Sex Differences in Left Bundle Branch Area Pacing Versus Biventricular Pacing for Cardiac Resynchronization Therapy.

BACKGROUND: Women respond more favorably to biventricular pacing (BIVP) than men. Sex differences in atrioventricular and interventricular conduction have been described in BIVP studies. Left bundle branch area pacing (LBBAP) offers advantages due to direct capture of the conduction system. We hypothesized that men could respond better to LBBAP than BIVP. OBJECTIVES: This study aims to describe the sex differences in response to LBBAP vs BIVP as the initial cardiac resynchronization therapy (CRT). METHODS: In this multicenter prospective registry, we included patients with left ventricular ejection fraction ≤35% and left bundle branch block or a left ventricular ejection fraction ≤40% with an expected right ventricular pacing exceeding 40% undergoing initial CRT with LBBAP or BIVP. The composite primary outcome was heart failure-related hospitalization and all-cause mortality. The primary safety outcome included all procedure-related complications. RESULTS: There was no significant difference in the primary outcome when comparing men and women receiving LBBAP (P = 0.46), whereas the primary outcome was less frequent in women in the BIVP group than men treated with BIVP (P = 0.03). The primary outcome occurred less frequently in men undergoing LBBAP (29.9%) compared to those treated with BIVP (46.5%) (P = 0.004). In women, the incidence of the primary endpoint was 24.14% in the LBBAP group and 36.2% in the BIVP group; however, this difference was not statistically significant (P = 0.23). Complication rates remained consistent across all groups. CONCLUSIONS: Men and women undergoing LBBAP for CRT had similar clinical outcomes. Men undergoing LBBAP showed a lower risk of heart failure-related hospitalizations and all-cause mortality compared to men undergoing BIVP, whereas there was no difference between LBBAP and BIVP in women.

Management of urinary stones: state of the art and future perspectives by experts in stone disease.

AIM: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up:  Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies. PROPHYLAXIS: Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most "high-risk" patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched. FUTURE RESEARCH: Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation.

Natural proliferative phase frozen embryo transfer-a new approach which may facilitate scheduling without hindering pregnancy outcomes.

STUDY QUESTION: How does a natural proliferative phase (NPP) strategy for frozen embryo transfer (FET) compare with the conventional artificial (AC) and natural (NC) endometrial preparation protocols in terms of live birth rates (LBR)? SUMMARY ANSWER: This study supports the hypothesis that, just as for NC, NPP-FET may be a superior alternative to AC in terms of LBR. WHAT IS KNOWN ALREADY: Although FETs are increasing worldwide, the optimal FET protocol is still largely controversial. Despite recent evidence supporting a possibly higher efficacy and safety of NC FETs, their widespread use is limited by the difficulties encountered during cycle monitoring and scheduling. STUDY DESIGN, SIZE, DURATION: In this single center retrospective cohort study, we describe the NPP-FET protocol, in which vaginal progesterone is initiated during the proliferative phase as soon as an endometrium with a thickness of at least 7 mm is identified and ovulation is ruled out, regardless of mean diameter of the dominant follicle. PARTICIPANTS/MATERIALS, SETTING, METHODS: For comparison, we considered all blastocyst stage FET cycles preformed at a private infertility center between January 2010 and June 2022, subdivided according to the following subgroups of endometrial preparation: AC, NPP, and NC. We performed multivariable generalized estimating equations regression analysis to account for the following potential confounding variables: oocyte age at retrieval, oocyte source (autologous without preimplantation genetic testing for aneuploidies (PGT-A) versus autologous with PGT-A versus donated), number of oocytes retrieved/donated, embryo developmental stage (Day 5 versus Day 6), number of embryos transferred, quality of the best embryo transferred, and year of treatment. The main outcome measure was LBR. The secondary outcomes included hCG positive, clinical pregnancy and miscarriage rates, and the following perinatal outcomes: first trimester bleeding, second/third trimester bleeding, preterm rupture of membranes, gestational diabetes, gestational hypertensive disorders (GHD), and gestational age at delivery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 5791 FET cycles were included in this analysis (2226 AC, 349 NPP, and 3216 NC). The LBR for FET was lower in the AC subgroup when compared to the NPP and NC (38.4%, 49.1%, and 45.2%, respectively; P < 0.01 AC versus NPP and AC versus NC). The rates of miscarriage were also lower in the NPP and NC subgroups when compared to AC (19.7%, 25.0%, and 34.9%, respectively; P < 0.01 NPP versus AC and NC versus AC). Considering perinatal outcomes, NPP-FET and NC were associated with a significantly lower first trimester bleeding compared to AC (17.3%, 14.7%, and 37.6%, respectively; P < 0.01 NPP versus AC and NC versus AC). Additionally, NC was associated with a lower rate of GHD when compared with AC (8.6% versus 14.5%, P < 0.01), while the rate following NPP-FET was 9.4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design. Moreover, there was also a low number of patients in the NPP subgroup, which may have led the study to be underpowered to detect clinically relevant differences between the subgroups. WIDER IMPLICATIONS OF THE FINDINGS: Our study posits that the NPP-FET protocol may be an effective and safe alternative to both NC and AC, while still allowing for enhanced practicality in patient follow-up and FET scheduling. Further investigation on NPP-FET is warranted, with prospective studies including a larger and more homogeneous subsets of patients. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the IVI-RMA-Lisbon (2008-LIS-053-CG). The authors did not receive any funding for this study. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

