Specific Rosetta-based protein-peptide prediction protocol allows the design of novel cholinesterase inhibitor peptides.

The search for novel cholinesterase inhibitors is essential for advancing treatments for neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we employed the Rosetta pepspec module, originally developed for designing peptides targeting protein-protein interactions, to design de novo peptides targeting the peripheral aromatic site (PAS) of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). A total of nine peptides were designed for human AChE (hAChE), T.

Development and Characterization of Trihexyphenidyl Orodispersible Minitablets: A Challenge to Fill the Therapeutic Gap in Neuropediatrics.

Trihexyphenidyl (THP) has been widely used for over three decades as pediatric pharmacotherapy in patients affected by segmental and generalized dystonia. In order to achieve effective and safe pharmacotherapy for this population, new formulations are needed. The aim of this work is the development of trihexyphenidyl orodispersible minitablets (ODMTs) for pediatric use.

Herbicidal Formulations with Plant-Based Compounds to Control , and Weeds.

Numerous studies have shown the potential effect of bioactive agents against weeds. In this study, we developed two binary formulations with nonanoic acid, citral, or thymoquinone as herbicides and evaluated their physicochemical properties. The presence of the bioactive compounds in the formulations was confirmed through FTIR spectroscopy.

Jurassic Osmundaceous Landscapes in Patagonia: Exploring the Concept of Ecological Stasis in the Deseado Massif, Argentina.

Herein, we report the presence of a plant paleocommunity, dominated by ferns of the family Osmundaceae, structurally preserved from the only known Mesozoic, fossiliferous geothermal deposits, from the La Matilde Formation (Middle-Upper Jurassic) in the Deseado Massif of Southern Patagonia, Argentina. A total of 13 siliceous chert blocks sampled in an area of approximately 250 m, preserving a monotypic assemblage dominated by Osmundaceae embedded within its original swampy substrate, are documented. Additional Osmundaceae and fewer ferns and conifers are present in the stratigraphically continuous, adjacent chert levels.

Reproduction control in a feral feline population using an anti-GnRH vaccine.

This study aimed to evaluate the use of the Improvac® vaccine to avoid heat and pregnancies in queens and fertility in males during the breeding season. Twenty-eight intact animals were divided into treated males (G1, n = 7), treated females (G2, n = 18), and untreated males (G3, n = 3) that were untamed and could not be captured for immunization. In cats from the G1 group, the testicular volume (337.

[Utility of CT Cardiac Angiography in the Evaluation of Infective Endocarditis and Its Complications].

Infective endocarditis (IE) is an infection that affects the heart valves, endocardium, and great vessels. It has a mortality rate of approximately 30% per year, so early diagnosis is essential to reduce morbidity and mortality. Cardiac angio-CT triggered by electrocardiogram (ECG) has been considered in IE management guidelines in recent years, given its high spatial resolution, contributing to the diagnosis and evaluation of valvular complications (vegetations, perforations, dysfunctions), perivalvular (abscesses, pseudoaneurysms, prosthesis dehiscence, fistulas) and compromised coronary arteries (embolism), allowing early diagnosis and treatment.

Unveiling the Potential of Southern Elderberry (Sambucus australis): Characterization of Physicochemical Properties, Carbohydrates, Organic Acids and Biophenols.

Sambucus australis is a wild species with purple fruits like berries. It is native from South America and can be found in Argentina, Uruguay, Paraguay, Bolivia, and Brazil. A comprehensive characterization of S.

The Brussels consensus for non-invasive ICP monitoring when invasive systems are not available in the care of TBI patients (the B-ICONIC consensus, recommendations, and management algorithm).

Background: Invasive systems are commonly used for monitoring intracranial pressure (ICP) in traumatic brain injury (TBI) and are considered the gold standard. The availability of invasive ICP monitoring is heterogeneous, and in low- and middle-income settings, these systems are not routinely employed due to high cost or limited accessibility. The aim of this consensus was to develop recommendations to guide monitoring and ICP-driven therapies in TBI using non-invasive ICP (nICP) systems.

