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Abstract Background Pyridoxine-dependent epilepsy is primarily characterized by early-onset refractory seizures. This condition can be caused by alpha-aminoadipic semialdehyde dehydrogenase deficiency due to a mutation in the ALDH7A1 gene, leading to the accumulation of certain substances that impact the production of various brain neurotransmitters and enzymes. Case presentation Our report presents the first documented case of pyridoxine dependency in Syria. The female infant, born to consanguineous parents, exhibited seizures on the second day of life. Despite the administration of multiple antiepileptic medications, seizures persisted. A comprehensive assessment, including metabolic evaluation, electroencephalography, and phenotypic characteristics of seizures, prompted genetic testing for pyridoxine-dependent epilepsy, which identified a homozygous likely pathogenic variant in the ALDH7A1 gene, confirming the diagnosis of this condition. Subsequently, the baby was put on oral pyridoxine, resulting in complete cessation of seizures. Conclusions Due to its rarity, this condition was initially overlooked and led to an inappropriate therapeutic approach. Pyridoxine dependency should be considered after the manifestation of refractory seizures, as increased awareness can enable early diagnosis, appropriate treatment, and avoid unnecessary use of antiepileptic drugs. However, predicting the long-term outcome remains challenging.

Abstract This study investigates the impact of habitual late calorie intake on glucose metabolism in adults with overweight or obesity and diet or metformin-controlled prediabetes or type 2 diabetes independently of body weight, fat mass, energy intake or diet composition. Participants (n = 26) were classified as Later Eaters (LE) if ≥45% daily calories were consumed after 5 pm and Early Eaters (EE) if not, based on daily caloric intake assessed over 2-wk. EE and LE did not differ in anthropometrics or daily energy intake, but LE consumed more carbohydrates (p = 0.038) and fats (p = 0.039) after 5 pm. Fasting glucose, insulin, and C-peptide did not differ between groups but LE exhibited higher glucose concentrations after an oral glucose tolerance test (p = 0.001), even after adjusting for body weight, fat mass, energy intake and diet composition (p

El objetivo de este estudio fue analizar las barreras y facilitadores que los estudiantes con discapacidad manifiestan en Educación Física y en el deporte en Chile, Colombia, España y Perú. Se diseñó un estudio de tipo exploratorio, correlacional y de alcance transversal donde participaron 362 niñas, niños y adolescentes con discapacidad de Chile (41.1 %), Colombia (14.6 %), España (11.6 %) y Perú (32.5 %), a quienes se les aplicó el cuestionario “Barriers and facilitators of sports in children with physical disabilities” (BaFSCH) en su versión traducida al español. Respecto a los resultados, el 72.7 % practica actividad física en la escuela, con una mayor tendencia en Colombia (88.7 % χ² = 11.17, p = .02), donde el 72.0 % lo hace en clase de Educación Física mientras que el 38 %, en talleres de actividad física y deporte. Los principales facilitadores de inclusión son los padres y tutores, junto a sus amistades en el espacio escolar, y las barreras se asocian a algún accidente o caída, y/o su discapacidad y/o deficiencia. A su vez, el sexo biológico (OR = 1.893, IC = 1.19-3.00, p = .007) se asocia a un facilitador para la práctica de la actividad física, mientras que ser estudiante con discapacidad intelectual (OR = .437, IC = .20 – .94, p = .03) y discapacidad física (OR = .298, IC = .15-.58, p = .0002) se asocia a una barrera para la inclusión. Con esta investigación se reveló que la clase de Educación Física es fundamental en la práctica de la actividad física en el espacio educativo para niñas, niños y adolescentes con discapacidad, al igual que el entorno, que se transforma en factor protector a nivel ambiental.

Abstract Structural and functional changes of the brain are assumed to contribute to excessive cocaine intake, craving, and relapse in cocaine use disorder (CUD). Epigenetic and transcriptional changes were hypothesized as a molecular basis for CUD-associated brain alterations. Here we performed a multi-omics study of CUD by integrating epigenome-wide methylomic (N = 42) and transcriptomic (N = 25) data from the same individuals using postmortem brain tissue of Brodmann Area 9 (BA9). Of the N = 1 057 differentially expressed genes (p

This study examines the English to Indonesian translation of emotional expressions depicted in Daniel Keyes’s novel “The Minds of Billy Milligan” and its Indonesian translation “24 Wajah Billy.” The primary objectives are to describe the emotional expressions portrayed by the main character and to analyze the methods applied in translating these emotional expressions from English to Indonesian. Employing David Krech’s emotional classification theory and drawing on Vinay and Darbelnet’s translation methods, this qualitative descriptive research identifies 28 emotional classification data in the novel. Eight types of emotion classifications were identified, including 13 instances of fear, 6 instances of anger, 3 instances of hate, 2 instances of happiness, 1 instance of pain, 1 instance of guilt and regret, 1 instance of pride and shame, and 1 instance of love. The translation applies six translation methods used in 39 instances borrowing, literal, transposition, modulation, equivalent, and adaptation. Each emotion is translated using different translation methods. The application of these six methods is divided into three variants: single with 18 instances, couplet with 9 instances, and triplet with 1 instance. The literal method is the most frequently used in translating emotional expression. The translation method aims to preserve the essence of the narrative from the source language to the target language.

