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Juan Carlos Quintana-Castillo,1 Sebastián Estrada-Gómez,2 Jaiberth Antonio Cardona-Arias3 1Faculty of Medicine, Universidad Cooperativa de Colombia, Medellín, Colombia; 2Faculty of Pharmaceutical and Food Sciences, Universidad de Antioquia, Medellín, Colombia; 3School of Microbiology, Universidad de Antioquia, Medellín, ColombiaCorrespondence: Jaiberth Antonio Cardona-Arias Email jaiberthcardona@gmail.comBackground: Snakebite is an often-neglected event with a high rate of mortality and is concentrated in poor areas. We aimed to assess the economic impact and health effects of the implementation of interventions for snakebites through a systematic review of the scientific literature.Methods: Thirty search strategies were conducted in seven databases, applying PRISMA’s identification, screening, selection, and inclusion phases. The reproducibility of the selection of studies and the extraction of information were guaranteed. The methodological quality was evaluated using the Consolidated Health Economic Evaluation Reporting Standards. Qualitative synthesis and meta-analysis were performed for determining the average cost-effectiveness (ACE) for each death and disability-adjusted life years (DALY) avoided.Results: Six cost-effectiveness studies were included for the supply of antivenom (AV), taken as outcomes on days of hospitalization or in ICU, death and DALYs avoided. All studies only included institutional costs, and majority of them did not specify the analytical model or economic evaluation parameters and did not perform uncertainty analyses. The management protocol standardization with interdisciplinary attention improves ACE of AV. Cost-effectiveness ratio (CER) of treatment with AV was USD 1253 (constant value for the year 2017, adjusted by purchasing power parity) for each death avoided and USD 51 per DALY avoided.Conclusion: High cost-effectiveness of the AV treatment for snakebites was evidenced, which shows that the allocation of resources for this event should be a healthcare priority in addition to implementation of strategies that improve the access to, opportunity, and quality of hospital and pre-hospital care and reduce the cost of AV.Keywords: snake envenoming, DALYs, antivenom, cost-effectiveness

Mexican Coccoloba uvifera fruit contains polyphenols, flavonoids, and anthocyanins, while in the leaves, lupeol, α- and β-amyrin have been previously identified by HPLC. However, the low resolution by HPLC of pentacyclic triterpenes (PTs) is a limitation. Moreover, the volatile profile of C. uvifera fruit is still unknown. Therefore, this study aimed to identify PTs in C. uvifera leaf and fruit extracts by CG-MS analysis and to determine the volatile profile of C. uvifera pulp by headspace solid-phase microextraction. The results showed trimethylsilylated compounds of standards lupeol, α- and β-amyrin, indicating that the silylation reaction was suitable. These trimethylsilylated compounds were identified in leaf and fruit extracts. The fruit volatile profile revealed the presence of 278 esters, 20 terpenes, 9 aldehydes, 5 alcohols, and 4 ketones. The fruit showed a high content of esters and terpenes. Due to their flavour properties, esters are essential for the food, cosmetics, and pharmaceutics industries. Moreover, terpenes in the fruit, such as menthone, β-elemene, junipene, and β-caryophyllene have the potential as anticancer and phytopathogen agents. The results indicated that GC-MS is an alternative to HPLC approaches for identifying PTs. Besides, identifying volatile compounds in the fruit will increase the value of this plant and expand its application. Identifying PTs and volatile compounds in Mexican C. uvifera leads to a better understanding of the potential benefits of this plant. This would increase the consumption of Mexican C. uvifera fresh or as functional ingredients in nutraceutical or pharmaceutical products., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction and Aims: Fabry disease (FD) causes glycosphingolipid accumulation in the vascular endothelium, with predominantly cardiac and renal involvement. Its prevalence in patients with concomitant involvement of these two organs is unknown. The objective of the study was to determine the prevalence of FD in patients with left ventricular hypertrophy and any degree of chronic kidney disease., Patients and Methods: Patients with ventricular thickness ≥13mm and kidney disease from 29 Spanish hospitals were included. Sociodemographic variables and target organ involvement of FD were collected. Laboratory determinations of EF were carried out, with an enzymatic activity test±genetic test in men and direct genetic test in women., Results: Eight hundred ninety-eight patients with left ventricular hypertrophy and chronic kidney disease were included. The presence of heart failure and cardiorenal syndrome was common (46.1% and 40.1%). Three patients (2 men and 1 woman) were diagnosed with FD, based on the presence of a pathogenic variant in the GLA gene and classic signs of FD, resulting in a prevalence of 0.33% (CI 95% 0.06-1%). Six patients (0.66%) presented genetic variants of unknown significance, without showing classic signs of FD, while in 13 patients (3.2%) performing the blood test was impossible., Conclusions: FD is an important cause of left ventricular hypertrophy and chronic kidney disease. Genetic diagnosis is crucial for avoiding biases and ensuring accurate identification of FD, especially in women. The results support the inclusion of this disease in the differential diagnosis of patients with ventricular hypertrophy ≥13mm and chronic kidney disease., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

The improvement in survival rates in pediatric malignancies has led to an increase in the number of cancer survivors who are at risk of developing cardiotoxicity and heart failure. Cardiac dysfunction in these patients can occur asymptomatically, and the diagnosis in a symptomatic phase is associated with reduced treatment response and worse prognosis. For this reason, it is essential to establish protocols to follow up on these patients and identify those at risk of cardiotoxicity in order to start early and effective therapies. This review aims to summarize the latest findings in the diagnosis and treatment of cancer therapy-related cardiac disease in long-term survivors of childhood cancer, with a focus on heart failure.

