Investigating the anti-growth, anti-resistance, and anti-virulence activities of Schoepfia schreberi J.F.Gmel. against the superbug Acinetobacter baumannii.

Schoepfia schreberi has been used in Mayan folk medicine to treat diarrhea and cough. This study aimed to determine the anti-growth, anti-resistance, and/or anti-virulence activities of S. schreberi extracts against Acinetobacter baumannii, a pathogen leader that causes healthcare-associated infections with high rates of drug-resistant including carbapenems, the last line of antibiotics known as superbugs, and analyze their composition using HPLC-DAD. Ethyl acetate (SSB-3) and methanol (SSB-4) bark extracts exhibit antimicrobial and biocidal effects against drug-susceptible and drug-resistant A. baumannii. Chemical analysis revealed that SSB-3 and SSB-4 contained of gallic and ellagic acids derivatives. The anti-resistance activity of the extracts revealed that SSB-3 or SSB-4, combined with imipenem, exhibited potent antibiotic reversal activity against A. baumannii by acting as pump efflux modulators. The extracts also displayed activity against surface motility of A. baumannii and its capacity to survive reactive oxygen species. This study suggests that S. schreberi can be considered a source of antibiotics, even adjuvanted compounds, as anti-resistant or anti-virulence agents against A. baumannii, contributing to ethnopharmacological knowledge and reappraisal of Mayan medicinal flora, and supporting the traditional use of the bark of the medicinal plant S. schreberi for the treatment of infectious diseases.

Nickel(II)-Catalyzed Formal [3+2] Cycloadditions between Indoles and Donor-Acceptor Cyclopropanes.

This article describes the development of a nickel-catalyzed regio- and diastereoselective formal [3+2] cycloaddition between N-substituted indoles and donor-acceptor cyclopropanes to synthesize cyclopenta[b]indoles. Optimized reaction conditions provide the desired nitrogen-containing cycloadducts in up to 93% yield and dr 8.6:1 with complete regioselectivity. The substrate scope showed high tolerance to various substituted indoles and cyclopropanes, resulting in the synthesis of six new cyclopenta[b]indoles and the isolation of five derivatives previously reported in the literature. In addition, a mechanistic proposal for the reaction was studied through online reaction monitoring by ESI-MS, allowing for the identification of the reactive intermediates in the Ni(II) catalyzed process. X-ray crystallography confirmed the structure and relative endo stereochemistry of the products. This method enables the fast and efficient construction of fused indolines from readily accessible starting materials.

Genomic epidemiology of the primary methicillin-resistant Staphylococcus aureus clones causing invasive infections in Paraguayan children.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major human pathogens. It could carry numerous resistance genes and virulence factors in its genome, some of which are related to the severity of the infection. An observational, descriptive, cross-sectional study was designed to molecularly analyze MRSA isolates that cause invasive infections in Paraguayan children from 2009 to 2013. Ten representative MRSA isolates of the main clonal complex identified were analyzed with short-read paired-end sequencing and assessed for the virulome, resistome, and phylogenetic relationships. All the genetically linked MRSA isolates were recovered from diverse clinical sources, patients, and hospitals at broad gap periods. The pan-genomic analysis of these clones revealed three major and different clonal complexes (CC30, CC5, and CC8), each composed of clones closely related to each other. The CC30 genomes prove to be a successful clone, strongly installed and disseminated throughout our country, and closely related to other CC30 public genomes from the region and the world. The CC5 shows the highest genetic variability, and the CC8 carried the complete arginine catabolic mobile element (ACME), closely related to the USA300-NAE-ACME+, identified as the major cause of CA-MRSA infections in North America. Multiple virulence and resistance genes were identified for the first time in this study, highlighting the complex virulence profiles of MRSA circulating in the country. This study opens a wide range of new possibilities for future projects and trials to improve the existing knowledge on the epidemiology of MRSA circulating in Paraguay. IMPORTANCE: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide. The most frequent MRSA clones identified in Paraguay in previous studies (including community and hospital acquired) were the Pediatric (CC5-ST5-IV), the Cordobes-Chilean (CC5-ST5-I), the SouthWest Pacific (CC30-ST30-IV), and the Brazilian (CC8-ST239-III) clones. In this study, the pan-genomic analysis of the most representative MRSA clones circulating in invasive infection in Paraguayan children over the years 2009-2013, such as the CC30-ST30-IV, CC5-ST5-IV, and CC8-ST8-IV, was carried out to evaluate their genetic diversity, their repertoire of virulence factors, and antimicrobial resistance determinants. This revealed multiple virulence and resistance genes, highlighting the complex virulence profiles of MRSA circulating in Paraguay. Our work is the first genomic study of MRSA in Paraguay and will contribute to the development of genomic surveillance in the region and our understanding of the global epidemiology of this pathogen.