The potential impact of PCV-13, PCV-15 and PCV-20 vaccines in Colombia.

PURPOSE: To provide information about which pneumococcal vaccine could have greater coverage in Colombia. METHODS: This is a retrospective analysis of patients diagnosed with invasive pneumococcal disease (IPD) between 2015 and 2019 in Bogotá, Colombia. We compared the theoretical serotype coverage of the available anti-pneumococcal vaccines (i.e., PCV-10, PCV-10 SII, PCV-13, PCV-15, PCV-20, PCV-21, PCV24, PPSV-23) and the non-vaccine-covered serotypes stratified by age. RESULTS: 690 IPD cases were included. In children ≤5 y/o, of the approved vaccines PCV-20 showed the most theoretical protection (71.3 % [149/209]), while in adults aged 18-64 y/o was PCV-20 (61.8 % [164/265]), and in those ≥65 y/o was PPSV-23 (58.1 % [100/172]) followed by PCV-20 (55.2 % [95/172]). The non-covered serotypes represented one-third of the cohort (33.9 % [234/690]), being 6C (20.5 % [48/234]), 15A (12.8 % [30/234]), and 23A (11.5 % [27/234]) the most prevalent. CONCLUSION: Introducing PCV-20 for children and PCV-20 along with a PPSV-23 booster in adults may reduce IPD frequency in all ages in Colombia. The inclusion of non-covered serotypes is required for future vaccines.

Linear Polyethyleneimine-Based and Metal Organic Frameworks (DUT-67) Composite Hydrogels as Efficient Sorbents for the Removal of Methyl Orange, Copper Ions, and Penicillin V.

This research explores the integration of DUT-67 metal organic frameworks into polyethyleneimine-based hydrogels to assemble a composite system with enough mechanical strength, pore structure and chemical affinity to work as a sorbent for water remediation. By varying the solvent-to-modulator ratio in a water-based synthesis path, the particle size of DUT-67 was successfully modulated from 1 µm to 200 nm. Once DUT-67 particles were integrated into the polymeric hydrogel, the composite hydrogel exhibited enhanced mechanical properties after the incorporation of the MOF filler. XPS, NMR, TGA, FTIR, and FT Raman studies confirmed the presence and interaction of the DUT-67 particles with the polymeric chains within the hydrogel network. Adsorption studies of methyl orange, copper(II) ions, and penicillin V on the composite hydrogel revealed a rapid adsorption kinetics and monolayer adsorption according to the Langmuir's model. The composite hydrogel demonstrated higher adsorption capacities, as compared to the pristine hydrogel, showcasing a synergistic effect, with maximum adsorption capacities of 473 ± 21 mg L-1, 86 ± 6 mg L-1, and 127 ± 4 mg L-1, for methyl orange, copper(II) ions, and penicillin V, respectively. This study highlights the potential of MOF-based composite hydrogels as efficient adsorbents for environmental pollutants and pharmaceuticals.

Hallazgos nasosinusales por tomografía computada en dacriocistitis crónica pediátrica.

OBJECTIVE: To evaluate the preoperative tomographic characteristics of the nose and paranasal sinuses of children with chronic dacryocystitis. METHOD: Prospective, observational, cross-sectional, and descriptive study. CT scans of the paranasal sinuses of patients candidates for endoscopic dacryocystorhinostomy were evaluated for two years. Demographic characteristics, radiological findings, inflammatory processes and anatomical variants were identified using the Lund-Mackay classification. Statistic analysis. Stata 10.0, descriptive analysis, Student's t: mean difference and χ2. Logistic studies to estimate the probability between variables. RESULTS: 27 men and 11 women (n = 38) were included. Of these, 22 had unilateral and 16 bilateral nasolacrimal duct involvement. Lund-Mackay score range: 2-20. Eleven patients had associated pathology. The most affected were anterior and maxillary ethmoidal sinus (69%), osteomeatal complex (68%), posterior ethmoidal (51%). Patients with severe rhinosinusitis are 12 times more likely to develop dacryocystitis than patients with < 12 points. Men presented greater severity, affectation, and clinical repercussion. CONCLUSIONS: There is radiological rhinosinusal involvement in dacryocystitis, which must be evaluated and treated preoperatively to avoid postoperative complications or reinfections.