A series of 3-cyano-2(1 H )-pyridones 4a-c were efficiently synthesized using an expeditious microwave-assisted multicomponent approach. Single-crystal XRD analysis revealed the presence of six independent molecules in the asymmetric unit cell for all compounds, with the crystal packing stabilized by a network of cyclic dimers formed by N-H⋯O[double bond, length as m-dash]C and C-H⋯O[double bond, length as m-dash]C intermolecular interactions. Additional supramolecular interactions, including C-H⋯π, C-N⋯π, and π⋯π, and C-H⋯X (for halogenated derivatives, i.e. , 4b and 4c), appear crucial for crystal stabilization. Density Functional Theory (DFT) calculations were employed to understand the electronic structures and potential binding affinities. Comprehensive spectroscopic characterization by FT-IR, UV-Vis, NMR, and HMRS techniques confirmed the structures of all synthesized compounds. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed to evaluate the thermal stability of these compounds. The in vitro anticancer activity was evaluated against a panel of 60 human cancer cell lines, demonstrating promising activity against non-small-cell lung and breast cancer cell lines. Notably, compounds 4a and 4c exhibited the highest anticancer activity against the HOP-92 and MCF7 cell lines, with growth inhibition percentages (GI%) of 54.35 and 40.25, respectively., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: To determine the factors influencing the likelihood of biochemical pregnancy loss (BPL) after transfer of a euploid embryo from preimplantation genetic testing for aneuploidy (PGT-A) cycles., Methods: The study employed an observational, retrospective cohort design, encompassing 6020 embryos from 2879 PGT-A cycles conducted between February 2013 and September 2021. Trophectoderm biopsies in day 5 (D5) or day 6 (D6) blastocysts were analyzed by next generation sequencing (NGS). Only single embryo transfers (SET) were considered, totaling 1161 transfers. Of these, 49.9% resulted in positive pregnancy tests, with 18.3% experiencing BPL. To establish a predictive model for BPL, both classical statistical methods and five different supervised classification machine learning algorithms were used. A total of forty-seven factors were incorporated as predictor variables in the machine learning models., Results: Throughout the optimization process for each model, various performance metrics were computed. Random Forest model emerged as the best model, boasting the highest area under the ROC curve (AUC) value of 0.913, alongside an accuracy of 0.830, positive predictive value of 0.857, and negative predictive value of 0.807. For the selected model, SHAP (SHapley Additive exPlanations) values were determined for each of the variables to establish which had the best predictive ability. Notably, variables pertaining to embryo biopsy demonstrated the greatest predictive capacity, followed by factors associated with ovarian stimulation (COS), maternal age, and paternal age., Conclusions: The Random Forest model had a higher predictive power for identifying BPL occurrences in PGT-A cycles. Specifically, variables associated with the embryo biopsy procedure (biopsy day, number of biopsied embryos, and number of biopsied cells) and ovarian stimulation (number of oocytes retrieved and duration of stimulation), exhibited the strongest predictive power., (© 2024. The Author(s).)

Northern peatlands are important carbon pools; however, differences in the structure and function of microbiomes inhabiting contrasting geochemical zones within these peatlands have rarely been emphasized. Using 16S rRNA gene sequencing, metagenomic profiling, and detailed geochemical analyses, we investigated the taxonomic composition and genetic potential across various geochemical zones of a typical northern peatland profile in the Changbai Mountains region (Northeastern China). Specifically, we focused on elucidating the turnover of organic carbon, sulfur (S), nitrogen (N), and methane (CH 4 ). Three geochemical zones were identified and characterized according to porewater and solid-phase analyses: the redox interface (<10 cm), shallow peat (10-100 cm), and deep peat (>100 cm). The redox interface and upper shallow peat demonstrated a high availability of labile carbon, which decreased toward deeper peat. In deep peat, anaerobic respiration and methanogenesis were likely constrained by thermodynamics, rather than solely driven by available carbon, as the acetate concentrations reached 90 μmol·L -1 . Both the microbial community composition and metabolic potentials were significantly different (p < 0.05) among the redox interface, shallow peat, and deep peat. The redox interface demonstrated a close interaction between N, S, and CH 4 cycling, mainly driven by Thermodesulfovibrionia, Bradyrhizobium, and Syntrophorhabdia metagenome-assembled genomes (MAGs). The archaeal Bathyarchaeia were indicated to play a significant role in the organic carbon, N, and S cycling in shallow peat. Although constrained by anaerobic respiration and methanogenesis, deep peat exhibited a higher metabolic potential for organic carbon degradation, primarily mediated by Acidobacteriota. In terms of CH 4 turnover, subsurface peat (10-20 cm) was a CH 4 production hotspot, with a net turnover rate of ∼2.9 nmol·cm -3 ·d -1 , while the acetoclastic, hydrogenotrophic, and methylotrophic methanogenic pathways all potentially contributed to CH 4 production. The results of this study improve our understanding of biogeochemical cycles and CH 4 turnover along peatland profiles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite the limited applications and scarcity of commercial examples of imidazo[1,2- a ]pyrimidines, their exceptional properties hold great potential, representing a significant challenge in discovering more critical applications. Herein, we present a microwave-assisted approach for preparing 2-arylimidazo[1,2- a ]pyrimidin-5(8 H )-ones and their alkylation and bromination products using easily accessible and inexpensive reagents, thus offering a promising avenue for further search. Notably, the photophysical properties of an N -alkyl derivative were investigated, and the results highlight the high potential of these compounds as modular fluorophores. All the products were obtained with high yields using highly efficient protocols, and the regioselectivity of the reactions was determined on the basis of NMR measurements and X-ray diffraction analysis., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Objective: Women undergoing IVF who have had a previous c-section (CS) have a lower live birth rate than those with a previous vaginal delivery. However, the precise underlying mechanisms need clarification. Does a previous CS affect the pattern of uterine contractility?., Methods: Prospective evaluation in patients undergoing frozen blastocyst embryo transfer in medicated endometrial preparation cycles. Twenty patients were included in groups: A/nulliparous. B/previous vaginal delivery. C/ previous CS without a niche, whereas fifteen patients were recruited in group D (CS and a niche). Patients employed estradiol compounds and 800 mg vaginal progesterone. A 3D-scan was performed the transfer-day where uterine contractility/minute was recorded., Results: Baseline characteristics (age, BMI, smoking, endometrial thickness) were similar. Mean frequency of uterine contractions/minute was similar between groups (1.15, 1.01, 0.92, and 1.21 for groups A, B, C, and D, respectively). There was a slight increase in the number of contractions in patients with a sonographic niche versus controls, not reaching statistical significance (p=0.48). No differences were observed when comparing patients with a previous C-section (regardless of the presence of a niche) to those without a C-section, either nulliparous (p=0.78) or with a previous vaginal delivery (p=0.80). The frequency of uterine contractions was similar between patients who achieved a clinical pregnancy and those who did not (1.19 vs. 1.02 UC/min, p=0.219, respectively)., Conclusions: Our study found no significant difference in the frequency of uterine contractility between patients with or without a previous C-section or sonographic diagnosed niche. Further investigation is necessary to understand the physiological mechanisms affecting implantation in patients with isthmocele.