Results of the transition from posterolateral to anterior minimally invasive approach for total hip arthroplasty.

BACKGROUND: The anterior minimally invasive (AMI) approach reduces soft tissue damage, risk of dislocation and enhances recovery, but it is associated with certain complications. The aim of this study is to compare the outcomes of patients who underwent total hip arthroplasty (THA) through posterolateral (PL) and AMI approaches performed by the same surgeon, in order to determine the learning curve associated with this new approach. METHODS: This retrospective cohort study included patients who underwent THA via PL and AMI approach between 2017 and 2022, with a minimum follow-up of 1 year. Hip fracture and oncologic patients were excluded. Demographic variables, functional scores and perioperative complications were assessed. A bivariate analysis was performed to identify differences between groups. RESULTS: Data of 124 AMI and 120 PL patients were analyzed. Demographic characteristics among groups were homogeneous. Functional outcomes at 3 months were superior for AMI (Oxford: 43 vs. 38; p < 0.05), no dislocations were identified (0% vs. 4.2%; p < 0.05) and no differences in the transfusion rate were found (6.5% AMI vs. 6.7% PL; p = 0.996). Infection rate was 4% for AMI and 3.4% for PL (p = 0.572). Surgical time was shorter for the PL approach, but the median surgical time of the last 25 AMI cases was shorter. CONCLUSIONS: The AMI approach is an excellent alternative for patients requiring THA. Although surgical time and perioperative bleeding were greater during the learning curve, this approach offers improved functional outcomes and a lower dislocation rate, without significant differences in transfusion and infection outcomes, demonstrating that responsible innovation and safe implementation of new techniques is possible.

Compartment syndrome of the foot: A case report.

Background: Exercise-induced compartment syndrome is a condition characterized by elevated pressure within a muscle compartment, resulting from repetitive loading or participation in sports activities. Primarily affecting the medial compartment of the foot, this rare condition manifests as sudden-onset pain in the medial aspect of the foot, without a discernible history of trauma, occurring during or after physical exertion. Diagnosis is primarily clinical in nature, as diagnostic imaging techniques provide limited utility. Conclusions: Exercise-induced compartment syndrome is a rare syndrome with prolonged implications such as contractures, claw toes, muscle weakness, and sensory neuropathy. Hence, it is imperative for orthopedic surgeons to be familiar with this condition in order to facilitate timely diagnosis and treatment.

Functionalizing Dendrimers for Targeted Delivery of Bioactive Molecules to Macrophages: A Potential Treatment for Mycobacterium tuberculosis Infection-A Review.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that replicates inside human alveolar macrophages. This disease causes significant morbidity and mortality throughout the world. According to the World Health Organization 1.4 million people died of this disease in 2021. This indicates that despite the progress of modern medicine, improvements in diagnostics, and the development of drug susceptibility tests, TB remains a global threat to public health. In this sense, host-directed therapy may provide a new approach to the cure of TB, and the expression of miRNAs has been correlated with a change in the concentration of various inflammatory mediators whose concentrations are responsible for the pathophysiology of M. tuberculosis infection. Thus, the administration of miRNAs may help to modulate the immune response of organisms. However, direct administration of miRNAs, without adequate encapsulation, exposes nucleic acids to the activity of cytosolic nucleases, limiting their application. Dendrimers are a family of highly branched molecules with a well-defined architecture and a branched conformation which gives rise to cavities that facilitate physical immobilization, and functional groups that allow chemical interaction with molecules of interest. Additionally, dendrimers can be easily functionalized to target different cells, macrophages among them. In this sense, various studies have proposed the use of different cell receptors as target molecules to aim dendrimers at macrophages and thus release drugs or nucleic acids in the cell of interest. Based on the considerations, the primary objective of this review is to comprehensively explore the potential of functionalized dendrimers as delivery vectors for miRNAs and other therapeutic agents into macrophages. This work aims to provide insights into the use of functionalized dendrimers as an innovative approach for TB treatment, focusing on their ability to target and deliver therapeutic cargo to macrophages.