New formulation of ibuprofen-arginate reduces oxidative stress and prevents macrophage polarization toward M1 phenotype.

A hypertonic solution of Ibuprofen (Ibu) was designed to nebulize, associating a low concentration of Ibu with L-Arginine (AR), to increase solubility and serve as a nitric oxide donor. To provide preclinical research human bronchial epithelial cells derived from a cystic fibrosis patient homozygous for the ΔF508 CFTR mutation (CFBE41o-) and mouse RAW 264.7 macrophages were pre-treated with Ibu (10-100 μM), AR (20 and 200 μM), or the combination Ibu-AR (10-100 μM).

Stress responsiveness in a wild primate predicts survival across an extreme El Niño drought.

We know more about the costs of chronic stress than the benefits of the acute stress response-an adaptive response that buffers organisms from life-threatening challenges. As yet, no primate study has empirically identified how the stress response adaptively affects evolutionary fitness. Here, we take advantage of a natural experiment-an El Niño drought-that produced unprecedented mortality for wild white-faced capuchins.

A Continuum From Positive to Negative Interactions Drives Plant Species' Performance in a Diverse Community.

With many species interacting in nature, determining which interactions describe community dynamics is nontrivial. By applying a computational modeling approach to an extensive field survey, we assessed the importance of interactions from plants (both inter- and intra-specific), pollinators and insect herbivores on plant performance (i.e.

A multicenter study on enteral autonomy outcome of pediatric intestinal failure patients from a middle-income country.

Background & Aims: To identify predictors of enteral autonomy and survival in pediatric intestinal failure patients followed up at three pediatric intestinal rehabilitation centers from a middle-income country.

Methods: This retrospective multicenter cohort study evaluated patients with intestinal failure from three high-volume intestinal rehabilitation centers on long-term parenteral nutrition between 2014 and 2023. The primary outcome was status at the end of the follow-up: parenteral nutrition dependence, enteral autonomy, transplantation, or death.

Validation of an in house iELISA for serodiagnosis of caprine brucellosis and evaluation of the performance of a B. neotomae lysate for the detection of anti-smooth Brucella specific antibodies in ruminants.

Enzyme-linked immunosorbent assay (ELISA) is a widely used and effective tool for detection of anti-Brucella antibodies in serum, easy to perform with high sensitivity and specificity. In this study, we validated an in-house indirect ELISA using B. melitensis whole cell lysate as antigen (Bm-WCL iELISA) for the serodiagnosis of caprine brucellosis and evaluated the use of BSL-2 B.

Effect of increasing lipid levels on liver metabolism, intestinal morphology and production performance of discus fish (Symphysodon aequifasciatus).

The objective of this study was to evaluate the effects of three levels of lipids in the diet on growth, metabolism, and intestinal and hepatic histopathology in discus fish (Symphysodon aequifasciatus). Fish were stocked in quadruplicate in aquarium (50L) and were fed experimental diets containing three levels (3%, 10%, and 14%) of dietary lipids (LP). At the end of the trial, no significant differences in growth performance were observed.

Spatial occurrence of emerging contaminants in rivers and wastewater. Analysis of environmental and human risks.

This study assesses the occurrence of emerging contaminants (ECs) from agricultural and livestock production activities along the Salado River (Santa Fe province, Argentina). Of the 23 ECs studied, 8 were detected and quantified in river and wastewater samples, including ciprofloxacin, enrofloxacin, chlorpyrifos-methyl, albendazole, fenbendazole, levamisole, diazepam, and thiamethoxam. In river samples, the highest concentrations corresponded to ciprofloxacin, chlorpyrifos-methyl, and enrofloxacin.

Smoking Cessation Interventions in the Lung Cancer Screening Setting: A Randomized Clinical Trial.

Importance: The optimal configuration of a smoking cessation intervention in a lung cancer screening (LCS) setting has not yet been established.

