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Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Methods: Hence, this study aims to screen for natural products' structural analogs as new drug candidates against leishmaniasis. We applied Computer-aided drug design (CADD) approaches, such as virtual screening, molecular docking, molecular dynamics simulation, molecular mechanics–generalized Born surface area (MM–GBSA) binding free estimation, and free energy perturbation (FEP) aiming to select structural analogs from natural products that have shown anti-leishmanial and anti-arginase activities and that could bind selectively against the Leishmania arginase enzyme. Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, and malvidin showed good results against arginase targets from three parasite species and negative results for potential toxicities. The echioidinin and malvidin ligands generated interactions in the active center at pH 2.0 conditions and hydrogen bonds enhancing enzyme–ligand coupling. Conclusions: This work suggests the potential anti-leishmanial activity of the compounds and thus can be further in vitro and in vivo experimentally validated.

AbstractIn the mid-twentieth century (1948–57), North America experienced a severe drought forced by cold tropical Pacific sea surface temperatures (SSTs). If these SSTs recurred, it would likely cause another drought, but in a world substantially warmer than the one in which the original event took place. We use a 20-member ensemble of the GISS climate model to investigate the drought impacts of a repetition of the mid-twentieth-century SST anomalies in a significantly warmer world. Using observed SSTs and mid-twentieth-century forcings (Hist-DRGHT), the ensemble reproduces the observed precipitation deficits during the cold season (October–March) across the Southwest, southern plains, and Mexico and during the warm season (April–September) in the southern plains and the Southeast. Under analogous SST forcing and enhanced warming (Fut-DRGHT, ≈3 K above preindustrial), cold season precipitation deficits are ameliorated in the Southwest and southern plains and intensified in the Southeast, whereas during the warm season precipitation deficits are enhanced across North America. This occurs primarily from greenhouse gas–forced trends in mean precipitation, rather than changes in SST teleconnections. Cold season runoff deficits in Fut-DRGHT are significantly amplified over the Southeast, but otherwise similar to Hist-DRGHT over the Southwest and southern plains. In the warm season, however, runoff and soil moisture deficits during Fut-DRGHT are significantly amplified across the southern United States, a consequence of enhanced precipitation deficits and increased evaporative losses due to warming. Our study highlights how internal variability and greenhouse gas–forced trends in hydroclimate are likely to interact over North America, including how changes in both precipitation and evaporative demand will affect future drought.

Obesity and overweight in early childhood have detrimental impacts on children's health and development. Changing policy, system and environmental features focused on physical activity and healthy eating behaviors as part of health promotion interventions can play a key role in prevention strategies in early childhood education settings. These types of changes can have broad reach and are often sustained over time, which allows for impact on children who enter the early childhood education setting year after year. However, there is currently a gap between the generation of evidence for health promotion programs and their application into practice. This study used qualitative methods to evaluate intervention-, organizational- and individual-level factors within a dissemination and implementation framework that may be related to the implementation of a health-promoting intervention in early childhood education settings. Intervention-level factors, including feasibility and adaptability, organizational-level factors, including staff and leadership engagement, and individual-level factors, including attitudes, skills and knowledge, were identified as constructs that impacted the successful implementation of the intervention. These findings provide insight into core dissemination and implementation constructs that should be targeted by obesity prevention interventions in early childhood education settings to ensure maximum impact on sustainable behavior change.

Abstract Tuberculosis screening programs commonly target areas with high case notification rates. However, this may exacerbate disparities by excluding areas that already face barriers to accessing diagnostic services. We compared historic case notification rates, demographic, and socioeconomic indicators as predictors of neighborhood-level tuberculosis screening yield during a mobile screening program in 74 neighborhoods in Lima, Peru. We used logistic regression and Classification and Regression Tree (CART) analysis to identify predictors of screening yield. During February 7, 2019–February 6, 2020, the program screened 29,619 people and diagnosed 147 tuberculosis cases. Historic case notification rate was not associated with screening yield in any analysis. In regression analysis, screening yield decreased as the percent of vehicle ownership increased (odds ratio [OR]: 0.76 per 10% increase in vehicle ownership; 95% confidence interval [CI]: 0.58–0.99). CART analysis identified the percent of blender ownership (≤ 83.1% vs > 83.1%; OR: 1.7; 95% CI: 1.2–2.6) and the percent of TB patients with a prior tuberculosis episode (> 10.6% vs ≤ 10.6%; OR: 3.6; 95% CI: 1.0–12.7) as optimal predictors of screening yield. Overall, socioeconomic indicators were better predictors of tuberculosis screening yield than historic case notification rates. Considering community-level socioeconomic characteristics could help identify high-yield locations for screening interventions.

Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper introduces an innovative approach to address the distribution network reconfiguration (DNR) challenge, aiming to reduce power loss through an advanced hyperbolic tangent particle swarm optimization (HT-PSO) method. This approach is distinguished by the adoption of a novel hyperbolic tangent function, which effectively limits the rate of change values, offering a significant improvement over traditional sigmoid function-based methods. A key feature of this new approach is the integration of a tunable parameter, δ , into the HT-PSO, enhancing the curve's adaptability. The careful optimization of δ ensures superior control over the rate of change across the entire operational range. This enhanced control mechanism substantially improves the efficiency of the search and convergence processes in DNR. Comparative simulations conducted on 33- and 94-bus systems show an improvement in convergence, demonstrating a more exhaustive exploration of the search space than existing methods documented in the literature based on PSO and variations where functions are proposed for the rate of change of values. [ABSTRACT FROM AUTHOR]

This analysis compares the energy efficiency and operational costs of combustion vehicles (Hyundai Accent 1.6 L and Chevrolet Sail 1.5 L) with the Nissan Leaf, an electric vehicle, under current fuel and electricity pricing in Ecuador. Combustion vehicles, converting gasoline into mechanical energy, demonstrate substantial energy losses, leading to higher operational costs, especially with recent gasoline price hikes to USD 2.722 per gallon. In stark contrast, the Nissan Leaf exhibits significantly greater energy efficiency, consuming only 15–20 kWh per 100 km, which translates to lower running costs (USD 11.20 to fully charge a 40 kWh battery). Despite the clear economic and environmental benefits of electric vehicles, their adoption in Ecuador is hampered by geographical challenges such as diverse terrain that can affect vehicle range and battery longevity. Moreover, the limited and uneven distribution of EV charging stations, mostly concentrated in urban areas, poses significant barriers. For broader implementation, a strategic expansion of the EV infrastructure and careful consideration of the national energy grid's capacity to support increased electric vehicle uptake are essential. Addressing these challenges is crucial for realizing the full potential of electric vehicles in enhancing Ecuador's sustainability and energy independence. [ABSTRACT FROM AUTHOR]

Heritage bridges constitute an integral feature of the urban landscape in numerous cities. However, it is common for these structures to surpass their life cycle, rendering them ill-equipped to withstand the dynamic demands of users and extreme events, particularly hydrological occurrences. This research presents a methodology for the assessment of heritage riverine bridges, with a focus on the Grau Bridge in Peru as a case study. The investigation commences with an exhaustive literature review, complemented by a historical examination, followed by a preliminary diagnosis. Subsequently, hydrological and hydraulic studies are presented, encompassing drone surveys of the riverbed and the bridge, soil analyses, and the application of 1D and 2D models in HEC-RAS. The outcomes of this comprehensive analysis reveal the high vulnerability of the Grau Bridge. Finally, strategic interventions for its conservation are recommended. [ABSTRACT FROM AUTHOR]

This study investigates the impact of temperature variations on the torque capacity of shrink-fit junctions in water-jacketed permanent magnet synchronous motors. Focusing on both baseline and improved designs; torque capacities were evaluated across a temperature range from −40 °C to 120 °C under different material conditions: Least material condition, nominal, and maximum material condition. The baseline design exhibited torque capacities from 7648 Nm to 9032 Nm at −40 °C, decreasing significantly to 549 Nm to 1533 Nm at 120 °C. The improved design showed enhanced performance, with torque capacities ranging from 8055 Nm to 9247 Nm at −40 °C and from 842 Nm to 1618 Nm at 120 °C. The maximum improvement was observed at 120 °C for least material conditions, with a 55.4% increase, and the minimum improvement at −40 °C for maximum material conditions, with a 2.4% increase. Our findings demonstrate a significant increase in torque capacity by up to 20% under varied thermal conditions. These results underscore the effectiveness of design modifications in enhancing thermal stability and torque capacity, making the improved design a more reliable choice for high-performance applications subject to significant thermal fluctuations. This research highlights the critical role of material selection, thermal management, and precise design adjustments in optimizing the performance and reliability of permanent magnet synchronous motors. [ABSTRACT FROM AUTHOR]