The optimal cellular reservoir for the conservation and propagation of endangered poultry is acknowledged to be primordial germ cells (PGCs). This study aimed to evaluate and compare the efficacy of cryopreserving PGCs derived from purified sources and blood samples. The experimental design encompassed two treatment groups, each iterated six replication. Blood samples that had been filled with 500 µL of phosphate-buffered saline without Ca2+ and Mg2+ (PBS) underwent centrifugation at 1200 rpm for six minutes. The supernatant was discarded and the pellet was mixed with 500 µL 10% FBS-PBS and was then subdivided for cryopreservation and PGCs purification. Cryopreservation included the controlled freezing of blood and purified PGCs samples in Nalgene cryogenic vials with the incorporation of banker cells. Following thawing, statistical analyses revealed no significant variance in the mean PGCs count between purified PGCs and blood samples (p > 0.05). The percentages of PGCs mortality and the recovery rate demonstrated statistical significance (p < 0.05). Further investigations indicated that cryopreserving blood samples significantly increased the recovery rate of PGCs while decreasing post-thaw mortality. Morphology of PGCs from blood cryopreservation showed similar morphology to PGCs in general. The potential application of cell-based cryo-banking will contribute to the preservation of poultry genetic diversity for sustainability and adaptation to future poultry demands.

Introduction: Regulatory T cells (Treg cells) in a tumor environment and the expression of forkhead box P3 (FOXP3) in tumor cells have been associated with a poor prognosis. There are few studies evaluating Treg cells and FOXP3 in B-cell acute lymphoblastic leukemia (B-cell ALL). This study aimed to evaluate the frequencies of Treg cells in bone marrow (BM) and peripheral blood (PB) of patients with B-cell ALL and to determine their associations with the circulating cytokine profile and the expression of CXCR1 (IL-8 receptor) in Treg cells, as well as to compare FOXP3 expression in blasts of patients with B-cell ALL and normal lymphoid precursors. Methods: Samples of BM and PB from patients with B-cell ALL and healthy controls were studied. Treg cells, cytokines, FOXP3 and CXCR1 were evaluated using flow cytometry and analyzed. Results: A total of 20 patients with B-cell ALL and 10 healthy controls were included. In B-cell ALL patients, Treg cell frequencies increased significantly, with higher percentages in the PB. Absolute Treg cell counts were associated with absolute blast counts in the BM and PB and with an IL-8 concentration. The IL-8 and IL-6 levels were associated with the CXCR1 expression in PB Treg cells. In addition, a greater expression of FOXP3 was observed in leukemic blasts than in normal lymphoid precursors. Conclusions: These results suggest that the presence of Treg cells and cytokines in the tumor environment may correspond to mechanisms to evade the immune response. For that reason, it would be important to monitor these parameters in B-cell ALL to establish their effect on the disease prognosis.

Aim. To evaluate the possibilities of post-processing of multidetector computed tomography (CT) results in the non-invasive diagnosis of pancreatic fibrosis (PF). Materials and methods. The study included 165 patients aged 57.91±13.5 years who underwent preoperative CT during surgical treatment for chronic pancreatitis and pancreatic cancer from April 2022 to February 2024. The normalized contrast ratios of pancreatic tissue in the pancreatic (NCPP) and venous (NCVP) phases, as well as the contrast ratio (CR) were measured. Pathomorphological assessment of PF performed in tissues outside neoplasm or desmoplastic reaction by the Kloppel and Maillet scale. Results. The values of post-processing CT results were compared in groups with different degrees of PF. Mean CR values were significantly higher (p=0.001) in patients with severe PF (CR 1.16±0.65 HU) than in patients with mild PF (CR 0.78±0.31 HU). CR value significant increase (p=0.03) was found in patients with signs of inflammatory changes in the pancreas tissue (CR 1.14±0.6 HU) than in those without them (CR 0.81±0.3 HU). There were no significant differences between the values of NCPP and NCVP, and the degree of PF. Conclusion. The CR value increased in patients with severe degree of PF. There was a relationship between CR value increase and the radiological density of pancreatic tissue in non-contrast phase and presence of early signs of pancreatic inflammatory changes. Thus, there was a relationship between CT postprocessing results and morphological signs of PF, which can be used for pancreatic fibrosis non-invasive diagnosis and identification of additional signs of early chronic pancreatitis.