Herein, a Cs 2 CO 3 -promoted N-alkylation of 3-cyano-2(1H)-pyridones containing alkyl groups with diverse alkyl halides to synthesize N-alkyl-2-pyridones over O-alkylpyridines is reported. The use of alkyl dihalides resulted in complex mixtures of N- and O-alkylated products. The primary factor influencing regioselectivity in these reactions is the electronic effects of substituents on the 2(1H)-pyridone ring, as evidenced by the preferential formation of O-alkylpyridines upon the introduction of aryl groups. Remarkably, we efficiently employed CuAAC and Ti(Oi-Pr) 4 -catalyzed amidation reactions to functionalize N-alkyl-2-pyridones containing propargyl and ester groups, leading to the synthesis of 1,2,3-triazoles and amides, respectively. Moreover, O-alkylpyridines 10 b and 10 d displayed remarkable selectivity toward the A-498 renal cancer cell line with growth inhibition percentages (%GI) of 54.75 and 67.64, respectively. The binding modes of compounds 10 b and 10 d to the PIM-1 kinase enzyme were determined through molecular docking studies., (© 2024 Wiley-VCH GmbH.)

Research Question: Conflicting data exists regarding whether a younger age of donors has a negative influence on the outcomes of oocyte donation cycles. Is there any correlation between a younger age of donors and the rate of embryonic aneuploidy in oocyte donation cycles?, Design: Retrospective study including 515 oocyte donation cycles carried out between February 2017 and November 2022. Comprehensive chromosomal screening was performed on 1831 blastocysts. 1793 had a result which were categorised into groups based on the age of the donor: 18-22 (n = 415), 23-25 (n = 600), 26-30 (n = 488), and 31-35 years (n = 290). The analysis aimed to determine the percentage of biopsy samples that were euploid and the number that were aneuploid, relative to the age group of the oocyte donor. Additionally, linear regression was employed to examine the relationship between age and the proportion of aneuploid embryos, while controlling for relevant variables., Results: Aneuploidy increased predictably with donor age: 18-22 years: 27.5 %; 23-25 years: 31.2 %; 26-30 years: 31.8 %; and 31-35 years: 38.6 %. In the donor group aged 31-35 years, a higher percentage of aneuploid embryos was observed compared to younger donors in univariate analysis (OR: 1.66, 95 % CI: 1.21-2.29, p = 0.002) and multivariate logistic analysis (OR: 2.65, 95 % CI: 1.67-4.23, p < 0.001). The rates of embryonic mosaicism revealed no significant differences., Conclusion: The lowest risk of embryonic aneuploidy was found among donors aged <22 years. Conversely, an elevated prevalence was evident within the donor group aged 31-35 years, in contrast to the younger cohorts. The incidence of mosaic embryos remained consistent across all age groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