Bilateral asymmetric traumatic hip dislocation associated with epiphysiolysis of the femoral head in an adolescent patient.

Background: Bilateral asymmetric hip dislocation is uncommon in childhood, even more when associated with epiphyseal slippage, leading to catastrophic complications of the affected joints, requiring additional surgical interventions, and increasing patient morbidity. In this article, we present the case of a 15 years-old patient with a post-traumatic bilateral hip dislocation with epiphyseal slippage, initially managed with open reduction and fixation, with subsequent need of total hip arthroplasty. Afterward, the patient presented satisfactory outcomes. Conclusion: Hip dislocation associated with transphyseal fracture is an injury that leads to joint destruction, and despite timely management, the prognosis is poor; however, efforts should be made to provide opportune care to obtain the best outcome.

Impacto del SARS-CoV2 en el control de pacientes diabéticos del CESFAM Las Américas, Talca / Impact of SARS-CoV2 on the control of diabetic patients CESFAM Las Américas, Talca

INTRODUCTION: Type 2 diabetes mellitus is a metabolic disorder that affects all aspects of the life and family of the person who suffers from it. The SARS-COV-2 infection pandemic has generated an immense problem at the health system level, causing a significant overload and a complexity of the services to attend to the infection. The foregoing has led many people to lose their chronic controls and cannot take care of themselves properly. OBJECTIVES: To measure the impact of the SARS-COV2 pandemic on the control of diabetic patients at CESFAM Las Américas, Talca city. METHODS: Observational, descriptive/analytical study of the Cardiovascular Health Program at CESFAM Las Américas in the city of Talca, of type 2 diabetic patients, enrolled under control, evaluated between December 2019 and September 2021. Information cutoffs will be 12 months and 15 months RESULTS: In a comparative analysis, we found significant differences with an increase in the indicators BMI, Glycemia, HAb1c and Triglycerides during the time of the Pandemic. However, clinically modest.

Exploring the Chemistry of Ocimum Species under Specific Extractions and Chromatographic Methods: A Systematic Review.

Ocimum is considered the largest genus in the Lamiacea family. The genus includes basil, a group of aromatic plants with a wide range of culinary uses that nowadays draws attention for its medicinal and pharmaceutical potential. This systematic review intends to explore the chemical composition of nonessential oils and their variation across different Ocimum species. Moreover, we aimed to identify the state of knowledge regarding the molecular space in this genus as well as the different methods of extraction/identification and geographical location. Seventy-nine eligible articles were selected for the final analysis, from which we extracted more than 300 molecules. We found that the countries with the highest number of studies into Ocimum species are India, Nigeria, Brazil, and Egypt. However, from all known species of Ocimum, only 12 were found to have an extensive chemical characterization, particularly Ocimum basilicum and Ocimum tenuiflorum. Our study focused especially on alcoholic, hydroalcoholic, and water extracts, in which the main techniques for compound identifications are GC-MS, LC-MS, and LC-UV. Across the compiled molecules, we found a wide variety of compounds, especially flavonoids, phenolic acids, and terpenoids, suggesting that this genus could be a very useful source of possible bioactive compounds. The information collected in this review also emphasizes the huge gap between the vast number of Ocimum species discovered and the number of studies in each of them that determined the chemical characterization.

