion: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the bone density in the midpalatal suture after 10 months of surgically assisted rapid maxillary expansion (SARME) with the separation of the maxilla into 2 segments. METHODS: Sixty multislice computed tomography (MCT) from 20 patients undergoing SARME were analyzed in 3 periods of time (1 MCT per patient on each occasion): (1) 1 week before surgery, (2) postsurgery immediately after completing the expander activation, and (3) 10 months after the expander activation. On all occasions, the bone density was measured in Hounsfield units on MCT scans in axial and coronal sections, in the anterior (A1), middle (A2), and posterior (A3) regions of the midpalatal suture. RESULTS: The mean percentage values of bone density in Hounsfield units, from the 10-month postactivation period to preoperative in the A1, A2, and A3 regions were 68.38%, 38.21%, and 55.90%, respectively, in the axial norm, and 64.06%, 36.81%, and 55.50% in coronal norm (A1 = A3>A2), with no significant difference in the tomographic cuts (P >0.05). There was no correlation between patient age or amount of expansion in the expander and bone density. CONCLUSIONS: The bone density in the midpalatal suture 10 months after SARME is lower than preexpansion. A denser new bone formation along the suture concentrates closer to the extremities rather than in the central region. Although the maturation of the new bone formation in the midpalatal suture is lower 10 months after SARME, it appears to be sufficient for satisfactory clinical results, regardless of patient age or the amount of expansion in the expander.

Boosting life sciences research in Brazil: building a case for a local Drosophila stock center.

Drosophila melanogaster is undoubtedly one of the most useful model organisms in biology. Initially used in solidifying the principles of heredity, and establishing the basic concepts of population genetics and of the synthetic theory of evolution, it can currently offer scientists much more: the possibility of investigating a plethora of cellular and biological mechanisms, from development and function of the immune system to animal neurogenesis, tumorigenesis and beyond. Extensive resources are available for the community of Drosophila researchers worldwide, including an ever-growing number of mutant, transgenic and genomically-edited lines currently carried by stock centers in North America, Europe and Asia. Here, we provide evidence for the importance of stock centers in sustaining the substantial increase in the output of Drosophila research worldwide in recent decades. We also discuss the challenges that Brazilian Drosophila scientists face to keep their research projects internationally competitive, and argue that difficulties in importing fly lines from international stock centers have significantly stalled the progression of all Drosophila research areas in the country. Establishing a local stock center might be the first step towards building a strong local Drosophila community that will likely contribute to all areas of life sciences research.

Outcomes of the "Calcaneo-stop" procedure for treating symptomatic flexible flatfoot in children: A systematic review and meta-analysis of 2394 feet.

BACKGROUND: This study evaluates the efficacy of the calcaneo-stop (C-Stop) procedure's effectiveness in treating symptomatic flexible flatfoot (FFF) in children. METHODS: A systematic review and meta-analysis were conducted using PubMed, Embase, and Cochrane databases to identify studies until 2023 on the outcomes of the C-Stop procedure in children with FFF. The risk of bias was assessed using MINORS criteria. RESULTS: Of 85 studies screened, 20 involving 2394 feet from 1415 patients (mean age 11.2 ± 1.3 years) were included. Post-procedure, significant improvements were noted in pain reduction (93.5%), heel alignment (95.21%), and radiological measures, including reductions in Kite (7.32º), Meary (11.65º), Costa-Bartani angles (17.11º), talar declination (12.63º) and increase in Calcaneal Pitch Angle (5.92º). AOFAS scores increased by 22.32 points on average, with 94.83% reporting high satisfaction. Complication rate was low (7.8%). CONCLUSIONS: The C-Stop procedure is effective for treating FFF in children, offering significant clinical, radiological, and functional improvements with high patient satisfaction and a low complication rate. LEVEL OF EVIDENCE: Level IV, Systematic review of Level-IV studies.

The First Brazilian Cardiovascular Registry of Atrial Fibrillation: Primary Results of the RECALL Study.