OBJETIVO: Evaluar las características tomográficas preoperatorias de la nariz y los senos paranasales de niños con dacriocistitis crónica. MÉTODO: Estudio prospectivo, observacional, transversal y descriptivo. Se evaluaron tomografías de senos paranasales de pacientes candidatos a dacriocistorrinostomía endoscópica, durante 2 años. Se identificaron características demográficas, hallazgos radiológicos, procesos inflamatorios y variantes anatómicas, utilizando la clasificación Lund-Mackay. Análisis estadístico con Stata 10.0, análisis descriptivo con t de Student: diferencia medias y χ2. Estudios logísticos para estimar la probabilidad entre variables. RESULTADOS: Se incluyeron 27 hombres y 11 mujeres (n = 38). De ellos, 22 tenían afección del conducto nasolagrimal unilateral y 16 bilateral. Rango de puntuación de Lund-Mackay: 2-20. Once pacientes tuvieron patología asociada. Seno etmoidal anterior y maxilar más afectados (69%), complejo osteomeatal (68%), etmoidal posterior (51%). La probabilidad de que los pacientes con rinosinusitis grave puedan presentar dacriocistitis es 12 veces mayor que en los pacientes con < 12 puntos. Los hombres presentaron mayor gravedad, afectación y repercusión clínica. CONCLUSIONES: Existe afección rinosinusal radiológica en la dacriocistitis, que debe ser evaluada y tratada en el preoperatorio para evitar complicaciones o reinfecciones posquirúrgicas.

Shared Hydrogen Atom Location and Chemical Composition in Picolinic Acid and Pyridoxal Hydrochloride Derivatives Determined by X-ray Crystallography.

Three new single-crystal structures were isolated for picolinic acid (2), the trifluoroacetate salt of picolinic acid (1), and pyridoxal hydrochloride (3). These compounds displayed unconventional crystallographic features that must be considered when structural refinements are carried out. Thus, the generated Fourier differences map obtained with the diffraction data collected at 100 K was crucial to visualize electron densities, which were balanced by either one hydrogen atom or a hydrogen atom with an occupancy factor of 1/2 located between either two carboxylate moieties, two phenolic oxygen atoms, or two pyridinic nitrogen atoms. Moreover, NMR studies were conducted to analyze the bulk chemical composition of single crystals of 2-pyridinecarboxylic acid obtained from the gem-diol/hemiacetal forms and the polymerization products after the treatment of 2-pyridinecarboxaldehyde with TFA:H2O (1) or a diluted Cu(NO3)2 solution (2). The quantitative yield of the pyridoxal hydrochloride crystalline material (3) obtained from a diluted CuCl2 solution was exhaustively characterized by solid-state NMR methods. These methods allowed the resolution of the signals corresponding to the protons of the hydroxyl moiety of the intramolecular hemiacetal group and the phenolic hydrogen. Theoretical calculations using DFT methods were done to complement the atomic location of the hydrogen atoms obtained from the X-ray analysis.

Occurrence of entomopathogenic hypocrealean fungi in mosquitoes and their larval habitats in Central Brazil, and activity against Aedes aegypti.

Collecting entomopathogenic fungi associated with mosquitoes and studies on their activity against mosquito developmental stages will improve the understanding of their potential as agents to control important mosquito vectors. Twenty-one strains of entomopathogenic fungi affecting mosquitoes in Central Brazil were studied: 7 of Beauveria bassiana, 7 of Metarhizium humberi, 3 of M. anisopliae, 2 of Cordyceps sp. and one each of Akanthomyces saksenae and Simplicillium lamellicola. These fungi were isolated from field-collected mosquito adults (3 strains) or larvae (a single strain); the other 17 strains were isolated from laboratory-reared Aedes aegypti sentinel larvae set out in partially immersed cages placed in diverse small- to middle-sized aquatic mosquito habitats in or close to areas with secondary tropical forest. The frequent recovery of normally soil-borne Metarhizium spp. and B. bassiana from aquatic habitats is notable. Our laboratory findings indicated that M. anisopliae IP 429 and IP 438 and M. humberi IP 421 and IP 478 were highly active against immature stages and, together with M. anisopliae IP 432, also against adults. These strains appear to be the most promising candidates to develop effective control strategies targeting the different developmental stages of A. aegypti, the most important vector of viral diseases in humans in the tropics.

Clonostachys spp., natural mosquito antagonists, and their prospects for biological control of Aedes aegypti.