In silico approaches to develop new phenyl-pyrimidines as glycogen synthase kinase 3 (GSK-3) inhibitors with halogen-bonding capabilities: 3D-QSAR CoMFA/CoMSIA, molecular docking and molecular dynamics studies.

Glycogen synthase kinase 3 (GSK-3) is involved in different diseases, such as manic-depressive illness, Alzheimer's disease and cancer. Studies have shown that insulin inhibits GSK-3 to keep glycogen synthase active. Inhibiting GSK-3 may have an indirect pro-insulin effect by favouring glycogen synthesis. Therefore, the development of GSK-3 inhibitors can be a useful alternative for the treatment of type II diabetes. Aminopyrimidine derivatives already proved to be interesting GSK-3 inhibitors. In the current study, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) have been performed on a series of 122 aminopyrimidine derivatives in order to generate a robust model for the rational design of new compounds with promising antidiabetic activity. The q2 values obtained for the best CoMFA and CoMSIA models have been 0.563 and 0.598, respectively. In addition, the r2 values have been 0.823 and 0.925 for CoMFA and CoMSIA, respectively. The models were statistically validated, and from the contour maps analysis, a proposal of 10 new compounds has been generated, with predicted pIC50 higher than 9. The final contribution of our work is that: (a) we provide an extensive structure-activity relationship for GSK-3 inhibitory pyrimidines; and (b) these models may speed up the discovery of GSK-3 inhibitors based on the aminopyrimidine scaffold. Finally, we carried out docking and molecular dynamics studies of the two best candidates, which were shown to establish halogen-bond interactions with the enzyme.Communicated by Ramaswamy H. Sarma.

Cirugía laparoscópica en pacientes con obesidad mórbida y cáncer de endometrio

Introducción: La cirugía, en pacientes con obesidad mórbida, como tratamiento del cáncer ginecológico supone un reto para el cirujano y el anestesiólogo, pues se asocia a un incremento de las complicaciones intra y posoperatorias. Objetivo: Describir los principales resultados con la cirugía laparoscópica, en pacientes con obesidad mórbida y adenocarcinoma de endometrio, tratadas en el Instituto Nacional de Oncología y Radiobiología (INOR) de la Habana, Cuba, en el período comprendido enero de 2019 a marzo de 2020. Método: Se realizó un estudio descriptivo, observacional y transversal, en 22 pacientes con índice de masa corporal mayor de 40 kg/m2 y diagnóstico de adenocarcinoma de endometrio, que fueron sometidas a cirugía laparoscópica. El dato primario fue obtenido a través de las historias clínicas, con los que se confeccionó una base de datos en una hoja de Microsoft Excel para sintetizar toda la información. Resultados: Predominó la edad entre 61 a 70 años. El adenocarcinoma endometrioide fue el más frecuente con el 77,27 %. El grado de diferenciación fue el bien diferenciado, infiltrando menos del 50 % del miometrio. El estadiamiento quirúrgico predominante fue el IA (72,72 %). El sangrado transoperatorio fue de 78,9 ± 5,7ml (rango 10 y 200 ml), la media del acto operatorio de 82 min (rango 75-132 min), y la estadía hospitalaria de menos de 24 horas (90,90 %). La conversión quirúrgica se realizó en el 4,54 % de los casos. Conclusiones: Las pacientes con obesidad mórbida pueden beneficiarse del abordaje laparoscópico para el tratamiento y la estatificación quirúrgica laparoscópica del carcinoma endometrial, lo que disminuye la morbilidad y la estadía hospitalaria.