Aim. To study the association of comorbidities and treatment outcomes in tuberculosis (TB) patients. Materials and methods. A retrospective study includes all TB patients aged 18 years and older registered for treatment in Moscow in period 2021 the end of the 3rd quarter of 2022 using data of regional epidemiological TB monitoring system, a total of 3039 patients. The frequency and spectrum of comorbidities, its impact on the risk of adverse treatment outcome (ATO) and mortality using univariate and regression analysis were assessed. Results. Comorbidities were identified in 1528 (50.3%) patients (95% confidence interval – CI 48.5–52.1); HIV infection (18.0%), chronic nonspecific lung disease (9.6%) and cardiovascular disease (8.2%) were predominant. The presence of comorbid pathology increased the odds of uneffective treatment (odds ratio – OR 2.56, 95% CI 2.22–3.03) and death (OR 2.45, 95% СI 1.67–3.59). Independent risk factors for ATO were HIV infection (OR 4.10, 95% CI 3.36–5.10), substance use (OR 2.57, 95% CI 1.70–3.66), chronic nonspecific lung disease (OR 1.39, 95% CI 1.04–1.88), diabetes mellitus (OR 1.69, 95% CI 1.15–2.48), liver pathology (OR 2.10, 95% CI 1.46–3.03), mental illness (OR 2.01, 95% CI 1.32–3.06). The death rate was 13.4%; the most significant predictors of mortality were HIV infection (OR 3.89, 95% CI 2.42–6.22) and liver disease (OR 1.90, 95% CI 1.27–2.82). A comorbidome model was constructed to assess the importance of different comorbidities for patient prognosis. Conclusion. The presence of comorbidity (predominantly HIV infection and liver disease) is a significant risk factor for ATO and mortality in TB patients, which should be taken into account when organizing and providing TB care to comorbid patients.

The main objective was to evaluate the use of common bean flour (CBF), corn flour, and semolina to obtain instant noodles by means of a hot dry and frying process. The hot drying process was conducted at 60 °C for 4 h, and frying was conducted at 140 °C and 160 °C for 1 and 3 min. Proximate analysis, total phenolic content (TPC), the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test, the oxygen radical absorbance capacity (ORAC) assay, phenolic acids and flavonoids profile by UPLC-ESI-MS/MS, the optimal cooking time (OCT), and color and texture analysis (TPA) were conducted. The general linear model and regression analysis were used. The incorporation of CBF resulted in an elevated protein content and TPC of the noodles. The noodles (hot dry) with CBF exhibited an enhanced antioxidant capacity. The adhesiveness has a direct correlation with the cinnamic, chlorogenic, and caffeic acid content (r2 = 0.95 or higher), as well as an inverse relationship with the vanillic, ferulic, and sinapic acids (r2 = −0.80 to −0.85). The dry hot noodles exhibited the lowest value of hardness (31.0 ± 1.5 N). The incorporation of common bean flour and corn flour enhances the nutritional profile of noodles. However, hot dry process affects their mechanical characteristics in comparison to the frying process.

Ischemic preconditioning (PC) induced by a sub-lethal cerebral insult triggers brain tolerance against a subsequent severe injury through diverse mechanisms, including the modulation of the immune system. Tumor necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), a hyaluronate (HA)-binding protein, has recently been involved in the regulation of the neuroimmune response following ischemic stroke. Thus, we aimed at assessing whether the neuroprotective effects of ischemic PC involve the modulation of TSG-6 in a murine model of transient middle cerebral artery occlusion (MCAo). The expression of TSG-6 was significantly elevated in the ischemic cortex of mice subjected to 1 h MCAo followed by 24 h reperfusion, while this effect was further potentiated (p < 0.05 vs. MCAo) by pre-exposure to ischemic PC (i.e., 15 min MCAo) 72 h before. By immunofluorescence analysis, we detected TSG-6 expression mainly in astrocytes and myeloid cells populating the lesioned cerebral cortex, with a more intense signal in tissue from mice pre-exposed to ischemic PC. By contrast, levels of TSG-6 were reduced after 24 h of reperfusion in plasma (p < 0.05 vs. SHAM), but were dramatically elevated when severe ischemia (1 h MCAo) was preceded by ischemic PC (p < 0.001 vs. MCAo) that also resulted in significant neuroprotection. In conclusion, our data demonstrate that neuroprotection exerted by ischemic PC is associated with the elevation of TSG-6 protein levels both in the brain and in plasma, further underscoring the beneficial effects of this endogenous modulator of the immune system.

Environmental DNA (eDNA) includes a set of rapidly emerging technologies that have the potential to support environmental monitoring and biodiversity conservation through novel, non-invasive, cost-effective and democratic methods and tools. Meanwhile, eDNA researchers are developing international standards for eDNA technologies, methods and data outputs. For eDNA technologies to be accessible, useful and appropriate, we must ensure that any standards developed include a broad conception of users from around the world, a diversity of ecological contexts and locations and, most importantly, a realistic outlook on research capacities and infrastructure. In this article, we assemble perspectives on international standardisation of eDNA from a diverse and global group of users and experts from Africa, South America and the Pacific Islands. The authors of this article collaborated by answering and discussing a set of open-ended questions aimed at eliciting hopes, concerns and experiences regarding eDNA standards. The result is a set of emergent themes and a generative consensus to highlight the need for the creation of adaptable standards, the development of regional capacity, increased sensitising to data sovereignty and the viewing of standardisation as a global capacity-building activity.