Brain activity in response to food cues following Roux-En-Y Gastric Bypass (RYGB) in binge eating (BE) or non-binge eating (NB) individuals is understudied. Here, 15 RYGB (8 BE; 7 NB) and 13 no treatment (NT) (7 BE; 6 NB) women with obesity underwent fMRI imaging while viewing high and low energy density food (HEF and LEF, respectively) and non-food (NF) visual cues. A region of interest (ROI) analysis compared BE participants to NB participants in those undergoing RYGB surgery pre-surgery and 4 months post. Results were corrected for multiple comparisons using liberal (p < 0.006 uncorrected) and stringent (p < 0.05 FDR corrected) thresholds. Four months following RYGB (vs. no treatment (NT) control), both BE and NB participants showed greater reductions in blood oxygen level-dependent (BOLD) signals (a proxy of local brain activity) in the dorsomedial prefrontal cortex in response to HEF (vs. LEF) cues (p < 0.006). BE (vs. NB) participants showed greater increases in the precuneus (p < 0.006) and thalamic regions (p < 0.05 corrected) to food (vs. NF). For RYGB (vs. NT) participants, BE participants, but not NB participants, showed lower BOLD signal in the middle occipital gyrus (p < 0.006), whilst NB participants, but not BE participants, showed lower signal in inferior frontal gyrus (p < 0.006) in response to HEF (vs. LEF). Results suggest distinct neural mechanisms of RGYB in BE and may help lead to improved clinical treatments.

Background: Our aim was to report on the use of an innovative technique for airway management utilizing a small diameter, short-cuffed, long orotracheal tube for assisting operative rigid bronchoscopy in critical airway obstruction. Methods: We retrospectively reviewed the clinical data of 36 patients with life-threatening critical airway stenosis submitted for rigid bronchoscopy between January 2008 and July 2021. The supporting ventilatory tube, part of the Translaryngeal Tracheostomy KIT (Fantoni method), was utilized in tandem with the rigid bronchoscope during endoscopic airway reopening. Results: Indications for collateral intubation were either tumors of the trachea with near-total airway obstruction (13), or tumors of the main carina with total obstruction of one main bronchus and possible contralateral involvement (23). Preliminary dilation was necessary before tube placement in only 2/13 patients with tracheal-obstructing tumors (15.4%). No postoperative complications were reported. There was one case of an intraoperative cuff tear, with no further technical problems. Conclusions: In our experience, this innovative method proved to be safe, allowing for continuous airway control. It enabled anesthesia inhalation, use of neuromuscular blockage and reliable end-tidal CO2 monitoring, along with protection of the distal airway from blood flooding. The shorter time of the procedure was due to the lack of need for pauses to ventilate the patient.

Background: Changing "Policy, System, and Environmental" features focused on physical activity and healthy eating behaviors can play a key role in obesity prevention strategies in early childhood education settings because of their broad reach and because they can be sustained over time. The primary aims of this study were to examine the implementation and sustainability of health-promoting PSE changes after facilitation of an innovative strategic planning process in child care settings. Methods: The evidence-based policy, system, and environment change process is a strategic planning tool derived from intervention mapping that involves convening interdisciplinary wellness teams at child care settings to implement healthy eating and physical activity-related policy changes. The process was conducted with 43 wellness teams representing 68 child care centers. Results: The average number of health-promoting evidence-based changes implemented across all child care centers was 5.07; the most common type of changes were environment changes. Overall, 42% of changes were partially implemented and 47% of changes were fully implemented at 6 months. Head Start wellness teams implemented 1.52 fewer health-promoting changes compared to private fee-based wellness teams (p < 0.05). Conclusions: Identifying health-promoting policy, system and environment changes that are most readily implemented and sustained in child care centers can inform systems-level interventions and resource allocation related to early childhood obesity. This strategic planning process is a successful tool to translate sustainable changes related to healthy eating and physical activity, improve the quality rating of diverse child care centers, and promote healthy behaviors in early childhood.

Abstract Background Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lung, after 60 post-operative completely uneventful days, underwent genome-wide bulk RNA-Sequencing (RNA-Seq). Results Histological analysis showed dilation of air spaces and rupture of interalveolar septa. In addition, mild inflammation, no fibrosis, radial stretch of the bronchus, strong enlargement of airspaces and thinning of the blood supply were observed. Bioinformatic analyses of bulk RNA-Seq data identified 553 Differentially Expressed Genes (DEGs) at adjusted P-value below 0.001, between pre- and post-pneumonectomy. The top 10 up-regulated DEGs were Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated DEGs were Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Leveraging digital cytometry tools, no difference in cellular abundance was found between the two experimental groups, while the analysis of cell type-specific gene expression patterns highlighted a striking predominance of macrophage-specific genes among the DEGs. DAVID-based gene ontology analysis showed a significant enrichment of “Extrinsic apoptotic signaling pathway” (FDR q = 7.60 × 10− 3) and “Response to insulin” (FDR q = 7.60 × 10− 3) genes, along with an enrichment of genes involved as “Negative regulators of DDX58/IFIH1 signaling” (FDR q = 7.50 × 10− 4) found by querying the REACTOME pathway database. Gene network analyses indicated a general dysregulation of gene inter-connections. Conclusion This translational genomics study highlighted the existence both of individual genes, mostly dysregulated in certain cellular populations (e.g., macrophages), and gene-networks involved in pulmonary reaction after left pneumonectomy. Their involvement in lung homeostasis is largely supported by previous studies, carried out both in humans and in other animal models (under homeostatic or disease-related conditions), that adopted candidate-gene approaches. Overall, the present findings represent a preliminary assessment for future, more focused, studies on compensatory lung adaptation, pulmonary regeneration and functional reload.