BACKGROUND: It is estimated that atrial fibrillation (AF) affects approximately 1.5 million people in Brazil; however, epidemiological data are limited. We sought to evaluate the characteristics, treatment patterns, and clinical outcomes in patients with AF in Brazil by creating the first nationwide prospective registry. METHODS: RECALL was a multicenter, prospective registry that included and followed for 1 year 4,585 patients with AF at 89 sites across Brazil from April 2012 to August 2019. Patient characteristics, concomitant medication use, and clinical outcomes were analyzed using descriptive statistics and multivariable models. RESULTS: Of 4,585 patients enrolled, the median age was 70 (61, 78) years, 46% were women, and 53.8% had permanent AF. Only 4.4% of patients had a history of previous AF ablation and 25.2% had a previous cardioversion. The mean (SD) CHA2DS2-VASc score was 3.2 (1.6); median HAS-BLED score was 2 (2, 3). At baseline, 22% were not on anticoagulants. Of those taking anticoagulants, 62.6% were taking vitamin K antagonists and 37.4% were taking direct oral anticoagulants. The primary reasons for not using an oral anticoagulant were physician judgment (24.6%) and difficulty in controlling (14.7%) or performing (9.9%) INR. Mean (SD) TTR for the study period was 49.5% (27.5). During follow-up, the use of anticoagulants and INR in the therapeutic range increased to 87.1% and 59.1%, respectively. The rates/100 patient-years of death, hospitalization due to AF, AF ablation, cardioversion, stroke, systemic embolism, and major bleeding were 5.76 (5.12-6.47), 15.8 (14.6-17.0), 5.0 (4.4-5.7), 1.8 (1.4-2.2), 2.77 (2.32-3.32), 1.01 (0.75-1.36), and 2.21 (1.81-2.70). Older age, permanent AF, New York Heart Association class III/IV, chronic kidney disease, peripheral arterial disease, stroke, chronic obstructive pulmonary disease, and dementia were independently associated with increased mortality while the use of anticoagulant was associated with lower risk of death. CONCLUSIONS: RECALL represents the largest prospective registry of patients with AF in Latin America. Our findings highlight important gaps in treatment, which can inform clinical practice and guide future interventions to improve the care of these patients.

How great is the stabilization of crowded polyphenylbiphenyls by London dispersion?

Decaphenylbiphenyl (1) and 2,2',4,4',6,6'-hexaphenylbiphenyl (2) are bulky molecules expected to be greatly destabilized by steric crowding. Herein, through a combined experimental and computational approach, we evaluate the molecular energetics of crowded biphenyls. This is complemented by the study of phase equilibria for 1 and 2. Compound 1 shows a rich phase behavior, displaying an unusual interconversion between two polymorphs. Surprisingly, the polymorph with distorted molecules of C1 symmetry is found to have the highest melting point and to be the one that is preferentially formed. The thermodynamic results also indicate that the polymorph displaying the more regular D2 molecular geometry has larger heat capacity and is probably the more stable at lower temperatures. The melting and sublimation data clearly reveal the weakening of cohesive forces in crowded biphenyls due to the lower molecular surface area. The experimental quantification of the intramolecular interactions in 1 and 2 indicated, using homodesmotic reactions, a molecular stabilization of about 30 kJ mol-1. We attribute the origin of this stabilization in both compounds to the existence of two parallel-displaced π⋯π interactions between the ortho-phenyl substituents on each side of the central biphenyl. Computational calculations with dispersion-corrected DFT methods underestimate the stabilization in 1, unless the steric crowding is well balanced in a homodesmotic scheme. This work demonstrates that London dispersion forces are important in crowded aromatic systems, making these molecules considerably more stable than previously thought.

Cross-cultural adaptation of the Skin Cancer Index into Brazilian Portuguese for patients with cervicofacial nonmelanoma skin cancer.