Background and Aim: Rice straw, a widely available agricultural byproduct globally, has significant potential as a basal diet for livestock. The major challenge lies in obtaining high-protein foliage that can be easily extracted using natural water rather than chemical solvents. This study aimed to assess the ability of distilled water to extract protein concentrate from Indigofera leaves (Indigofera zollingeriana Miq.) and to evaluate its effectiveness in enhancing rumen feed fermentation and digestibility in low-quality rice straw basal diets. Materials and Methods: The study was conducted in two experimental series. Experiment 1 was designed to explore the ability of distilled water to extract protein concentrate from fresh and dry Indigofera leaves by comparing it with the 0.1 N NaOH standard solvent. Experiment 2 focused on the in vitro digestibility of protein concentrates extracted from fresh Indigofera leaves based on optimal findings from experiment 1. Five treatments consisting of 0.5% and 1.0% protein concentrate and two extractants (distilled water and 0.1 N NaOH) were used to extract protein from Indigofera leaves. These extracts were then added to rice straw-based diets. Rice straw without supplements was used as a control. The treatments were arranged using a randomized complete design with five replicates. Results: The results of experiment 1 showed that distilled water was superior to 0.1 N NaOH for extracting protein concentrate from fresh Indigofera leaves, as revealed by higher dry matter, protein yield, total amino acids (AA), and total essential AA (EAA) production. For in vitro experiment 2, supplementation with distilled water-extracted protein concentrates successfully increased rumen fermentation and digestibility in rice straw basal diets, as indicated by higher gas production, total volatile fatty acid, and microbial protein levels compared with 0.1 N NaOH. Conclusion: Findings from this study confirm that Indigofera leaf protein concentrate offers a new alternative for enhancing rumen feed fermentation and the digestibility of low-quality rice straw diets. This study implies that it is an easy, cost-effective, and environmentally friendly approach, particularly beneficial for smallholders, to extract protein concentrate from fresh Indigofera leaves using distilled water and use it to enhance the quality of rice straw for ruminant feed. The limitation of this study is that the Indigofera supplement was established using in vitro digestibility under controlled laboratory conditions, which does not reflect real rumen conditions. Therefore, further studies using in vivo digestibility in ruminant animals are required to confirm the ability of the protein extracted from indigofera to enhance rumen feed fermentation in low-protein basal diets.

Abstract Background Initiatives aiming to assess the impact of rare diseases on population health might be hampered due to the complexity of disability-adjusted life years (DALYs) estimation. This study aimed to give insight into the epidemiological data sources and methodological approaches used in studies that estimated DALYs for chronic non-communicable rare diseases (CNCRD), and compare its results. Methods A literature strategy was developed for peer-review search in Embase and Medline, and also performed on grey literature databases and population health and/or rare disease-focused websites. We included studies that determined the burden of CNCRD listed on the Orphanet’s and/or the Genetic and Rare Diseases information center (GARD) websites. We excluded communicable and occupational diseases, rare cancers, and cost-effectiveness/benefit studies. Two researchers independently screened the identified records and extracted data from the final included studies. We used the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) statement to assess the quality of reporting of the included studies. The data synthesis depicted the studies’ characteristics, their distribution by geographic coverage and the group of disease(s) they focused on, the methods and data input sources used and estimated DALY per case. Results In total, 533 titles were screened, and 18 studies were included. These studies covered 19 different CNCRDs, of which most fell in the disease category “Diseases of the nervous system”. Diverse methodological approaches and data input sources were observed among burden of CNCRD studies. A wide range of DALY per case was observed across the different studies and diseases included. Conclusions A low number of burden of CNCRD studies was observed and most estimates resulted from multi-country studies, underlining the importance of international cooperation to further CNCRD research. This study revealed a lack of epidemiological data and harmonization of methods which hampers comparisons across burden of CNCRD studies.

Abstract Background Acute myeloid leukemia (AML) is characterized by the abnormal proliferation of myeloid precursor cells and presents significant challenges in treatment due to its heterogeneity. Recently, the NLRP3 inflammasome has emerged as a potential contributor to AML pathogenesis, although its precise mechanisms remain poorly understood. Methods Public genome datasets were utilized to evaluate the expression of NLRP3 inflammasome-related genes (IL-1β, IL-18, ASC, and NLRP3) in AML patients compared to healthy individuals. CRISPR/Cas9 technology was employed to generate NLRP3-deficient MOLM-13 AML cells, followed by comprehensive characterization using real-time PCR, western blotting, FACS analysis, and transmission electron and immunofluorescence microscopy. Proteomic analyses were conducted to identify NLRP3-dependent alterations in protein levels, with a focus on the eIF2 kinase PERK-mediated signaling pathways. Additionally, in vivo studies were performed using a leukemic mouse model to elucidate the pathogenic role of NLRP3 in AML. Results Elevated expression of NLRP3 was significantly associated with diminished overall survival in AML patients. Genetic deletion, pharmacological inhibition and silencing by RNA interference of NLRP3 led to decreased AML cell survival through the induction of apoptosis. Proteomic analyses uncovered NLRP3-dependent alterations in protein translation, characterized by enhanced eIF2α phosphorylation in NLRP3-deficient AML cells. Moreover, inhibition of PERK-mediated eIF2α phosphorylation reduced apoptosis by downregulating pro-apoptotic Bcl-2 family members. In vivo studies demonstrated reduced leukemic burden in mice engrafted with NLRP3 knockout AML cells, as evidenced by alleviated leukemic symptoms. Conclusion Our findings elucidate the involvement of the NLRP3/PERK/eIF2 axis as a novel driver of AML cell survival. Targeting NLRP3-induced signaling pathways, particularly through the PERK/eIF2 axis, presents a promising therapeutic strategy for AML intervention. These insights into the role of the NLRP3 inflammasome offer potential avenues for improving the prognosis and treatment outcomes of AML patients.