Introduction: Surgery in morbidly obese patients as a treatment for gynecologic cancer is a challenge for surgeons and anesthesiologists, since it is associated with the processes of increasing intraoperative and postoperative complications. Objective: To describe the main results gained with the use of laparoscopic surgery in patients with morbid obesity and endometrial adenocarcinoma treated at the Instituto Nacional de Oncología y Radiobiología (INOR) of Havana, Cuba, from January 2019 to March 2020. Method: A descriptive, observational, cross-sectional study was carried out in 22 patients, with body mass index more than 40 kg/m2 and diagnosis of endometrial adenocarcinoma, who underwent laparoscopic surgery. The primary data was obtained from the medical records, which were used to create a database in a Microsoft Excel spreadsheet to synthesize all the information. Results: The predominant age group was between 61 and 70 years old. Endometrial adenocarcinoma was the most frequent cancer (77.27%). The degree of differentiation was well differentiated, infiltrating less than 50 % of the myometrium. The predominant surgical staging was IA (72.72%). Transoperative bleeding was 78.9 ± 5.7 ml (range between 10 and 200 ml), mean operative time was 82 min (range 75-132 min), and hospital stay was less than 24 hours (90.90%). Surgical conversion was performed in 4.54% of cases. Conclusions: Morbidly obese patients may benefit from the laparoscopic approach for the treatment and laparoscopic surgical staging of endometrial carcinoma, which decreases morbidity and hospital stay.

Introdução: A cirurgia, em pacientes com obesidade mórbida, como tratamento para o câncer ginecológico é um desafio para o cirurgião e para o anestesiologista, pois está associada ao aumento de complicações intra e pós-operatórias. Objetivo: Descrever os principais resultados da cirurgia laparoscópica, em pacientes com obesidade mórbida e adenocarcinoma endometrial, tratados no Instituto Nacional de Oncología y Radiobiología (INOR) em Havana, Cuba, no período de janeiro de 2019 a março de 2020. Método: A estudo descritivo, observacional e transversal realizado em 22 pacientes com índice de massa corporal superior a 40 kg/m2 e diagnóstico de adenocarcinoma de endométrio, submetidas à cirurgia laparoscópica. Os dados primários foram obtidos por meio dos prontuários, com os quais foi criado um banco de dados em uma planilha do Microsoft Excel para sintetizar todas as informações. Resultados: Predominou a idade entre 61 a 70 anos. O adenocarcinoma endometrioide foi o mais frequente com 77,27%. O grau de diferenciação foi bem diferenciado, infiltrando menos de 50% do miométrio. O estadiamento cirúrgico predominante foi IA (72,72%). O sangramento transoperatório foi de 78,9 ± 5,7 ml (variação de 10 e 200 ml), a média do ato cirúrgico foi de 82 min (variação de 75-132 min) e o tempo de internação foi inferior a 24 horas (90,90%). A conversão cirúrgica foi realizada em 4,54% dos casos. Conclusões: Pacientes com obesidade mórbida podem se beneficiar da abordagem laparoscópica para o tratamento e estadiamento cirúrgico laparoscópico do carcinoma endometrial, o que diminui a morbidade e o tempo de internação.

Inhibitory effect of Mexican oregano (Lippia graveolens Kunth) extracts on digestive enzymes in vitro, and beneficial impact on carbohydrates and lipids absorption in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Mexican oregano inhibits digestive enzymes in vitro its effect on the absorption of carbohydrates and lipids in vivo has not been addressed. AIM OF THE STUDY: Assess the effect of Mexican oregano (Lippia graveolens Kunth) on carbohydrates and lipids absorption in vivo. The antioxidant activity also was investigated. MATERIALS AND METHODS: Enzymatic inhibitory action of lipase, α-amylase, and α-glucosidase was evaluated in vitro. Oral lipid (OLTT) and starch tolerance tests (OSTT) were conducted with L. graveolens acetone (O-A) and ethanol (O-E) extracts (at 102 mg/kg body weight equivalent to a 1 g human doses) in male Wistar rats. The antioxidant activity was evaluated through inhibition of lipid peroxidation and scavenging radical. RESULTS: Both extracts exhibited higher inhibitory median concentration (IC50) of lipase activity (1.9 µg/µL for O-E and 1.8 µg/µL for O-A) than the positive control (Orlistat) (0.07 µg/µL). The IC50 of α-amylase was higher (41.8 µg/µL for O-E and 25.2 µg/µL for O-A) than the Acarbose (2.5 µg/µL); while α-glucosidase results showed not statistically differences between groups (∼1.7 µg/µL). The OLTT results showed that both extracts significantly reduced serum triglycerides (∼147 mg/dL for O-E and ∼155 mg/dL for O-A) as compared with negative control group (only lipid load). In the OSTT, glucose levels showed a significant decrease (∼31 mg/dL for O-E and ∼17 mg/dL for O-A) than the negative control group (only starch load). About in vitro antioxidant evaluation, not statistically differences between extracts and positive control (Trolox) were observed for scavenged free radicals (∼2.0 µg/µL); whereas O-A inhibited lipid peroxidation similar to the Trolox (∼0.8 µg/µL IC50). The main chemical composition of both extracts was coumaric acid, luteolin, rutinoside, naringenin, and carvacrol. CONCLUSIONS: Both extracts reduce lipid absorption; whereas O-E decreases carbohydrate absorption in vivo. Both extracts inhibit lipid peroxidation and scavenging free radicals in vitro.