Aedes aegypti (Linnaeus, 1762) is an important vector of arboviruses in the tropics and subtropics. New control strategies based on natural enemies such as entomopathogenic fungi are of utmost importance, and the present study reports the first isolation of Clonostachys spp. (Hypocreales: Bionectriaceae) from mosquitoes and their activity against A. aegypti. Entomopathogenic fungi were surveyed in central Brazil using A. aegypti larvae as sentinels and, also, a CDC light trap. Clonostachys eriocamporesii R.H. Perera & K.D. Hyde, 2020 (IP 440) and Clonostachys byssicola Schroers, 2001 (IP 461) were identified by sequence analysis of the nuclear ribosomal internal transcribed spacer gene, and tested against eggs, larvae, and adults. Both strains were highly active against A. aegypti third instar larvae, with mortalities ≥ 80% at 107 conidia/mL after 5 days but distinctly less active against eggs and adults. This is the first report of both C. eriocamporesii and C. byssicola as naturally occurring pathogens affecting mosquitoes, and IP 440 appears to be a promising control agent against aquatic stages of A. aegypti.

Solid-State Characterization of Acetylpyridine Copper Complexes for the Activation of H2 O2 in Advanced Oxidation Processes.

This work describes the synthesis of 4-(4-AcPy) and 3-acetylpyridine (3-AcPy) copper soluble complexes for the activation of hydrogen peroxide and the concomitant generation of reactive oxygen species (ROS). Given the paramagnetic effects of copper ions in the Nuclear Magnetic Resonance (NMR) lines, we aimed at demonstrating that the combination of high-resolution 2D solid-state NMR experiments, Electron Paramagnetic Resonance (EPR), single-crystal X-ray crystallography and Density Functional Theory (DFT) calculations allows a detailed study of the chemical structure of the ligands and the surrounding metal ions. The copper complexes synthesized with CuCl2 were useful for the activation of H2 O2 during which the only ROS was the hydroxyl one, as demonstrated by EPR experiments. A removal of methyl orange (MO) azo-dye higher than 85 % was achieved in 200 minutes, combining 1.7 mM of copper complexes with 60 mM of H2 O2 and 40 µM of MO.

S, N-doped carbon dots-based cisplatin delivery system in adenocarcinoma cells: Spectroscopical and computational approach.

S and N-doped carbon dots (S-CDs and N-CDs) and their cisplatin (cis-Pt) derivatives. (S-CDs@cis-Pt and N-CDs@cis-Pt) were tested on two ovarian cancer cell lines: A2780 and A2780 cells resistant to cis-Pt (A2780R). Several spectroscopic techniques were employed to check S-CDs@cis-Pt and N-CDs@cis-Pt: solid- and solution-state nuclear magnetic resonance, matrix-assisted laser desorption, ionization time-of-flight mass spectrometry, and X-ray photoelectron spectroscopy. In addition, synchrotron-based Fourier Transformed Infrared spectro-microscopy was used to evaluate the biochemical changes in cells after treatment with cis-Pt, S-CDs, N-CDs, or S-CDs@cis-Pt and N-CDs@cis-Pt, respectively. Computational chemistry was applied to establish the model for the most stable bond between S-CDs and N-CDs and cis-Pt. The results revealed the successful modification of S-CDs and N-CDs with cis-Pt and the formation of a stable composite system that can be used for drug delivery to cancer cells and likewise to overcome acquired cis-Pt resistance. Nanoparticle treatment of A2780 and A2780R cells led to the changes in their structure of lipids, proteins, and nucleic acids depending on the treatment. The results showed the S-CDs@cis-Pt and N-CDs@cis-Pt might be used in the combination with cis-Pt to treat the adenocarcinoma, thus having a potential to be further developed as drug delivery systems.

Are Radial Pressure Waves Effective for the Treatment of Moderate or Mild to Moderate Erectile Dysfunction? A Randomized Sham Therapy Controlled Clinical Trial.