Abstract Cell-free DNA (cfDNA) has emerged as a pivotal player in precision medicine, revolutionizing the diagnostic and therapeutic landscape. While its clinical applications have significantly increased in recent years, current cfDNA assays have limited ability to identify the active transcriptional programs that govern complex disease phenotypes and capture the heterogeneity of the disease. To address these limitations, we have developed a non-invasive platform to enrich and examine the active chromatin fragments (cfDNAac) in peripheral blood. The deconvolution of the cfDNAac signal from traditional nucleosomal chromatin fragments (cfDNAnuc) yields a catalog of features linking these circulating chromatin signals in blood to specific regulatory elements across the genome, including enhancers, promoters, and highly transcribed genes, mirroring the epigenetic data from the ENCODE project. Notably, these cfDNAac counts correlate strongly with RNA polymerase II activity and exhibit distinct expression patterns for known circadian genes. Additionally, cfDNAac signals across gene bodies and promoters show strong correlations with whole blood gene expression levels defined by GTEx. This study illustrates the utility of cfDNAac analysis for investigating epigenomics and gene expression, underscoring its potential for a wide range of clinical applications in precision medicine.

Societal Impact Statement Maize is one of the most consumed grains worldwide. Its production and international trade are expected to continue increasing because of its use as animal fodder and direct human food. Although maize's history spans millennia, in the last century it underwent significant changes due to genetic engineering, particularly during the Green Revolution. Due to maize's importance for current food security and energy production, it is fundamental to understand this engineering process to assess the implications of current styles of maize production for local and global landscapes, scientific institutions, and transnational networks of agricultural science. Summary This article aims to explain how Mexican agricultural expertise contributed to the development of cytogenetics as a specialized field in the study of the diversity of maize within the framework of the Green Revolution. To this end, the article follows the work of Mexican agronomist Takeo Ángel Kato Yamakake within the activities of the Inter‐American Maize Improvement Program (IMIP), formally established in 1960. By reconstructing the debate on the genetic implications of chromosomal structure and function, this study contributes to the historiography devoted to the role played by local experts in the classification, experimentation, and conservation of maize. The article is based on sources from Mexico and the United States, an interview with Kato, and the consultation of the database “Rockefeller Fellows. Individual Mobility Awards at Rockefeller‐endowed Organizations, 1914‐1970.” Kato's trajectory provides an overview of agronomy in Mexico and shows the relevance of transnational exchange in the establishment of plant cytogenetics. Kato's academic activity features collaborations with key figures such as Edwin Wellhausen, Albert Longley, Barbara McClintock, W. Gallinat, Czeslawa Prywer, and Almiro Blumenschein. A Green Revolution era quest to unravel the origin of maize as a way of perfecting its genetic manipulation fueled the interest in establishing cytogenetics in Mexico. However, the irruption of the molecular approach made the study of the position of chromosomal knobs less of a priority. Despite this, classical cytogenetics, under Kato's leadership, remains a field that contributed to the knowledge of the vegetal genome, even when the IMIP disappeared and the logic of the Green Revolution lost its centrality.

This study employs a cost-efficient method to create a pliable BC/rGO-NiCo-LDH electrode film on a bacterial cellulose base. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX) analyses verified the incorporation of reduced graphene oxide (rGO) and nickel–cobalt layered double hydroxide (NiCo-LDH) into the bacterial cellulose structure. The BC/rGO-NiCo-LDH composite material exhibited high-temperature stability and achieved a specific capacitance of 311 F g−1 at a scan rate of 0.1 mV/s, surpassing that of earlier cellulose electrodes. The electrode film showed exceptional mechanical capabilities, displaying flexibility and load resistance without any structural damage. The film’s flexibility and lightweight properties were improved due to the low density of 0.656 g cm−3, which is a result of the nanoporous structure and intrinsic low density of rGO and cellulose. A retention ratio of 0.40 for storage modulus at a glass transition temperature of around 90°C demonstrated positive mechanical performance. This cost-effective and uncomplicated synthesis approach produced a BC/rGO-NiCo-LDH electrode with potential. The material possessed favourable mechanical and electrochemical characteristics, making it suitable for wearable electronics.

In current toxicological research, 2D cell cultures and animal models are well- accepted and commonly employed methods. However, these approaches have many drawbacks and are distant from the actual environment in human. To embrace this, great efforts have been made to provide alternative methods for non-animal skin models in toxicology studies with the need for more mechanistically informative methods. This review focuses on the current state of knowledge regarding the in vitro 3D skin model methods, with different functional states that correspond to the sustainability in the field of toxicology testing. We discuss existing toxicology testing methods using in vitro 3D skin models which provide a better understanding of the testing requirements that are needed. The challenges and future landscape in using the in vitro 3D skin models in toxicology testing are also discussed. We are confident that the in vitro 3D skin models application may become an important tool in toxicology in the context of risk assessment.