PURPOSE: This study aimed to translate the Skin Cancer Index (SCI) into Portuguese, adapt it for Brazilian culture, and clinically validate it. METHODS: A five-stage cross-cultural adaptation model was followed, with subsequent clinical validation. Inter-rater agreement was assessed using the content validity index (CVI). The hypothesis of the non-inferiority of the CVI at 80% probability level was evaluated using an exact binomial test. We used Spearman's rank-order and Pearson's product-moment correlation analysis, internal consistency using McDonald's ω and Cronbach's α metric, and construct validity using confirmatory factor analysis. The factorial model was validated using the chi-squared test, root mean square error of approximation (RMSEA), comparative fit index (CFI), and standardized root mean square residual (SRMR). RESULTS: The first stage yielded two independent translations. After synthesis, back-translation, and review, the prefinal version was tested on 40 patients. Inter-rater agreement indices on content validity were significantly higher than 80% (p < 0.05). The SCI remained stable, and the Spearman's rank-order (rs), Pearson product-moment (r), and intraclass correlation coefficients were > 0.9, indicating excellent reliability. The reliability of McDonald's ω was considered ideal (> 0.8) in all subdimensions and scale. Cronbach's α was considered ideal in the "Emotional" and "Social" subdimensions and scale. Construct validity was observed in all subdimensions and scale through the criteria (χ2) p value > 0.05, RMSEA < 0.08, CFI ≥ 0.9, and SRMR ≤ 0.08. CONCLUSION: The cross-cultural adaptation of the SCI to Portuguese for Brazilian culture showed content validity and reliability, contributing to quality of life assessment in patients with NMSC.

Effectiveness of intravesical ozone in interstitial cystitis by the O'Leary-Sant symptom index.

INTRODUCTION AND HYPOTHESIS: A prospective clinical, preliminary study was performed in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) who were nonresponders to conventional treatment and received intravesical ozone as a therapeutic alternative. METHODS: Sixteen patients received six applications of intravesical ozone at a concentration of 41 µg/mL. We evaluated therapeutic efficacy by the percentage reduction of Interstitial Cystitis Symptom and Problem Index scores (ICSI/ICPI-the O'Leary-Sant symptom index), recurrence rate, nonresponse, and side effects in scores collected on admission (pre-treatment), at the end of the therapeutic protocol (post-treatment), and 180 days (follow-up) after the last ozone application. RESULTS: The mean age of women was 52.9 years (SD: 15.5), and the duration of symptoms was 5.7 years (SD: 7.1). The median ICSI on admission was 17 (IQR: 14.25-19.5) and at follow-up was 0.5 (IQR: 0-2), with a reduction of 97.5% (CI: 85.7-100). The median ICSI/ICPI on admission was 31.5 (IQR: 29-35.2) and at follow-up was 2.0 (IQR: 0-3.75), with a reduction of 92.3% (CI: 88.8-100). The recurrence rate was only 6.25%, and no patients were nonresponders to the treatment. CONCLUSIONS: The application of intravesical ozone was effective in the treatment of patients with IC/BPS who were nonresponders to conventional therapy, showing a progressive and safe effect, at least in the short term.

Anti-Trypanosoma cruzi Activity, Mutagenicity, Hepatocytotoxicity and Nitroreductase Enzyme Evaluation of 3-Nitrotriazole, 2-Nitroimidazole and Triazole Derivatives.

Chagas disease (CD), which is caused by Trypanosoma cruzi and was discovered more than 100 years ago, remains the leading cause of death from parasitic diseases in the Americas. As a curative treatment is only available for the acute phase of CD, the search for new therapeutic options is urgent. In this study, nitroazole and azole compounds were synthesized and underwent molecular modeling, anti-T. cruzi evaluations and nitroreductase enzymatic assays. The compounds were designed as possible inhibitors of ergosterol biosynthesis and/or as substrates of nitroreductase enzymes. The in vitro evaluation against T. cruzi clearly showed that nitrotriazole compounds are significantly more potent than nitroimidazoles and triazoles. When their carbonyls were reduced to hydroxyl groups, the compounds showed a significant increase in activity. In addition, these substances showed potential for action via nitroreductase activation, as the substances were metabolized at higher rates than benznidazole (BZN), a reference drug against CD. Among the compounds, 1-(2,4-difluorophenyl)-2-(3-nitro-1H-1,2,4-triazol-1-yl)ethanol (8) is the most potent and selective of the series, with an IC50 of 0.39 µM and selectivity index of 3077; compared to BZN, 8 is 4-fold more potent and 2-fold more selective. Moreover, this compound was not mutagenic at any of the concentrations evaluated, exhibited a favorable in silico ADMET profile and showed a low potential for hepatotoxicity, as evidenced by the high values of CC50 in HepG2 cells. Furthermore, compared to BZN, derivative 8 showed a higher rate of conversion by nitroreductase and was metabolized three times more quickly when both compounds were tested at a concentration of 50 µM. The results obtained by the enzymatic evaluation and molecular docking studies suggest that, as planned, nitroazole derivatives may utilize the nitroreductase metabolism pathway as their main mechanism of action against Trypanosoma cruzi. In summary, we have successfully identified and characterized new nitrotriazole analogs, demonstrating their potential as promising candidates for the development of Chagas disease drug candidates that function via nitroreductase activation, are considerably selective and show no mutagenic potential.