INTRODUCTION: Radial wave therapy is commercialized as an option for the management of erectile dysfunction. However, the mechanism of action of the radial waves differs substantially from shock waves, so the evidence gathered for shock wave therapy cannot be extrapolated, and there are very few clinical trials with the radial wave. AIM: To assess the efficacy and safety of radial wave therapy compared with sham therapy for the treatment of moderate and mild to moderate erectile dysfunction. METHODS: A randomized, double-blind, sham-controlled clinical trial was realized. Eighty patients with moderate erectile dysfunction, without sickle cell anemia, anticoagulation treatment, comorbidities, or conditions associated with secondary erectile dysfunction were included. The efficacy and safety were assessed at 6 and 10 weeks after randomization. Patients were randomized 1:1 to 1 of 2 arms: (i) 6 weekly sessions of radial wave therapy (RW group) or (ii) 6 weekly sessions of sham therapy (control group). All patients received sildenafil 25 mg. OUTCOME: The primary outcome was the mean change in the International Index of Erectile Function - Erectile Function (IIEF-EF) domain score at 6 weeks after randomization. RESULTS: Eighty men were randomized. The average baseline IIEF-EF score was 16.3 (Standard Deviation - SD 3.2), and the median baseline Erection Hardness Score (EHS) was 3 (IQR 1). At 6 weeks after randomization, the mean change in the IIEF-EF score was 3.4 (95% confidence interval [CI] 1.5-5.2) in the RW group and 4.2 (95% CI 2.5-5.9) in the control group. No differences were observed between groups (P value =.742). No change was observed in the median EHS score in the evaluations. No serious adverse events occurred in 2 (5%) patients after radial wave therapy, and in 1 (2.5%) patient after sham therapy. CLINICAL IMPLICATIONS: Knowledge of the effectiveness of radial waves protocols used for the treatment of moderate erectile dysfunction, helps doctors and patients in making decisions about the use of this therapy. STRENGTHS & LIMITATIONS: One strength is conducting the study with high methodological standards to minimize risk biases. Our results are limited to the evaluation of 1 specific protocol in moderate and mild to moderate erectile dysfunction. CONCLUSIONS: No difference was found in this study between men with moderate and mild to moderate erectile dysfunction treated with radial waves and men treated with placebo sham therapy. Studies with different protocols of radial waves are necessary. Sandoval-Salinas C, Saffon JP, Martínez JM, et al. Are Radial Pressure Waves Effective for the Treatment of Moderate or Mild to Moderate Erectile Dysfunction? A Randomized Sham Therapy Controlled Clinical Trial. J Sex Med 2022;19:738-744.

Sistema endocannabinoide y cannabidiol en el manejo del dolor en perros: revisión narrativa

Introducción: la marihuana (Cannabis sativa L.) es una planta originaria de Asia cada vez más reconocida por su valor terapéutico en la medicina humana y veterinaria. Contiene una gran cantidad de componentes entre los que destacan los fitocannabinoides, de los cuales los más representativos son el delta-9-tetrahidrocannabinol (THC) y Cannabidiol (CBD) que se acoplan respectivamente a los receptores CB1 y CB2 en el sistema endocannabinoide que es un sistema neurotransmisor entre células que regula varios procesos en los vertebrados como memoria, dolor, inflamación, apetito y procesos inmunológicos entre otros. Objetivo: realizar una síntesis narrativa del sistema endocannabinoide y cannabidiol en el manejo del dolor en perros, a partir de la búsqueda de publicaciones en bases de datos electrónica PubMed, NCBI, SciELO, Science Direct, Dialnet, Google y Google Académico. Resultados: el CBD es el principal cannabinoide utilizado en la terapia del manejo del dolor en perros por sus propiedades analgésicas y carencia de efectos psicoactivos. Conclusión: se evidencia la necesidad de realizar más investigaciones con ensayos clínicos controlados sobre el uso terapéutico del cannabidiol, que tengan validez interna y externa, con poblaciones más significativas en la especie de interés.

SUMMARY Introduction: marijuana (CannabissativaL.) is a plant native to Asia that is increasingly recognized for its therapeutic value in human and veterinary medicine. It contains a large number of components among which the phytocannabinoids stand out, of which the most representative are delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) that are coupled respectively to the CB1 and CB2 receptors in the endocannabinoid system, which is a neurotransmitter system between cells that regulates various processes in vertebrates such as memory, pain, inflammation, appetite and immune processes among others. Aim: to carry out a narrative synthesis of the endocannabinoid and cannabidiol system in the management of pain in dogs, from the search of publications in electronic databases PubMed, NCBI, SciELO, Science Direct, Dialnet, Google and Google Scholar. Results: CBD is the main cannabinoid used in pain management therapy in dogs due to its analgesic proper-ties and lack of psychoactive effects. Conclusion: there is evidence of the need for more research with controlled clinical trials on the therapeutic use of cannabidiol, which have internal and external validity, with more significant populations in the species of interest.

Introdução: a maconha (Cannabis sativa L.) é uma planta nativa da Ásia que é cada vez mais reconhecida por seu valor terapêutico na medicina humana e veterinária. Ele contém muitos componentes entre os quais se destacam os fitocanabinóides, dos quais os mais representativos são delta-9-tetrahidrocanabinol (THC) e Canabidiol (CBD) que estão acoplados respectivamente aos receptores CB1 e CB2 no sistema endocanabinóide, que é um sistema neurotransmissor entre as células que regula vários processos nos vertebrados, como memória, dor, inflamação, apetite e processos imunológicos, entre outros. Objetivo: realizar uma síntese narrativa do sistema endocanabinoide e canabidiol no manejo da dor em cães, a partir da busca de publicações nas bases de dados eletrônicas PubMed, NCBI, SciELO, Science Direct, Dialnet, Google e Google Scholar. Resultados: O CBD é o principal canabinoide utilizado na terapia de controle da dor em cães devido às suas propriedades analgésicas e ausência de efeitos psicoativos. Conclusão: há evidências da necessidade de mais pesquisas com ensaios clínicos controlados sobre o uso terapêutico do canabidiol, que tenham validade interna e externa, com populações mais significativas nas espécies de interesse.