Objective: To evaluate the efficacy of 3 tobacco treatment strategies of increasing integration and intensity in the LCS setting.

Design, Setting, And Participants: In this randomized clinical trial, LCS-eligible current smokers were randomized into 3 treatments: quitline (QL), QL plus (QL+), or integrated care (IC).

Novel Therapies to Reduce Rehospitalization Risk in Worsening Heart Failure: Systematic Review and Network Meta-Analysis.

Background: Worsening heart failure (WHF) challenges health care with frequent rehospitalizations and reduced quality of life for patients. Despite therapeutic advances, high rehospitalization risks highlight the urgent need for new treatments.

Objectives: This study evaluated the effectiveness of initiating novel therapies during hospitalization or vulnerable phase for WHF patients to reduce rehospitalization risks and determine the optimal treatment sequence.

Screening and Selection of Native Lactic Acid Bacteria Isolated from Chilean Grapes.

The aim of this study was investigating the biological diversity of lactic acid bacteria isolated from Chilean grapes and identifying potential candidates for use as malolactic fermentation starter cultures. The isolated bacteria underwent a comprehensive six-stage screening process, which was mutually exclusive except for the evaluation of tyramine production and citric acid intake. This process included morphological, metabolic, fermentation yield, and resistance tests to identify promising malolactic strains.

The role of the complement system in Shiga toxin-associated hemolytic uremic syndrome.

Background: This research explores complement activation products involvement and risk and protective polymorphisms in the complement alternative pathway genes in Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) pathogenesis.

Methods: We analyzed the levels of complement activation products, C3a, C5a and soluble C5b-9 (sC5b-9) and plasma concentrations of Factor H (FH) and FH-related protein 1 (FHR-1) in 44 patients with STEC-HUS, 12 children with STEC-positive diarrhea (STEC-D), and 72 healthy controls (HC). STEC-HUS cases were classified as "severe" or "non-severe".

Solutions to expand microbiome sciences in the Caribbean Region: an insider's perspective.

The Caribbean harbors diverse genetic resources, yet microbiome research in the region remains poorly characterized. Addressing infrastructure and training challenges through collaborations and capacity building is vital. This article reflects on the obstacles facing microbiome research in the region and proposes solutions to ensure equitable participation in the global microbial research ecosystem.

Targeted Enrichment Sequencing Utilizing a Respiratory Pathogen Panel for Genomic Wastewater-Based Viral Epidemiology in Uruguay.

Human respiratory and enteric viruses are responsible for substantial morbidity and mortality worldwide. Wastewater-based epidemiology utilizing next-generation sequencing serves as an effective tool for monitoring viral circulation dynamics at the community level. However, these complex environmental samples are often laden with other microorganisms and host genomic material, which can hinder the sensitivity of viral detection.

Host metabolism balances microbial regulation of bile acid signalling.

Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development, metabolism, immune responses and cognitive function. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues.

Optimizing power grids: A valley-filling heuristic for energy-efficient electric vehicle charging.

The expansion of electric vehicles (EVs) challenges electricity grids by increasing charging demand, thereby making Demand-Side Management (DSM) strategies essential to maintaining balance between supply and demand. Among these strategies, the Valley-Filling approach has emerged as a promising method to optimize renewable energy utilization and alleviate grid stress. This study introduces a novel heuristic, Load Conservation Valley-Filling (LCVF), which builds on the Classical and Optimistic Valley-Filling approaches by incorporating dynamic load conservation principles, enabling better alignment of EV charging with grid capacity.

Pharmacokinetics of Methadone in Adult Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

Background: Cardiopulmonary bypass (CPB) induces profound physiological changes that may alter the pharmacokinetics of methadone. We aimed to describe the pharmacokinetics of an intravenous bolus of methadone racemate in adult patients undergoing heart surgery with CPB.

Methods: We prospectively studied 29 patients aged 45 to 75 years scheduled for cardiac surgery with CPB who received methadone 0.