Characterization of sporadic somatotropinomas with high GIP receptor expression.

PURPOSE: To analyze the expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in somatotropinomas specimens and compare clinical, biochemical, radiological, therapeutic, molecular, and pathological data among those who overexpressed (GIPR +) and those who did not overexpress (GIPR - ) GIPR. METHODS: Clinical, biochemical, radiological, molecular, and pathological data were collected. GNAS1 sequencing was performed with the Sanger method. Protein expression of somatostatin receptor subtypes 2 and 5 and CAM 5.2 were analyzed by immunohistochemistry. Quantitative real-time PCR was performed to analyze the mRNA expression of GIPR with the TaqMan® method. Positive expression was considered when the fold change (FC) was above 17.2 (GIPR +). RESULTS: A total of 74 patients (54% female) were included. Eighteen tumors (24%) were GIPR + . Gsp mutation was detected in 30 tumors (40%). GIPR + tumors were more frequently densely granulated adenomas (83% vs 47%, p = 0.028). There was no difference in clinical, biochemical, radiological, therapeutic (surgical cure or response to medical therapy), or other pathological features between GIPR + and GIPR -  tumors. Twenty-eight out of 56 (50%) GIPR -  tumors harbored a gsp mutation, whereas two out of 18 (11%) GIPR + tumors harbored a gsp mutation (p = 0.005). CONCLUSION: We described, for the first time, that GIPR + and gsp mutations are not mutually exclusive, but gsp mutations are less common in GIPR + tumors. GIPR + and GIPR -  tumors have similar clinical, biochemical, radiological, therapeutic, and pathological features, with the exception of a high frequency of densely granulated adenomas among GIPR + tumors.

Fracture Risk After Bariatric Surgery: A Systematic Literature Review and Meta-Analysis.

OBJECTIVE: Bariatric surgery has undeniable benefits for cardiovascular and metabolic health, but it can result in negative effects on mineral and bone metabolism. This study aimed to review the current data on fractures after the main types of bariatric surgery. METHODS: Therefore, a systematic review was performed using the electronic literature available in the databases LILACS, CENTRAL, Web of Science, Embase, and PubMed/MEDLINE, with results until January 2021. Keywords were descriptors for bariatric surgery or bariatric medicine or bariatrics or gastroplasty and bone or bones or bone fractures, referenced in all words of the text in the study. RESULTS: The meta-analysis of observational studies and interventional trials showed that the risk of any type of fracture was higher in the surgical group than in the nonsurgical group (relative risk [RR], 1.20 [95% confidence interval {CI}, 1.15-1.26; P < .00001; Phetero < 0.000001; I2 = 94%], and RR, 1.16 [95% CI, 1.00-1.33; P = .04; Phetero = 0.27; I2 = 23%], respectively). It is worth noting that the included interventional studies have a low rating on the risk of bias assessment scales. Compared with those who underwent restrictive procedures, subjects had an increased fracture risk after malabsorptive procedures (RR, 0.49 [95% CI, 0.40-0.61; P < .00001); Phetero = 0.96; I2 = 0%). CONCLUSION: We found that bariatric procedures are associated with an increased risk of fractures, especially the malabsorptive techniques.

IPA and WPA-SOAP position statement on deprivation of liberty of older persons with mental health conditions.

In recognition of the challenges faced by older persons deprived of their liberty, a call was made for input into the 2022 report to the United Nations Human Rights Council (HRC) on older persons. This Position Statement outlines the views of two global organizations, the International Psychogeriatric Association (IPA) and the World Psychiatric Association Section of Old Age Psychiatry (WPA-SOAP), working together to provide rights and dignity-based mental health services to older persons and it was sent to the Independent Expert on the enjoyment of all human rights by older persons at HRC.