Summary: Background: Surgical care holds significant importance in healthcare, especially in low and middle-income countries, as at least 50% of the 4.2 million deaths within the initial 30 days following surgery take place in these countries. The Lancet Commission on Global Surgery proposed six indicators to enhance surgical care. In Colombia, studies have been made using secondary data. However, strategies to reduce perioperative mortality have not been implemented. This study aims to describe the fourth indicator, perioperative mortality rate (POMR), with primary data in Colombia. Methods: A multicentre prospective cohort study was conducted across 54 centres (hospitals) in Colombia. Each centre selected a 7-day recruitment period between 05/2022 and 01/2023. Inclusion criteria involved patients over 18 years of age undergoing surgical procedures in operating rooms. Data quality was ensured through a verification guideline and statistical analysis using mixed-effects multilevel modelling with a case mix analysis of mortality by procedure-related, patient-related, and hospital-related conditions. Findings: 3807 patients were included with a median age of 48 (IQR 32–64), 80.3% were classified as ASA I or II, and 27% of the procedures had a low-surgical complexity. Leading procedures were Orthopedics (19.2%) and Gynaecology/Obstetrics (17.7%). According to the Clavien–Dindo scale, postoperative complications were distributed in major complications (11.7%, 10.68–12.76) and any complication (31.6%, 30.09–33.07). POMR stood at 1.9% (1.48–2.37), with elective and emergency surgery mortalities at 0.7% (0.40–1.23) and 3% (2.3–3.89) respectively. Interpretation: The POMR was higher than the ratio reported in previous national studies, even when patients had a low–risk profile and low-complexity procedures. The present research represents significant public health progress with valuable insights for national decision-makers to improve the quality of surgical care. Funding: This work was supported by Universidad del Rosario and Fundación Cardioinfantil-Instituto de Cardiología grant number CTO-057-2021, project-ID IV-FGV017.

Atrial cardiomyopathy and remodeling play pivotal roles in the development of atrial fibrillation (AF) and heart failure (HF), involving complex changes in atrial structure and function. These changes facilitate the progression of AF and HF by creating a dynamic interplay between mechanical stress and electrical disturbances in the heart. Sodium–glucose cotransporter 2 inhibitors (SGLT2is), initially developed for the management of type 2 diabetes, have demonstrated promising cardiovascular benefits, being currently one of the cornerstone treatments in HF management. Despite recent data from randomized clinical trials indicating that SGLT2is may significantly influence atrial remodeling, their overall effectiveness in this context is still under debate. Given the emerging evidence, this review examines the molecular mechanisms through which SGLT2is exert their effects on atrial remodeling, aiming to clarify their potential benefits and limitations. By exploring these mechanisms, this review aims to provide insights into how SGLT2is can be integrated into strategies for preventing the progression of atrial remodeling and HF, as well as the development of AF.

Zoo conditions are unique for reindeer, since domestic reindeer are not kept in captive facilities like cattle. In the zoo, reindeer are usually surrounded by many different animals that they would never encounter naturally. Thus, they might be infected with new helminths. Numerous petting zoos raise concerns about the safety of tactile interactions for human visitors. Our study is the first large-scale one. Qualitative and quantitative fecal analyses were carried out for 233 reindeer distributed over 50 Russian zoos according to the National Standard of the Russian Federation (GOST R 54627-2011) Ruminant animals—Methods of Laboratory Helminthological Diagnostics. Where possible, DNA analyses of helminths were performed targeting internal transcribed spacer region. As a result, F. hepatica, Paramphistomum sp., Moniezia sp. (including M. expansa), gastrointestinal strongylids (including Nematodirus spp.), Dictyocaulus sp., E. rangiferi, Trichuris sp., and Capillaria sp. were found in 106 (45%) zoo reindeer. All these helminths were previously reported in reindeer and pose no direct danger for humans. The intensity of invasions was mostly low. Fecal examination might be considered as an indirect method for mange diagnostics, as Chorioptes and Demodex mites were found in reindeer fecal samples. The latter may represent a novel species of mite specific for reindeer.

Abstract The demersal fish orange roughy (Hoplostethus atlanticus) can live for up to 250 years, twenty times more than its congener silver roughy (Hoplostethus mediterraneus). Studies of Hoplostethus have focused mainly on its ecology and conservation due to its vulnerability to commercial fishing. In this work, we present the de novo genomes of orange and silver roughies and explore the genomic mechanisms that could contribute to such differential longevities. Using comparative genomics on a list of more than 400 genes, we identified gene candidates with differential residue changes in Hoplostethus that are related to genomic instability, disabled macroautophagy and intercellular communication. We hypothesized that these mechanisms could have been selected as adaptations to the deep environment and, as an epiphenomenon of these mechanisms, may have contributed to an extension of the lifespan of H. atlanticus.