During the COVID-19 pandemic, a considerable proportion of patients developed a severe condition that included respiratory failure, shock, or multiple organ dysfunction. Acute Kidney Injury (AKI) has been recognized as a possible cause of severe COVID-19 development. Given this, this study investigates the occurrence and consequences of AKI in Mexican patients to contribute to better knowledge and management of this problem. Methods : Using a retrospective observational cohort methodology, we investigated 313 cases from a cohort of 1019 patients diagnosed with COVID-19 at the IMSS Zacatecas General Hospital of Zone No. 1 in 2020. The prevalence of AKI was determined using the AKIN criteria based on serum creatinine levels and a detailed review of demographic characteristics, medical history, comorbidities, and clinical development. Results : The data showed a 25.30% prevalence of AKI among patients infected with severe COVID-19. Remarkably, these patients with AKI exhibited an advanced age (>65 years), arterial hypertension, a higher number of white blood cells during admission and the hospital stay, and elevated levels of C-reactive protein, serum creatinine, and blood urea nitrogen (BUN). Clinically, patients with AKI had signs of prostration, pneumonia, and the requirement for ventilatory assistance when compared to those without AKI. Finally, those diagnosed with AKI and COVID-19 had a 74% death rate. Relative risk analyses indicated that age (>65 years), arterial hypertension, high creatinine levels, endotracheal intubation, and pneumonia are associated with the development of AKI. On the other hand, among the protective factors against AKI, high hemoglobin levels and the consumption of statins during COVID-19 were found. Conclusions : The findings of this study underscore the significance of promptly identifying and effectively managing AKI to potentially alleviate the negative consequences of this complication within the Mexican population during COVID-19.

Purpose: Understanding early vascular ageing has become crucial for preventing adverse cardiovascular events. To this respect, recent AI-based risk clustering models offer early detection strategies focused on healthy populations, yet their complexity limits clinical use. This work introduces a novel recommendation system embedded in a web app to assess and mitigate early vascular ageing risk, leading patients towards improved cardiovascular health., Methods: This system employs a methodology that calculates distances within multidimensional spaces and integrates cost functions to obtain personalized optimisation of recommendations. It also incorporates a classification system for determining the intensity levels of the clinical interventions., Results: The recommendation system showed high efficiency in identifying and visualizing individuals at high risk of early vascular ageing among healthy patients. Additionally, the system corroborated its consistency and reliability in generating personalized recommendations among different levels of granularity, emphasizing its focus on moderate or low-intensity recommendations, which could improve patient adherence to the intervention., Conclusion: This tool might significantly aid healthcare professionals in their daily analysis, improving the prevention and management of cardiovascular diseases., Competing Interests: Conflict of interestThe authors declares no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The COVID-19 pandemic has highlighted our reliance on biocides, the increasing prevalence of resistance to biocides is a risk to public health. Bacterial exposure to the biocide, benzalkonium chloride (BAC), resulted in a unique transcriptomic profile, characterised by both a short and long-term response. Differential gene expression was observed in four main areas: motility, membrane composition, proteostasis, and the stress response. A metabolism shift to protect the proteome and the stress response were prioritised suggesting these are main resistance mechanisms. Whereas "well-established" mechanisms, such as biofilm formation, were not found to be differentially expressed after exposure to BAC., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: This study begins with the analysis of the current management models and their degree of effectiveness in municipal administration. Its aim is to design an administrative management model that enables effective administration in the District Municipality of Nueva Cajamarca, Peru, based on the theory of intelligent organizations., Method: The research type employed in this study is diagnostic-propositional, utilizing both deductive and inductive methods, in alignment with a mixed-method approach and a non-experimental nature of the study. Data was collected from three distinct populations, including the 189 municipal employees engaged in administrative roles, who were subjected to a 50-question survey. This survey aimed to assess their perceptions regarding the current management model and its relationship with administrative effectiveness. Additionally, interviews were conducted with three experts to gain deeper insights into the behavior of the variables under investigation., Results: Finally, documentary information about the management models currently in use was collected. This facilitated the triangulation of data collection, processing, analysis, and inferences from three sources of information. The results reveal a positive, direct, and significant correlation between the management model and administrative effectiveness. It becomes evident that the current management model is deficient, resulting in a low level of administrative effectiveness., Conclusion: The management model based on the theory of intelligent organizations was validated using a rubric by experts in effective management. The main pillars of this model include transformational leadership, structural change, and cultural change., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Tarrillo Carrasco JE et al.)

Objective: To explore the use of weekly continuous dosing of corifollitropin α in DuoStim cycles., Design: Pilot-matched case-control study., Setting: Private fertility center., Patients: Cases were defined as DuoStim cycles performed from November 2022 to May 2023 receiving weekly continuous dosing of corifollitropin α (n = 15). Controls were chosen from a database comprising DuoStim cycles conducted at our institution during the years 2021/2022. Matching was done on a 1-to-1 basis, based on antimüllerian hormone values (±0.4 pmol/L) and age (n = 15)., Interventions: Injections of corifollitropin α once every 8 days, along with uninterrupted oral administration of micronized progesterone 200 mg/d (for luteinizing hormone surge prevention) throughout the follicular and luteal phases for ovarian stimulation. Oocyte retrieval., Main Outcome Measures: Total number of cumulus-oocyte complexes and metaphase II oocytes obtained in follicular + luteal phase stimulation. Secondary outcomes evaluated fertilization rates, number of blastocysts, days of stimulation, number of injectables required, and gonadotropin cost., Results: The study group achieved similar total oocyte and MII yield vs. daily follicle-stimulating hormone protocol (13.3 ± 6.9 vs. 11.8 ± 6.1 and 10.4 ± 6.3 vs. 9.2 ± 4.6, respectively). All secondary outcomes showed no significant differences. The study group experienced a significant reduction of injections to complete a DuoStim cycle (4.5 ± 1.4 vs. 35.2 ± 12.2; mean deviation -30.7; 95% confidence interval, -37.5- to -23.9)]., Conclusions: Corifollitropin α on a weekly basis throughout a DuoStim cycle yields an equivalent number of oocytes as standard daily follicle-stimulating hormone administration while drastically reducing the number of required injections., Trial Registration Number: NCT05815719. EudraCT: 2022-003177-32., Competing Interests: J.C.C. has nothing to declare. A.F. has nothing to declare. J.A.O. has nothing to declare. E.A. has nothing to declare. A.B. has nothing to declare. R.B. has nothing to declare., (© 2024 The Authors.)