Purpose: To determine outcomes after adjuvant pelvic local radiation therapy (RT) +/− concurrent chemotherapy for T1 and T2 rectal carcinomas treated with local excision or polypectomy. Methods: We retrospectively identified adult patients with histologically proven T1 and T2 rectal adenocarcinoma, diagnosed incidentally at time of local excision or polypectomy between 01 January 2007 and 31 December 2019, and appropriately staged to confirm N0 M0 status. Patients were excluded if they had recurrent cancer or had received total mesorectal excision (TME): anterior resection (AR) or abdominoperineal resection (APR). Patient, tumour and treatment factors, together with disease and toxicity outcomes were collected from institutional medical records, correspondence and investigation reports. Descriptive statistical analyses were employed. The primary endpoint was loco-regional control and secondary endpoints were treatment-related toxicity, disease free survival, overall survival and rate of surgical salvage for pelvic recurrence. Results: The median age of the 15 eligible patients was 73 (range 49–82 years). There were 9 men (60%) and 6 women (40%). The majority had T1 disease (80%) and most had received endomucosal resection (80%). All patients received 43-52Gy (EQD2) to the primary and 43-48Gy (EQD2) to the pelvis with 46.6% receiving concurrent chemotherapy (infusional 5-FU or oral capecitabine). At median follow up of 51 months, there were no local or regional recurrences. One patient experienced an isolated distant relapse at 48 months without any locoregional recurrence. Conclusion: Our findings demonstrate good locoregional disease control with the use of adjuvant pelvic RT for T1 and T2 rectal adenocarcinoma initially treated with polypectomy or local (non-oncological) excision. These findings indicate that adjuvant pelvic RT may provide an alternative to TME surgery in patients with incidentally detected early rectal cancers.

ABSTRACT Staphylococcus epidermidis is a ubiquitous human commensal skin bacterium that is also one of the most prevalent nosocomial pathogens. The genetic factors underlying this remarkable lifestyle plasticity are incompletely understood, mainly due to the difficulties of genetic manipulation, precluding high-throughput functional profiling of this species. To probe the versatility of S. epidermidis to survive across a diversity of environmental conditions, we developed a large-scale CRISPR interference (CRISPRi) screen complemented by transcriptional profiling (RNA sequencing) across 24 diverse conditions and piloted a droplet-based CRISPRi approach to enhance throughput and sensitivity. We identified putative essential genes, importantly revealing amino acid metabolism as crucial to survival across diverse environments, and demonstrated the importance of trace metal uptake for survival under multiple stress conditions. We identified pathways significantly enriched and repressed across our range of stress and nutrient-limited conditions, demonstrating the considerable plasticity of S. epidermidis in responding to environmental stressors. Additionally, we postulate a mechanism by which nitrogen metabolism is linked to lifestyle versatility in response to hyperosmotic challenges, such as those encountered on human skin. Finally, we examined the survival of S. epidermidis under acid stress and hypothesize a role for cell wall modification as a vital component of the survival response under acidic conditions. Taken together, this study integrates large-scale CRISPRi and transcriptomics data across multiple environments to provide insights into a keystone member of the human skin microbiome. Our results additionally provide a valuable benchmarking analysis for CRISPRi screens and are a rich resource for other staphylococcal researchers. IMPORTANCE Staphylococcus epidermidis is a bacteria that broadly inhabits healthy human skin, yet it is also a common cause of skin infections and bloodstream infections associated with implanted medical devices. Because human skin has many different types of S. epidermidis, each containing different genes, our goal is to determine how these different genes allow S. epidermidis to switch from healthy growth in the skin to being an infectious pathogen. Understanding this switch is critical to developing new strategies to prevent and treat S. epidermidis infections.

Aesthetic aspects of drinking water, such as Taste and Odor (T&O), have significant effects on consumer perceptions and acceptability. Solving unpleasant water T&O episodes in water supplies is challenging, since it requires expertise and know-how in diagnosis, evaluation of impacts and implementation of control measures. We present gaps, challenges and perspectives to advance water T&O science and technology, by identifying key areas in sensory and chemical analysis, risk assessment and water treatment, as articulated by WaterTOP (COST Action CA18225), an interdisciplinary European and international network of researchers, experts, and stakeholders.