Abstract Introduction People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years. Methods We conducted a qualitative study from February 2022 to March 2023, at three paediatric and adolescent HIV treatment centers in Uganda. In-depth interviews were conducted at TPT initiation and after completion for purposively selected health workers, adolescents aged 10–19 years living with HIV, and caretakers of children aged below 18years. Results The desire to avoid TB disease, previous TB treatment, encouragement from family members, and ministry of health policies emerged as key facilitators for the children and adolescents to initiate TPT. Barriers to TPT initiation included; TB and HIV-related stigma, busy carer and adolescent work schedules, reduced social support from parents and family, history of drug side effects, high pill burden and fatigue, and perception of not being ill. TPT completion was enabled by combined TPT and ART refill visits, delivery of ART and TPT within the community, and continuous education and counseling from health workers. Reported barriers to TPT completion included TB and HIV-related stigma, long waiting time. Non-disclosure of HIV status by caretakers to CALHIV and fear of side effects was cited by health workers as a barrier to starting TPT. Facilitators of TPT initiation and completion reported by healthcare workers included patient and caretaker health education, counselling about benefits of TPT and risk of TB disease, having same appointment for TPT and ART refill to reduce patient waiting time, adolescent-friendly services, and appointment reminder phone calls. Conclusion The facilitators and barriers of TPT initiation and completion among CALHIV span from individual, to health system and structural factors. Health education about benefits of TPT and risk of TB, social support, adolescent-friendly services, and joint appointments for TPT and ART refill are major facilitators of TPT initiation and completion among CALHIV in Uganda.

Background: Partial adrenalectomy (PA) is increasingly used to treat benign tumors to lower the probability of adrenal insufficiency and reduce need for lifetime hormone replacement therapy. Currently, two major concerns are increased bleeding and non-functioning adrenal remnants. This paper examines these concerns and compares surgical approaches with novel findings. Methods: Between 1993 and 2023, 72 patients underwent PA for primary adrenal disorders. Demographic, clinicopathologic and outcome data were analyzed for summary statistics, confidence intervals, and heteroscedastic t-test statistics. Results: The patients were 17–76 years-old and were 59.7 % female. The PA was on the left 54.2 % and bilaterally 4.2 %. The indications were adrenal adenoma, pheochromocytoma, cyst, hyperplasia, and other. The mean tumor diameter was 2.7 cm (range 0.7-10 cm). 23 were performed open, 43 laparoscopically, and 6 with an intended robotic approach. Median follow-up was 9.3 years.Robotic had the shortest length of stay (LOS) (p-value 0.01), then laparoscopic (p-value 0.00004), then open. The estimated blood loss (EBL) ranged from 5 to 500 mL (median 50 mL). The median LOS was two days.Intra-operative complication rate was 1.4 % and readmission within 30 days occurred in 2.8 %. Out of 72 patients, 6.8 % needed hormone replacement; of the 14 patients with contralateral adrenalectomy, 28.6 % needed replacement. Conclusion: PA appears to be safe with both laparoscopic and robotic-assisted techniques with superior perioperative outcomes. The functional results of PA prevent most patients from requiring ongoing steroid replacement treatment and recurrence rates were low. PA should be advised for more frequent use as the preferred treatment method of choice. Key message: Partial adrenalectomies' perioperative and long-term outcomes over a median 9.3 year follow-up emphasized its safety and efficacy with 95 % CI of (2.7 cm, 3.6 cm) for masses with adrenal sufficiency post-resection. Additionally, as healthcare institutions decide whether to invest in surgical robots, robotic approach's outperformance of laparoscopic and open on LOS may be counterbalanced by laparoscopic's strong performance in low EBL.

Abstract Background Tuberculosis (TB) infectiousness decreases significantly with only a few days of treatment, but delayed diagnosis often leads to late treatment initiation. We conducted a sequential explanatory mixed methods study to understand the barriers and facilitators to prompt diagnosis among people with TB. Methods We enrolled 100 adults who started TB treatment in the Carabayllo district of Lima, Peru, between November 2020 and February 2022 and administered a survey about their symptoms and healthcare encounters. We calculated total diagnostic delay as time from symptom onset to diagnosis. We conducted semi-structured interviews of 26 participants who had a range of delays investigating their experience navigating the health system. Interview transcripts were inductively coded for concepts related to diagnostic barriers and facilitators. Results Overall, 38% of participants sought care first from public facilities and 42% from the private sector. Only 14% reported being diagnosed with TB on their first visit, and participants visited a median of 3 (interquartile range [IQR] health facilities before diagnosis. The median total diagnostic delay was 9 weeks (interquartile range [IQR] 4–22), with a median of 4 weeks (IQR 0–9) before contact with the health system and of 3 weeks (IQR 0–9) after. Barriers to prompt diagnosis included participants attributing their symptoms to an alternative cause or having misconceptions about TB, and leading them to postpone seeking care. Once connected to care, variations in clinical management, health facility resource limitations, and lack of formal referral processes contributed to the need for multiple healthcare visits before obtaining a diagnosis. Facilitators to prompt diagnosis included knowing someone with TB, supportive friends and family, referral documents, and seeing a pulmonologist. Conclusions Misinformation about TB among people with TB and providers, poor accessibility of health services, and the need for multiple encounters to obtain diagnostic tests were major factors leading to delays. Extending the hours of operation of public health facilities, improving community awareness and provider training, and creating a formal referral process between the public and private sectors should be priorities in the efforts to combat TB.