Introduction: Progesterone-primed cycles effectively suppress the pituitary LH surge during ovarian stimulation in oocyte donors and in the infertile population. Particularly in oocyte donors, the use of synthetic progesterone (progestins) has been explored in prospective clinical trials, showing mixed results. This trial was designed to determine whether the use of micronized natural progesterone is as effective as the GnRH-antagonist protocol in terms of the number of mature oocytes (MII) retrieved in oocyte donation cycles as a primary outcome, and it also aims to explore the corresponding results in recipients as a secondary outcome., Methods: We propose a prospective, open-label, non-inferiority clinical trial to compare a novel approach for oocyte donors with a control group, which follows the standard ovarian stimulation protocol used in our institution. A total of 150 donors (75 in each group) will be recruited and randomized using a computer algorithm. After obtaining informed consent, participants will be randomly assigned to one of two ovarian stimulation protocols: either the standard GnRH antagonist or the oral micronized natural progesterone protocol. Both groups will receive recombinant gonadotropins tailored to their antral follicle count and prior donation experiences, if any. The primary outcome is the number of mature metaphase II (MII) oocytes. Secondary measures include treatment duration, pregnancy outcomes in recipients, as well as the economic cost per MII oocyte obtained in each treatment regimen. Analyses for the primary outcome will be conducted in both the intention-to-treat (ITT) and per-protocol (PP) populations. Each donor can participate only once during the recruitment period. The estimated duration of the study is six months for the primary outcome and 15 months for the secondary outcomes., Discussion: The outcomes of this trial have the potential to inform evidence-based adjustments in the management of ovarian stimulation protocols for oocyte donors., Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT05954962., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martínez-Moya, Guerrero, Girela, Pitas, Bernabeu, Bernabeu and Castillo.)

CD4 + forkhead box P3 (FOXP3) + regulatory T cells (Tregs) are essential in maintaining immune tolerance and suppressing excessive immune responses. Tregs also contribute to tissue repair processes distinct from their roles in immune suppression. For these reasons, Tregs are candidates for targeted therapies for inflammatory and autoimmune diseases, and in diseases where tissue damage occurs. MT-2 cells, an immortalized Treg-like cell line, offer a model to study Treg biology and their therapeutic potential. In the present study, we use clustered regularly interspaced palindromic repeats (CRISPR)-mediated knockdown of FOXP3 in MT-2 cells to understand the transcriptional and functional changes that occur when FOXP3 is lost and to compare MT-2 cells with primary human Tregs. We demonstrate that loss of FOXP3 affects the transcriptome of MT-2 cells and that FOXP3's potential downstream targets include a wide range of transcripts that participate in the cell cycle, promote growth and contribute to inflammatory processes, but do not wholly simulate previously reported human primary Treg transcriptional changes in the absence of FOXP3. We also demonstrate that FOXP3 regulates cell cycling and proliferation, expression of molecules crucial to Treg function and MT-2 cell-suppressive activities. Thus, MT-2 cells offer opportunities to address regulatory T-cell functions in vitro., (© 2024 the Australian and New Zealand Society for Immunology, Inc.)

Introduction: Neurocysticercosis (NCC), a possible cause of epilepsy with limited epidemiological data in the Dominican Republic, is endemic in four provinces in the country's south-western region. This study aimed to determine the association between NCC and epilepsy among people living in these endemic regions, and to obtain preliminary data on the prevalence of NCC in these provinces., Patients and Methods: A case-control design was used, consisting of 111 patients with epilepsy with unknown causes, and 60 controls without epilepsy or NCC. The diagnosis of NCC was based on computed tomography and magnetic resonance imaging of the skull, as well as Western immunoblotting for serum antibodies using Taenia solium, following the criteria of Del Brutto et al. RESULTS. NCC was found in 27% of the epileptic patients (n = 30/111) and in 5% of the controls (n = 3/60); the probability of the epileptic patients having NCC was seven times higher than the controls (odds ratio = 7.04, 95% confidence interval: 2.04-24.18; p < 0.001). The participants' sociodemographic characteristics, including their age, sex, level of education, occupation, and province of residence presented no statistical significance in terms of their association with NCC., Conclusions: This study suggests that NCC is strongly associated with epilepsy in the south-western region of the Dominican Republic, and highlights the need for public health measures to improve the prevention, diagnosis and treatment of both diseases.