Cytotoxic Effects on Breast Cancer Cell Lines of Chalcones Derived from a Natural Precursor and Their Molecular Docking Analysis.

This study aimed to determine the in vitro cytotoxicity and understand possible cytotoxic mechanisms via an in silico study of eleven chalcones synthesized from two acetophenones. Five were synthesized from a prenylacetophenone isolated from a plant that grows in the Andean region of the Atacama Desert. The cytotoxic activity of all the synthesized chalcones was tested against breast cancer cell lines using an MTT cell proliferation assay. The results suggest that the prenyl group in the A-ring of the methoxy and hydroxyl substituents of the B-ring appear to be crucial for the cytotoxicity of these compounds. The chalcones 12 and 13 showed significant inhibitory effects against growth in MCF-7 cells (IC50 4.19 ± 1.04 µM and IC50 3.30 ± 0.92 µM), ZR-75-1 cells (IC50 9.40 ± 1.74 µM and IC50 8.75 ± 2.01µM), and MDA-MB-231 cells (IC50 6.12 ± 0.84 µM and IC50 18.10 ± 1.65 µM). Moreover, these chalcones showed differential activity between MCF-10F (IC50 95.76 ± 1.52 µM and IC50 95.11 ± 1.97 µM, respectively) and the tumor lines. The in vitro results agree with molecular coupling results, whose affinity energies and binding mode agree with the most active compounds. Thus, compounds 12 and 13 can be considered for further studies and are candidates for developing new antitumor agents. In conclusion, these observations give rise to a new hypothesis for designing chalcones with potential cytotoxicity with high potential for the pharmaceutical industry.

Lanthanide SMMs Based on Belt Macrocycles: Recent Advances and General Trends.

Enhancement of axial magnetic anisotropy is the central objective to push forward the performance of Single-Molecule Magnet (SMM) complexes. In the case of mononuclear lanthanide complexes, the chemical environment around the paramagnetic ion must be tuned to place strongly interacting ligands along either the axial positions or the equatorial plane, depending on the oblate or prolate preference of the selected lanthanide. One classical strategy to achieve a precise chemical environment for a metal centre is using highly structured, chelating ligands. A natural approach for axial-equatorial control is the employment of macrocycles acting in a belt conformation, providing the equatorial coordination environment, and leaving room for axial ligands. In this review, we present a survey of SMMs based on the macrocycle belt motif. Literature systems are divided in three families (crown ether, Schiff-base and metallacrown) and their general properties in terms of structural stability and SMM performance are briefly discussed.

Design, Synthesis, In Silico Studies and Inhibitory Activity towards Bcr-Abl, BTK and FLT3-ITD of New 2,6,9-Trisubstituted Purine Derivatives as Potential Agents for the Treatment of Leukaemia.