Efficacy of focal applications of a mycoinsecticide to control Aedes aegypti in Central Brazil.

Entomopathogenic fungi can achieve important innovative outcomes for integrated mosquito control especially of Aedes aegypti, the key vector of arboviruses to humans in the tropics and subtropics. This study sought to design and to develop a simple dissemination device to attract and to infect gravid A. aegypti adults with a granular formulation of the ascomycete Metarhizium humberi IP 46, and to validate this device in the laboratory as well as in semi-field and field conditions. Hydrogel (polyacrylamide potassium polyacrylate) was confirmed to be a suitable substitute for water used in the device that attracted gravid females under field conditions. Females laid eggs on black polyethylene terephthalate carpet fixed in the device that also proved to be a suitable substrate for a granular formulation of fungal microsclerotia and/or conidia. The plastic device (29.5 cm high) was divided into a lower closed compartment with a water reservoir and an upper, laterally open but covered compartment with continuously hydrated gel and the fungal formulation attached to the carpet. The uppermost compartment permitted free circulation of mosquito adults. The device attracted both male and female A. aegypti. The fungal formulations of IP 46 propagules tested in the device were effective against adults in laboratory, semi-field, and field settings. Findings in the laboratory, semi-field, and especially in field conditions strengthen the value and utility of this innovative device for focal applications of a mycoinsecticide against this important mosquito vector.Key points• Low-cost and simple disseminating device for focal control of Aedes aegypti.• Granulized Metarhizium humberi IP 46 and hydrogel yield extended control.• Findings in field tests strengthen benefit of the device for focal application.

Pulmonary involvement in patients with juvenile systemic sclerosis / Afección pulmonar en pacientes con esclerosis sistémica juvenil

Abstract Background: Pulmonary involvement in juvenile systemic sclerosis (JSSc) is rare in children and contributes to morbimortality. This study aimed to describe the pulmonary function and clinical, radiologic, and tomographic findings in JSSc. Methods: Patients with JSSc between 5-14 years of age were included. Clinical, functional, and imaging characteristics were assessed. Patients were excluded if they showed lung disease not associated with JSSc: mixed connective tissue disease, overlap syndrome, or acute cardiopulmonary failure at the time of the study. All patients underwent physical examination, electrocardiogram, spirometry, chest X-ray, high-resolution computed tomography (HRCT) of the chest, echocardiography, lung function tests, and the 6-minute walk test (6-MWT). Descriptive statistics were employed for data analysis. Results: We studied 15 patients with the following characteristics: median age, 11 years; median since symptoms onset, 6 years; median since JSSc diagnosis and the finding of pulmonary involvement, 2 years. Lung disease was detected in 73%, interstitial lung disease (ILD) the most common affection (67%); pulmonary hypertension was found in 6.6%. 6-MWT was positive in 26.6%, forced vital capacity (FVC) was abnormal in 26.6%. No pulmonary involvement was found in four patients. Conclusions: The most frequent pulmonary affection in JSSc was ILD. Thus, early JSSc detection and periodic lung monitoring are mandatory to avoid further complications once JSSc is diagnosed.

Resumen Introducción: La afección pulmonar en la esclerosis sistémica juvenil (ESJ) es rara en niños y contribuye a la morbimortalidad. El objetivo de este estudio fue describir los hallazgos de función pulmonar, clínicos, radiológicos y tomográficos en la ESJ. Métodos: Se incluyeron pacientes con ESJ de 5-14 años de edad. Se evaluaron las características clínicas, funcionales y de imagen. No se incluyeron pacientes con enfermedades pulmonares no asociadas con ESJ en el momento del estudio: enfermedad mixta del tejido conectivo, síndrome de superposición o insuficiencia cardiopulmonar aguda. Se realizaron exploración física, electrocardiograma, espirometría, radiografía de tórax, tomografía computarizada de alta resolución de tórax, ecocardiografía, pruebas de función pulmonar y prueba de caminata de 6 minutos (PC6M). Se utilizó estadística descriptiva para el análisis de los datos. Resultados: Se estudiaron 15 pacientes con las siguientes características: mediana de edad, 11 años; mediana desde el inicio de los síntomas, 6 años; y mediana desde el diagnóstico de ESJ y hallazgo de afección pulmonar, 2 años. Se detectó enfermedad pulmonar en el 73%. La enfermedad pulmonar intersticial (EPI) fue la afección más común (67%) y se encontró hipertensión pulmonar en el 6.6%. La PC6M fue positiva en el 26.6%, y la capacidad vital forzada resultó anormal en el 26.6%. Cuatro pacientes no presentaron afección pulmonar. Conclusiones: La afección pulmonar más frecuente en la ESJ fue la EPI. La detección temprana de ESJ y la monitorización pulmonar periódica son obligatorias para evitar más complicaciones una vez diagnosticada la ESJ.