Introduction and Objectives: Survivors of childhood cancer might be at increased risk of diastolic dysfunction at follow-up due to exposure to cardiotoxic treatment. Although assessment of diastolic function is challenging in this relatively young population, left atrial strain might provide a novel insight in this evaluation. Our aim was to examine diastolic function in a cohort of long-term survivors of childhood acute lymphoblastic leukemia by using left atrial strain and conventional echocardiographic parameters., Methods: Long-term survivors who were diagnosed at a single center between 1985 and 2015 and a control group of healthy siblings were recruited. Conventional diastolic function parameters and atrial strain were compared, and the latter was measured during the 3 atrial phases: reservoir (PALS), conduit (LACS) and contraction (PACS). Inverse probability of treatment weighting was used to account for differences between the groups., Results: We analyzed 90 survivors (age, 24.6±9.7 years, time since diagnosis 18 [11-26] years) and 58 controls. PALS and LACS were significantly reduced compared with the control group: 46.4±11.2 vs 52.1±11.7; P=.003 and 32.5±8.8 vs 38.2±9.3; P=.003, respectively. Conventional diastolic parameters and PACS were similar between the groups. The reductions in PALS and LACS were associated with exposure to cardiotoxic treatment in age- and sex-adjusted analysis (≥ moderate risk, low risk, controls): 45.4±10.5, 49.5±12.9, 52.1±11.7; P adj =.003, and 31.7±9.0, 35.2±7.5, 38.2±9.3; P adj =.001, respectively., Conclusions: Long-term childhood leukemia survivors showed a subtle impairment of diastolic function that was detected with atrial strain but not with conventional measurements. This impairment was more pronounced in those with higher exposure to cardiotoxic treatment., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Research Question: Do live birth rates differ between recipients matched with donors using conventional ovarian stimulation compared with those using random-start protocols?, Design: Retrospective analysis of 891 ovarian stimulations in egg donors (January-December 2018) and clinical outcomes in matched recipients (n = 935). Donors commenced ovarian stimulation on day 1-3 of the menstrual cycle (n = 223) or in the mid/late-follicular (n = 388) or luteal phase (n = 280) under a conventional antagonist protocol. Live birth rate of matched recipients was the main outcome., Results: Duration of stimulation and total gonadotrophin dose were comparable between conventional versus random-start groups. The number of collected eggs were similar (17.6 ± 8.8 versus 17.2 ± 8.5, P = 0.6, respectively). Sub-group analysis showed that stimulation length (10.2 ± 1.8 versus 9.8 ± 1.7 versus 10.4 ± 1.7, P < 0.001) and gonadotrophin consumption (2041.5 ± 645.3 versus 2003.2 ± 647.3 versus 2158.2 ± 685.7 IU, P = 0.01) differed significantly between the conventional, mid/late follicular and luteal phase groups, respectively. In matched recipients receiving fresh oocytes and undergoing fresh embryo transfer, the biochemical pregnancy (63.8% and 63.3%; P = 0.9), clinical pregnancy (54.6% and 56.1%; P = 0.8) and live birth rates (47.7% and 46.6%; P = 0.7) per embryo-transfer were similar between conventional versus random groups. Similar results were obtained in recipients receiving vitrified eggs. Euploidy rate was also comparable., Conclusions: No notable variations were found in clinical outcomes using oocytes obtained from random-start protocols and those proceeding from conventional ovarian stimulation in oocyte donation treatments. Luteal-phase stimulation seems to require longer stimulation and higher FSH consumption. Random-start stimulation strategy does not impair the potential of the oocyte yield or clinical outcomes in oocyte donation cycles., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: Matching into orthopaedic residency has become difficult, and the US Medical Licensing Examination Step 1 transition to pass/fail scoring has complicated the process. Advisors' ability to mentor students has decreased, and program directors may rely on Step 2 Clinical Knowledge (CK) scores in selecting which candidates to interview. This study aims to offer a method to predict Step 2 CK outcomes based on preadmission and preclinical performance., Methods: The study investigated 486 students from a US medical school who enrolled in 2017 and 2018. Data on demographics, preadmission, and preclinical performance were collected. Before model creation, it was found that sex, Medical College Admission Test scores, Comprehensive Basic Science Examination performance, and preclinical curriculum performance produced optimal models. Multivariate ordinal logistic regression models were built to predict probabilities of four outcome levels of Step 2 CK: <235, 235 to 249, 250 to 265, and >265. Finally, nomograms were created to visualize probability calculations., Results: Each model's odds ratios revealed that female sex, higher MCAT scores, and better Comprehensive Basic Science Examination and preclinical performance were associated with an increased likelihood of being in higher Step 2 CK scoring groups. Preclinical performance had a profound effect, especially for those in the top 1/3. Models were successful in assigning higher probabilities to students in higher Step 2 CK scoring groups in more than 80% of instances. Nomograms presented provide examples of how to apply these models to an individual student., Discussion: This study presents a novel method for predicting probabilities of Step 2 CK outcomes that can be used to mentor students at a time point when Step 1 previously filled this role. It may assist in identifying orthopaedic hopefuls at risk of performing poorly on Step 2 CK and can foster the development of individualized guidance and mitigation strategies., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

The new title pyrrole-pyrazole derivative, C 16 H 16 BrN 3 , was synthesized through a citric acid-catalyzed Paal-Knorr reaction between acetonylacetone and 1-(4-bromophenyl)-3-methyl-1H-pyrazol-5-amine under mild reaction conditions. This synthetic protocol is noteworthy for its utilization of stoichiometric amounts of the reactants, an ecofriendly solvent and a cost-effective, non-toxic and biodegradable organocatalyst. A comprehensive understanding of the molecular structure was gained through spectroscopic, thermal and X-ray crystallographic analyses. The crystal structure is characterized by weak interactions, where only C-H...π connections contribute to the hydrogen-bond contacts. The supramolecular assembly is controlled by dispersion forces. However, the energy frameworks demonstrate that these forces act in three dimensions, providing enough stability, as observed in TGA-DSC (thermogravimetric analysis-differential scanning calorimetry) studies.