We report 31 new compounds designed, synthesized and evaluated on Bcr-Abl, BTK and FLT3-ITD as part of our program to develop 2,6,9-trisubstituted purine derivatives as inhibitors of oncogenic kinases. The design was inspired by the chemical structures of well-known kinase inhibitors and our previously developed purine derivatives. The synthesis of these purines was simple and used a microwave reactor for the final step. Kinase assays showed three inhibitors with high selectivity for each protein that were identified: 4f (IC50 = 70 nM for Bcr-Abl), 5j (IC50 = 0.41 µM for BTK) and 5b (IC50 = 0.38 µM for FLT-ITD). The 3D-QSAR analysis and molecular docking studies suggested that two fragments are potent and selective inhibitors of these three kinases: a substitution at the 6-phenylamino ring and the length and volume of the alkyl group at N-9. The N-7 and the N-methyl-piperazine moiety linked to the aminophenyl ring at C-2 are also requirements for obtaining the activity. Furthermore, most of these purine derivatives were shown to have a significant inhibitory effect in vitro on the proliferation of leukaemia and lymphoma cells (HL60, MV4-11, CEM, K562 and Ramos) at low concentrations. Finally, we show that the selected purines (4i, 5b and 5j) inhibit the downstream signalling of the respective kinases in cell models. Thus, this study provides new evidence regarding how certain chemical modifications of purine ring substituents provide novel inhibitors of target kinases as potential anti-leukaemia drugs.

Substituted Purines as High-Affinity Histamine H3 Receptor Ligands.

Continuing with our program to obtain new histamine H3 receptor (H3R) ligands, in this work we present the synthesis, H3R affinity and in silico studies of a series of eight new synthetically accessible purine derivatives. These compounds are designed from the isosteric replacement of the scaffold presented in our previous ligand, pyrrolo[2,3-d]pyrimidine ring, by a purine core. This design also considers maintaining the fragment of bipiperidine at C-4 and aromatic rings with electron-withdrawing groups at N-9, as these fragments are part of the proposed pharmacophore. The in vitro screening results show that two purine derivatives, 3d and 3h, elicit high affinities to the H3R (Ki values of 2.91 and 5.51 nM, respectively). Both compounds are more potent than the reference drug pitolisant (Ki 6.09 nM) and show low toxicity with in vitro models (IC50 > 30 µM on HEK-293, SH-SY5Y and HepG2 cell lines). Subsequently, binding modes of these ligands are obtained using a model of H3R by docking and molecular dynamics studies, thus determining the importance of the purine ring in enhancing affinity due to the hydrogen bonding of Tyr374 to the N-7 of this heterocycle. Finally, in silico ADME properties are predicted, which indicate a promising future for these molecules in terms of their physical−chemical properties, absorption, oral bioavailability and penetration in the CNS.

Economic appraisal of using genetics to control Streptococcus agalactiae in Nile tilapia under cage and pond farming system in Malaysia.

Disease outbreaks have been seen as the major threat to sustainable aquaculture worldwide. Injectable vaccines have been one of the few strategies available to control the diseases, however, the adoption of this technology globally is limited. Genetic selection for disease resistance has been proposed as the alternative strategy in livestock and aquaculture. Economic analysis for such strategies is lacking and this study assesses the economic worth of using tilapia fingerlings resistant to Streptococcosis in both cage and pond production systems. The paper also assesses the profitability of paying the higher price for such fingerlings. Partial-budgeting was used to develop a stochastic simulation model that considers the benefits and costs associated with the adoption of tilapia fingerlings resistant to Streptococcosis at the farm level, in one production cycle. In both ponds and cage production systems, the use of genetically selected Streptococcus resistant tilapia fingerlings was found to be profitable where Streptococcus infection is prevalent. In the cages and ponds where Streptococcus related mortality was ≥ 10%, the Nile tilapia aquaculture was found to be profitable even if the amount paid for genetically selected Streptococcus resistant tilapia fingerlings was 100% higher than the amount paid for standard fingerlings.

Transferencia tendinosa del tibial posterior en pie caído por lesión del nervio peroneo común / Tendon transfer of the posterior tibial in fallen foot due to lesion of the common peroneal nerve i:en

Se describe el caso clínico de un paciente de 34 años de edad, con antecedente de salud, atendido en la consulta intermunicipal de II Frente, provincia de Santiago de Cuba, por presentar, desde hacía 8 meses, una lesión en el nervio peroneo común, en la cara lateral del tercio superior de la pierna derecha, a causa de una mordida de cerdo, la cual no fue diagnosticada inicialmente, sino que se trató como una herida sin lesión neurológica. Se realizó proceder quirúrgico, consistente en una transposición tendinosa del músculo tibial posterior. Se inmovilizó el pie con una férula de yeso por 15 días, se le retiró la sutura a las 6 semanas y se indicó rehabilitación. A las 12 semanas comenzó a caminar sin dificultad y logró reincorporarse a sus actividades cotidianas.