Pulmonary involvement in patients with juvenile systemic sclerosis.

Background: Pulmonary involvement in juvenile systemic sclerosis (JSSc) is rare in children and contributes to morbimortality. This study aimed to describe the pulmonary function and clinical, radiologic, and tomographic findings in JSSc. Methods: Patients with JSSc between 5-14 years of age were included. Clinical, functional, and imaging characteristics were assessed. Patients were excluded if they showed lung disease not associated with JSSc: mixed connective tissue disease, overlap syndrome, or acute cardiopulmonary failure at the time of the study. All patients underwent physical examination, electrocardiogram, spirometry, chest X-ray, high-resolution computed tomography (HRCT) of the chest, echocardiography, lung function tests, and the 6-minute walk test (6-MWT). Descriptive statistics were employed for data analysis. Results: We studied 15 patients with the following characteristics: median age, 11 years; median since symptoms onset, 6 years; median since JSSc diagnosis and the finding of pulmonary involvement, 2 years. Lung disease was detected in 73%, interstitial lung disease (ILD) the most common affection (67%); pulmonary hypertension was found in 6.6%. 6-MWT was positive in 26.6%, forced vital capacity (FVC) was abnormal in 26.6%. No pulmonary involvement was found in four patients. Conclusions: The most frequent pulmonary affection in JSSc was ILD. Thus, early JSSc detection and periodic lung monitoring are mandatory to avoid further complications once JSSc is diagnosed.

Introducción: La afección pulmonar en la esclerosis sistémica juvenil (ESJ) es rara en niños y contribuye a la morbimortalidad. El objetivo de este estudio fue describir los hallazgos de función pulmonar, clínicos, radiológicos y tomográficos en la ESJ. Métodos: Se incluyeron pacientes con ESJ de 5-14 años de edad. Se evaluaron las características clínicas, funcionales y de imagen. No se incluyeron pacientes con enfermedades pulmonares no asociadas con ESJ en el momento del estudio: enfermedad mixta del tejido conectivo, síndrome de superposición o insuficiencia cardiopulmonar aguda. Se realizaron exploración física, electrocardiograma, espirometría, radiografía de tórax, tomografía computarizada de alta resolución de tórax, ecocardiografía, pruebas de función pulmonar y prueba de caminata de 6 minutos (PC6M). Se utilizó estadística descriptiva para el análisis de los datos. Resultados: Se estudiaron 15 pacientes con las siguientes características: mediana de edad, 11 años; mediana desde el inicio de los síntomas, 6 años; y mediana desde el diagnóstico de ESJ y hallazgo de afección pulmonar, 2 años. Se detectó enfermedad pulmonar en el 73%. La enfermedad pulmonar intersticial (EPI) fue la afección más común (67%) y se encontró hipertensión pulmonar en el 6.6%. La PC6M fue positiva en el 26.6%, y la capacidad vital forzada resultó anormal en el 26.6%. Cuatro pacientes no presentaron afección pulmonar. Conclusiones: La afección pulmonar más frecuente en la ESJ fue la EPI. La detección temprana de ESJ y la monitorización pulmonar periódica son obligatorias para evitar más complicaciones una vez diagnosticada la ESJ.

Rebiopsy rate after transperineal or transrectal prostate biopsy.

BACKGROUND: In recent years, transperineal biopsies gained popularity for prostate cancer diagnosis; lower infective complications and improved sampling of the prostate are the main advantages of this technique. One question that remains unclear is whether an initial transperineal biopsy confers a lower risk for rebiopsy compared with the transrectal approach. METHODS: Six hundred seventy-one men were prospectively followed after an initial negative prostate biopsy for a median period of 49.50 (IQR: 37.62-61.17) months. Rebiopsy rate was analyzed attending to first biopsy approach (transrectal versus transperineal systematic) and clinical variables. RESULTS: Diagnostic rate was similar for transrectal and transperineal systematic biopsies. Targeted biopsies outperformed any systematic approach, and transperineal targeted in particular was superior to transrectal targeted. Rebiopsy rates were 15.4% and 5.26% for the transrectal and transperineal systematic groups, respectively. Prostate-specific antigen density and type of first biopsy were identified as rebiopsy predictors. CONCLUSION: Men undergoing transperineal systematic biopsies had a three times lower rate of rebiopsy over the study period compared with the traditional transrectal approach. This advantage could be added to the already described potential benefits of transperineal biopsies. Targeted biopsies had lower rebiopsy rate over the study period. Further innovations that decreased the cost of transperineal biopsies could favor this approach in the future.