Analysis of pain relief and functional recovery in patients with rotator cuff tendinopathy through therapeutic ultrasound and photobiomodulation therapy: a comparative study.

This study aimed to compare shoulder tendinopathy treatment with therapeutic ultrasound combined with LED photobiomodulation therapy using LED-infrared (850 nm) or LED-red (640 nm). The study assessed 75 patients, aged 45 to 70 years, distributed into five experimental groups (15 patients each): therapeutic ultrasound (US), infrared light irradiation (IR), visible red light irradiation (VR), infrared light and ultrasound combined (IR-US), and red light in conjunction with ultrasound (VR-US). The ultrasound parameters are 1 MHz, 0.5 W/cm2 (SATA), and 100 Hz repetition rate, applied for 4 min each session. LED irradiation protocols were as follows: 3 points, 7.5 J per point, IR-LED 750 mW, 10 s, VR-LED 250 mW, 30 s. LED irradiation is followed by ultrasound in the combined therapies. The efficiency of the five therapies was evaluated assessing 12 parameters: quality of life (Health Assessment Questionnaire, HAQ), pain intensity (Visual Analog Scale, VAS), articular amplitude of shoulder movement (flexion, extension, abduction, adduction, medial rotation, lateral rotation), muscle strength (abduction, lateral rotation), and electromyography (lateral rotation, abduction). Treatments comprised 12 sessions for 4 weeks. Intra-group analysis showed that the five therapies significantly improved the recovery of all parameters after treatment. Regarding the comparison of irradiated therapies and ultrasound, statistical analysis showed that IR-US was a better treatment than US for all 12 parameters. IR treatment exceeded US on 9 items, whereas that VR and VR-US therapies exceeded US in 7 and 10 parameters, respectively (p < 0.05). Because of that, IR-US shows to be the best treatment for rotator cuff tendinopathy. In conclusion, improvements in quality of life, pain intensity relief, shoulder amplitude motion, and muscle strength force obtained with ultrasound therapy are enhanced by adding infrared LED irradiation to ultrasound for patients suffering from rotator cuff tendinopathy. This study was registered with the Brazilian Registry of Clinical Trials (ReBEC) under Universal Trial Number (UTN) U1111-1219-3594 (2018/22/08).

Toxicity of the essential oil from Tetradenia riparia (Hochstetter.) Codd (Lamiaceae) and its principal constituent against malaria and dengue vectors and non-target animals.

Malaria and dengue are diseases transmitted by mosquitoes of the genera Anopheles and Aedes resistant to commercial insecticides, which are toxic to non-target animals. Alternatively, eco-friendly strategies have focused on searching for essential oil (EO) from plants to control these mosquitoes. In this aspect, this study was carried out to investigate the toxicity of the EO from Tetradenia riparia and its main constituent against Anopheles and Aedes larvae and non-target animals Toxorhynchites haemorrhoidalis and Gambusia affinis. The mechanism of the larvicidal action of the EO and its main compound was investigated by the acetylcholinesterase (AChE) inhibition. The EO from T. riparia was extracted by hydrodistillation with yield of 1.4 ± 0.17%. The analysis of the EO by GC-MS and GC-FID revealed fenchone (38.62%) as the main compound. The EO (100 ppm) showed larvicidal activity against Anopheles and Aedes larvae (91 to 100% of mortality) (LC50 from 29.31 to 40.76 ppm). On the other hand, fenchone (10 ppm) showed more activity (89 to 100% of mortality) (LC50 from 5.93 to 7.00 ppm) than the EO. The EO and fenchone caused the inhibition of AChE (IC50 from 1.93 to 2.65 ppm), suggesting the inhibition of this enzyme as a possible mechanism of larvicidal action. Regarding toxicity, the EO (1000 ppm) and fenchone (100 ppm) showed low toxicity against T. haemorrhoidalis and G. affinis (9 to 74% of mortality) (LC50 from 170.50 to 924.89 ppm) (SI/PSF from 17.99 to 31.91) than the α-cypermethrin (0.52 ppm) which was extremally toxic against these non-target animals (100% of mortality, LC50 from 0.22 to 0.29 ppm). This significant larvicidal activity of the T. riparia EO and its main constituent, along with the low toxicity towards non-target organisms indicate these samples as a possible eco-friendly alternative for the control of malaria and dengue vectors.