The case report of a 34 years patient with health history is described. He was assisted in the intermunicipal visit of II Frente, province of Santiago de Cuba, due to a lesion in the common peroneal nerve during 8 months, in the lateral face of the superior third of the right leg, because of a pig bite, which was not diagnosed initially, but instead it was treated as a wound without neurological lesion. A surgical procedure was carried out, with a tendon transposition of the posterior tibial muscle. The foot was immobilized with a plaster splint for 15 days, the suture was removed 6 weeks later and rehabilitation was indicated. Twelve weeks later he began to walk without difficulty and he was able to return to his daily activities.

Arsenate Removal from Aqueous Media Using Chitosan-Magnetite Hydrogel by Batch and Fixed-Bed Columns.

The removal of arsenate ions from aqueous solutions at near-neutral pH was carried out using chitosan-magnetite (ChM) hydrogel beads in batch systems. Equilibrium isotherms and kinetic studies are reported. Obtained equilibrium and kinetic data were fitted to mathematical models, estimating model parameters by non-linear regression analysis. Langmuir model was found to best fit equilibrium data; a maximum adsorption capacity of 66.9 mg As/g was estimated at pH 7.0. Pseudo-first order kinetic model was observed to best fit kinetic data. The pH of the solution was observed to increase with increasing contact time, which is attributed to protonation of amine groups present in the hydrogel. Protonation of functional groups in the ChM sorbent yields a higher number of active sites for arsenate removal, being as this a process that can't be overlooked in future applications of ChM hydrogel for the removal or arsenate ions. Chitosan-magnetite and ChM-arsenate interactions were determined by XPS. Arsenate removal using fixed-bed column packed with ChM was carried out, reporting a non-ideal behavior attributed to pH increase of the effluent caused by proton transfer to ChM hydrogels.

Heart rate variability in children: methodological issues and clinical applications. / Variabilidad del ritmo cardíaco en pediatría: aspectos metodológicos y aplicaciones clínicas.

Heart rate variability (HRV) corresponds to variations in heart rate or beat-beat time interval. This parameter reflects the status of the autonomic mechanisms of cardiovascular control, which may be influenced by changes characteristic of the life cycle of people, sedentary lifestyle, and various disease processes that directly or indirectly generate changes in the HRV and shift the autonomic balance, either towards greater sympathetic or parasympathetic influence on the heart. These antecedents support the use of HRV indices for the diagnosis and monitoring of various nosological entities in adults. However, there has been limited progress in the study of temporal variations in heart rhythm in the pediatric population. This article aims to describe the physiological and technical aspects of HRV in the pediatric population to provide a background that allows optimizing the application of these parameters in this age group.

La variabilidad del ritmo cardíaco (VRC) corresponde a las variaciones temporales de la frecuencia cardíaca o del intervalo latido-latido. Este parámetro refleja el estado de los mecanismos autonómicos de control cardiovascular. Los cambios propios del ciclo vital de las personas, el sedentarismo y diversos procesos de enfermedad han mostrado inducir cambios en la VRC y desplazar el balance autonómico hacia una mayor influencia simpática o parasimpática sobre el corazón. Estos antecedentes apoyan el uso de los índices de VRC para el diagnóstico y seguimiento de diversas entidades nosológicas en el adulto. Sin embargo, en la población pediátrica ha existido un limitado avance en el estudio de las variaciones temporales del ritmo cardíaco. Este artículo tiene por objetivo describir los aspectos fisiológicos y técnicos de la VRC en población pediátrica. El propósito es aportar antecedentes que permitan optimizar la aplicación de estos parámetros en este grupo etario.