Effect of Berberine Plus Bezafibrate Administration on the Lipid Profile of Patients with Mixed Dyslipidemia: A Pilot Clinical Trial.

To evaluate the effect of berberine (BBR) plus bezafibrate administration on the lipid profile of patients with mixed dyslipidemia. A double-blind randomized pilot clinical trial with parallel groups was carried out in 36 patients, aged 30-60 years with mixed dyslipidemia [triglycerides (TG) ≥1.7 mM and total cholesterol (TC) ≥5.2 mM]. Patients were assigned to 3 groups of 12 patients each, receiving oral administration during 90 days of BBR 500 mg t.i.d., bezafibrate 400 mg b.i.d., or BBR 500 mg t.i.d. plus bezafibrate 400 mg b.i.d, respectively. Clinical evaluation, lipid profile, glucose, creatinine, and uric acid levels were measured before and after the pharmacological intervention. Kruskal-Wallis, Wilcoxon, Mann-Whitney U, and χ2 tests were used for statistical analyses; a P ≤ .05 was considered statistically significant. BBR reduced TC levels. Bezafibrate decreased TG, TC, low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein (VLDL) concentrations. BBR plus bezafibrate decreased TG (2.6 ± 0.8 vs. 1.3 ± 0.7 mM, P = .007), TC (6.3 ± 0.7 vs. 4.6 ± 1.2 mM, P = .005), LDL-C (3.4 ± 0.6 vs. 2.2 ± 1.3 mM, P = .037), and VLDL (0.5 ± 0.2 vs. 0.2 ± 0.1 mM, P = .007) levels. Bezafibrate and BBR plus bezafibrate significantly decreased TG, TC, LDL-C, and VLDL concentrations, and thus, remitting the diagnosis of mixed dyslipidemia in 90% of the patients.

Paramagnetic solid-state NMR assignment and novel chemical conversion of the aldehyde group to dihydrogen ortho ester and hemiacetal moieties in copper(ii)- and cobalt(ii)-pyridinecarboxaldehyde complexes.

The complex chemical functionalization of aldehyde moieties in Cu(ii)- and Co(ii)-pyridinecarboxaldehyde complexes was studied. X-ray studies demonstrated that the aldehyde group (RCHO) of the four pyridine molecules is converted to dihydrogen ortho ester (RC(OCH3)(OH)2) and hemiacetal (RCH(OH)(OCH3)) moieties in both 4-pyridinecarboxaldehyde copper and cobalt complexes. In contrast, the aldehyde group is retained when the 3-pyridinecarboxaldehyde ligand is complexed with cobalt. In the different copper complexes, similar paramagnetic 1H resonance lines were obtained in the solid state; however, the connectivity with the carbon structure and the 1H vicinities were done with 2D 1H-13C HETCOR, 1H-1H SQ/DQ and proton spin diffusion (PSD) experiments. The strong paramagnetic effect exerted by the cobalt center prevented the observation of 13C NMR signals and chemical information could only be obtained from X-ray experiments. 2D PSD experiments in the solid state were useful for the proton assignments in both Cu(ii) complexes. The combination of X-ray crystallography experiments with DFT calculations together with the experimental results obtained from EPR and solid-state NMR allowed the assignment of NMR signals in pyridinecarboxaldehyde ligands coordinated with copper ions. In cases where the crystallographic information was not available, as in the case of the 3-pyridinecarboxaldehyde Cu(ii) complex, the combination of these techniques allowed not only the assignment of NMR signals but also the study of the functionalization of the substituent group.

Livestock Health and Food Chain Risk Assessment.

The EUropean FOod Risk Assessment (EU-FORA) Fellowship work programme 'Livestock Health and Food Chain Risk Assessment', funded by EFSA was proposed by the Animal and Plant Health Agency (APHA), UK. A scientist with a PhD in Food Science was selected to work within the Biomathematics and Risk Research group, under the guidance of a senior risk assessor. The programme consisted of four different modules that covered a wide range of aspects related to risk assessment (RA). The aims, activities and conclusions obtained during the year are described in this article. The learning-by-doing approach in RA allowed the fellow to discover a broad pool of methodologies, tools and applications while developing his own knowledge in RA, as well as gaining scientific network for future collaborations in the field.