Background: The first year of dialysis is critical given the significant risk for complications following dialysis initiation. We analysed complications during the first year among incident peritoneal dialysis (PD) patients., Methods: This retrospective cohort study comprised adult kidney failure patients starting PD in Baxter Renal Care Services in Colombia, receiving their first PD catheter between 1 January 2017 and 31 December 2020 and were followed up for up to 1 year. We analysed incidence, causes and factors associated with complications using logistic regression and transfer to haemodialysis (HD) using the Fine-Gray regression model., Results: Among 4743 patients receiving their first PD catheter: 4628 (97.6%) of catheter implantations were successful; 377 (7.9%) patients experienced early complications. The incidence rate of complications during the year was 0.51 events per patient-year (95% CI: 0.48-0.54). Age, obesity and urgent start were associated with higher probability of complications after catheter implantation. The cumulative incidence of transfer to HD within 1 year of PD initiation was 10.1% [95% CI: 9.2-11.1%]. The hazard function for transfer to HD showed an accelerating pattern during the first month followed by progressive decrease during the first year., Conclusions: In this large population of incident PD patients, there is a high primary catheter placement success rate. Urgent start, age ≥65 years, obesity, centre size ≥150 PD patients and diabetes were risk factors associated with early complications. The follow-up of the cohort from day 1 of PD treatment showed that the risk for transfer to HD was higher during the first month., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ASR is full-time employee of Baxter Healthcare Corporation, Deerfield, IL, USA; JIV and LEN are full-time employee of Baxter Renal Care Services Bucaramanga, Colombia; SP is an employee of Department of Statistics, Science Faculty, National University of Colombia, Bogota DC, Colombia, and he has received honorarium for consultancy and statistical analysis from Baxter Renal Care Services-Colombia; KA, AA, YA and JCC are full-time employee of Baxter Renal Care Services, Bogota DC, Colombia; BL is an employee of Division of Baxter Novum and Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; MS is full-time employee of Baxter Renal Care Services-Latin America, Bogota DC, Colombia and PR is an employee of Baxter Healthcare Corporation, Zürich, Switzerland.

The conversion of residual biomass from fruit seeds into biochar can be achieved using MgCl 2 as an activating agent and calcining at 700 °C. The resulting MgO-biochars were employed in the aldol condensation reaction between furfural and acetone. This reaction is essential as the first step in the obtention of biofuels derived from biomass. The biochars were characterized through various physicochemical techniques, revealing that the presence of MgO nanoparticles deposited on the carbon surface modifies the structural and acidic-basic properties of the carbonaceous materials with a graphitic structure. The biochar with a surface content of MgO of 0.34 % w/w enables the achievement of 100 % of selectivity towards 4-(2-furanyl)-3-buten-2-one (I) with quantitative conversions under optimized conditions. This property highlights the potential of using this type of biochar, commonly used for CO 2 capture, as a versatile acidic-basic catalyst, thereby introducing a novel approach to sustainable chemistry., (© 2023 Wiley-VCH GmbH.)

There are limited data regarding right ventricle (RV) impairment in long-term survivors of childhood acute lymphoblastic leukemia (CLS). The aim of this study was to assess RV function in these patients using echocardiographic conventional measurements and automated RV strain. Echocardiographic recordings of 90 CLS and 58 healthy siblings from the CTOXALL cohort were analyzed. For group comparisons, inverse probability weighting was used to reduce confounding. The CLS group (24.6 ± 9.7 years, 37.8% women) underwent an echocardiographic evaluation 18 (11-26) years after the diagnosis. RV systolic dysfunction was found in 16.7% of CLS individuals using RV free-wall strain (RVFWS) compared to 2.2 to 4.4% with conventional measurements. RV systolic function measurements were lower in the CLS than in the control group: TAPSE (23.3 ± 4.0 vs. 25.2 ± 3.4, p = 0.004) and RVFWS (24.9 ± 4.6 vs. 26.8 ± 4.7, p = 0.032). Modifiable cardiovascular risk factors such as obesity ( p = 0.022) and smoking ( p = 0.028) were independently associated with reduced RVFWS. In conclusion, RV systolic function impairment was frequent in long-term survivors of childhood leukemia, underscoring the importance of RV assessment, including RVFWS, in the cardiac surveillance of these patients.