[The HEARTS Initiative in Cuba: experience of five years of implementationA Iniciativa HEARTS em Cuba: experiências após 5 anos de implementação]. / La Iniciativa HEARTS en Cuba: experiencias tras 5 años de implementación.

In order to describe the changes in the control of arterial hypertension from 2016 to 2021 and the relationship between the progress made and the maturity of implementation of the HEARTS Initiative at the first level of care in Cuba, a prospective implementation study was designed to promote the correct measurement of blood pressure with validated automatic sphygmomanometers, risk-based care, introduction of standardized antihypertensive treatment protocols, secondary prevention, and teamwork. Patient education, active case-finding, and community activities were also encouraged. Data were obtained from implementation logs and were analyzed with SPSS Statistics V21; outcome values and 95% confidence intervals were reported. Population indicators were evaluated: registration coverage, control between treatments, population control, and the HEARTS in the Americas Maturity Index. The number of participating centers increased from a single demonstration center in 2016 to 22 polyclinics in six provinces and seven municipalities in 2021. There was a significant increase in the absolute values for the total population served, number of hypertensive patients registered, controlled patients among those treated, and controlled hypertensive patients among all adults, although with annual variations in percentages of coverage, control between treatments, and population control. The greatest progress occurred in centers with high-performance health teams. Five years after implementation of the HEARTS Initiative in Cuba, the methodology is becoming institutionalized.

A fim de descrever as mudanças no controle da hipertensão arterial de 2016 a 2021 e a relação entre o progresso e a maturidade da implementação da Iniciativa HEARTS no primeiro nível de atenção em Cuba, foi elaborado um estudo prospectivo de implementação que promoveu a aferição correta da pressão arterial com esfigmomanômetros automáticos validados, cuidados baseados em risco, a introdução de protocolos padronizados de tratamento anti-hipertensivo, a prevenção secundária e o trabalho em equipe. A educação dos pacientes, a busca ativa de casos e as atividades comunitárias também foram incentivadas. Os dados foram obtidos a partir dos registros de implementação e foram analisados com o programa de estatística SPSS versão 21. São relatadas medidas de desfecho e seus intervalos de confiança de 95%. Foram avaliados os seguintes indicadores populacionais: cobertura de registro, controle entre os pacientes tratados e controle populacional, bem como o índice de maturidade dos processos da Iniciativa HEARTS nas Américas. Comparativamente, entre 2016 e 2021, o número de centros participantes aumentou de um só centro de demonstração para 22 policlínicas em 6 províncias e 7 municípios. Evidenciou-se um aumento significativo nos valores absolutos da população total atendida, do número de pessoas com hipertensão cadastradas, de pacientes controlados entre os tratados e de pessoas com hipertensão controlada entre todos os adultos, embora com variações anuais nos percentuais de cobertura, no controle entre os tratados e no controle populacional. Os maiores avanços ocorreram nos centros que têm equipes de saúde de alto desempenho. Cinco anos após a implementação da Iniciativa HEARTS em Cuba, avança-se rumo à institucionalização da metodologia.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Structural Insights into the Molecular Recognition Mechanism of the Cancer and Pathogenic Epitope, LacdiNAc by Immune-Related Lectins.

Interactions of glycan-specific epitopes to human lectin receptors represent novel immune checkpoints for investigating cancer and infection diseases. By employing a multidisciplinary approach that combines isothermal titration calorimetry, NMR spectroscopy, molecular dynamics simulations, and X-ray crystallography, we investigated the molecular determinants that govern the recognition of the tumour and pathogenic glycobiomarker LacdiNAc (GalNAcß1-4GlcNAc, LDN), including their comparison with the ubiquitous LacNAc epitope (Galß1-4GlcNAc, LN), by two human immune-related lectins, galectin-3 (hGal-3) and the macrophage galactose C-type lectin (hMGL). A different mechanism of binding and interactions was observed for the hGal-3/LDN and hMGL/LDN complexes, which explains the remarkable difference in the binding specificity of LDN and LN by these two lectins. The new structural clues reported herein are fundamental for the chemical design of mimetics targeting hGal-3/hMGL recognition process.