Chronic wounds are a latent health problem worldwide, due to high incidence of diseases such as diabetes and Hansen. Typically, wound evolution is tracked by medical staff through visual inspection, which becomes problematic for patients in rural areas with poor transportation and medical infrastructure. Alternatively, the design of software platforms for medical imaging applications has been increasingly prioritized. This work presents a framework for chronic wound tracking based on deep learning, which works on RGB images captured with smartphones, avoiding bulky and complicated acquisition setups. The framework integrates mainstream algorithms for medical image processing, including wound detection, segmentation, as well as quantitative analysis of area and perimeter. Additionally, a new chronic wounds dataset from leprosy patients is provided to the scientific community. Conducted experiments demonstrate the validity and accuracy of the proposed framework, with up to 84.5% in precision., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Does the use of 400mg pessaries of micronized progesterone provide comparable results as pessaries of 200mg x2, in terms of progesterone levels in hormonal replacement cycles for embryo transfer?., Methods: Retrospective cohort study based on 299 embryo transfer treatments under artificial endometrial preparation carried out at Instituto Bernabeu. 131 patients received 1 pessary of 400 mg b.i.d. (group A) and 168 received 2 pessaries of 200 mg b.i.d. (group B)., Results: Mean serum progesterone levels were similar between groups (A: 13.64±4.47ng/mL vs. B: 13.88±7.17ng/mL). There were no differences in suboptimal progesterone levels between groups (A: 11.5% vs. B: 16.8%). In terms of patients receiving additional progesterone supplementation, there were no differences between groups (A: 26% vs. B: 35.3%.). No differences between groups were observed in clinical outcomes: pregnancy rate (PR) (A: 55% vs. B: 54.8%), biochemical pregnancy loss rate (BPLR) (A: 13.4% vs. B: 17.6%), miscarriage rate (MR) (A: 17.9% vs. B: 19.8%) and ongoing pregnancy rate (OPR) (A: 36.5% vs. B: 34.1%)., Conclusions: One progesterone pessary of 400mg (Cyclogest®) twice daily appears to be non-inferior to the use of two-200mg pessaries twice daily in terms of progesterone levels in HRT cycles.

Objective: Is self-detection of the endogenous LH surge using a urine testing a reliable method to confirm a successful gonadotropin-releasing hormone agonist (GnRHa) trigger in IVF cycles?, Methods: Prospective observational study including a total of 103 oocyte donation cycles between November 2019 and January 2020. Urine LH testing (Akralab SL, Spain, cut-of value 30 mIU/mL) was performed at home in samples from the first micturition in the morning after the GnRHa trigger and a picture of the result was sent to the nurse coordinator; this information was concealed and only disclosed after oocyte aspiration., Results: From the total group, two cycles were excluded. A total of 101 oocyte donors performed the LH urine testing, all proceeded to oocyte aspiration and were included in final analysis. A total of 85 (84.2%) had a positive LH test and an uneventful oocyte retrieval with good retrieval rates (false positive rate: 0%). A total of 16 had a negative LH test (15.8%) and had a good oocyte retrieval rates (false negative rate: 15.8%). There were no cases of empty follicle syndrome., Conclusions: Due to a high false negative rate, self-testing of endogenous LH release using a LH urine test when performed approximately 12-hours after triggering does not seem to be a reliable method to predict a suboptimal response to gonadotropin-releasing hormone.

Background: Morbidity and mortality in lung transplant recipients are often triggered by recurrent aspiration events, potentiated by oesophageal and gastric disorders. Previous small studies have shown conflicting associations between oesophageal function and the development of chronic lung allograft dysfunction (CLAD). Herein, we sought to investigate the relationship between oesophageal motility disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients., Methods: All lung transplant recipients at the Toronto Lung Transplant Program from 2012 to 2018 with available oesophageal manometry testing within the first 7 months post-transplant were included in this study. Patients were categorised according to the Chicago Classification of oesophageal disorders (v3.0). Associations between oesophageal motility disorders with the development of CLAD and allograft failure (defined as death or re-transplantation) were assessed., Results: Of 487 patients, 57 (12%) had oesophagogastric junction outflow obstruction (OGJOO) and 47 (10%) had a disorder of peristalsis (eight major, 39 minor). In a multivariable analysis, OGJOO was associated with an increased risk of CLAD (HR 1.71, 95% CI 1.15-2.55, p=0.008) and allograft failure (HR 1.69, 95% CI 1.13-2.53, p=0.01). Major disorders of peristalsis were associated with an increased risk of CLAD (HR 1.55, 95% CI 1.01-2.37, p=0.04) and allograft failure (HR 3.33, 95% CI 1.53-7.25, p=0.002). Minor disorders of peristalsis were not significantly associated with CLAD or allograft failure., Conclusion: Lung transplant recipients with oesophageal stasis characterised by OGJOO or major disorders of peristalsis were at an increased risk of adverse long-term outcomes. These findings will help with risk stratification of lung transplant recipients and personalisation of treatment for aspiration prevention., Competing Interests: Conflicts of interest: P. Riddell is an associate editor of this journal. L. Liu has received honoraria from AbbVie, Medtronic, Lupin, Knight and Bausch Health as a speaker and consultant. S. Keshavjee is a corporate board member for United Therapeutics and current patent holder with SQI Diagnostics. T. Martinu received a research grant from Sanofi Inc. and research material from APCBio Innovations Inc., and collaborates (with no fees) with Trove Therapeutics. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

The importance of the benzo[ b ]furan motif becomes evident in the remarkable results of numerous biological investigations, establishing its potential as a robust therapeutic option. This review presents an overview of the synthesis of and exhaustive biological studies conducted on benzo[ b ]furan derivatives from 2011 to 2022, accentuating their exceptional promise as anticancer, antibacterial, and antifungal agents. Initially, the discussion focuses on chemical synthesis, molecular docking simulations, and both in vitro and in vivo studies. Additionally, we provide an analysis of the intricate interplay between structure and activity, thereby facilitating comparisons and profoundly emphasizing the applications of the benzo[ b ]furan motif within the realms of drug discovery and medicinal chemistry.