Abstract Background Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D. Methods Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers. Results In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25–75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356–568), 11.8% (10.1–13.4) and 0.50 µg/L (0.30–0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period. Conclusion The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change.

Abstract Transcription-blocking DNA lesions are specifically targeted by transcription-coupled nucleotide excision repair (TC-NER), which removes a broad spectrum of DNA lesions to preserve transcriptional output and thereby cellular homeostasis to counteract aging. TC-NER is initiated by the stalling of RNA polymerase II at DNA lesions, which triggers the assembly of the TC-NER-specific proteins CSA, CSB and UVSSA. CSA, a WD40-repeat containing protein, is the substrate receptor subunit of a cullin-RING ubiquitin ligase complex composed of DDB1, CUL4A/B and RBX1 (CRL4CSA). Although ubiquitination of several TC-NER proteins by CRL4CSA has been reported, it is still unknown how this complex is regulated. To unravel the dynamic molecular interactions and the regulation of this complex, we apply a single-step protein-complex isolation coupled to mass spectrometry analysis and identified DDA1 as a CSA interacting protein. Cryo-EM analysis shows that DDA1 is an integral component of the CRL4CSA complex. Functional analysis reveals that DDA1 coordinates ubiquitination dynamics during TC-NER and is required for efficient turnover and progression of this process.

Abstract Background With the introduction of transcatheter aortic valve implantation, the role of surgical aortic valve replacement (SAVR) in elderly patients has been called into question. We investigated the short-term outcomes of SAVR in the elderly population. Methods All patients aged ≥ 70 years who underwent isolated SAVR in our centre between 2008 and 2017 were included in the study. Survival at 30 days and 1 year were compared for patients aged 70–79 years (n = 809) versus patients aged ≥ 80 years (n = 322). Factors associated with poorer survival outcomes were identified using multivariable Cox regression analysis. Results Patients aged 70–79 years and patients aged ≥ 80 years had similar survival rates at 30 days (98.1% vs. 98.4%, p = 0.732) and 1 year (96.0% vs. 94.1%, p = 0.162) post-SAVR. This remained true after multivariable adjustment. Risk factors for 30 day all-cause mortality included insulin dependent diabetes (HR 6.17, 95% CI 1.32–28.92, p = 0.021) and increasing cardiopulmonary bypass time (HR 2.72, 95% CI 1.89–3.91, p

Abstract Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we have developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are highest in liver tissue, which is also a hub for lipid production. While the loss of GSH does not cause liver failure, it decreases lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we find that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver’s balance of redox buffering and triglyceride production.

Abstract In many parts of the world, domestic and wild animal populations interact at the interface between natural and agricultural ecosystems. Introduced with the first inhabitants arriving from eastern Africa, the bushpig (Potamochoerus larvatus) is the largest living terrestrial mammal in Madagascar. Bushpigs are regularly reported close to human settlements where they damage crops and gardens. As domestic pigs are often raised in free-ranging conditions around the villages, bushpigs and domestic pigs can interact leading to the transmission and circulation of shared swine pathogens that impact both animal and human health. In this study, we characterized the socio-ecological context of bushpig–domestic pig interactions in two different regions of western Madagascar. We conducted participatory mapping sessions and focus group interviews with 65 hunters, 80 pig farmers and 96 crop farmers in 20 fokontany, the smallest administrative unit in Madagascar. After discussing with participants, we gathered information about the spatialization of interactions and their potential geographical drivers. We explored data by performing multiple correspondence analysis and hierarchical clustering on principal components. Based on the reported occurrence or absence of bushpig-domestic pig interactions we were able to classify areas with high or intermediate levels of interactions or no interactions at all. Interactions between the two pig species were reported in only 25% of the fokontany assessed. Even though both suid species were attracted to fruit trees, crops, and water sources, only indirect interactions in those spots were reported. Direct interactions were reported in 10% of cases and referred to interspecific sexual and/or agonistic behavior. The participatory methods used to acquire local knowledge about natural events were confirmed as valuable, low-cost exploratory methods to characterize areas with wild-domestic animal interactions. The results of this study will help plan future studies to characterize the interface between the two species from an ecological or epidemiological perspective using more sensitive and sophisticated ecological approaches.

INTRODUCTION: Diabetes and hyperglycemia are major risk factors that can increase infarction volume and contribute to poor functional status. Our study aim was to investigate the effect of stress hyperglycemia on various safety and efficacy outcomes in patients with large vessel occlusions (LVOs) undergoing mechanical thrombectomy (MT) with or without diabetes. METHODS: A retrospective analysis of consecutive LVO patient data treated with MT at a Comprehensive Stroke Center in the Mid-South was conducted. Adult patients with LVO on computed tomography angiography (CTA) and treated with MT within 24 h of symptom onset were included. The primary outcome was to determine if there was an association in collateral flow or infarct size in the setting of hyperglycemia. Secondary outcomes included National Institute of Health Sciences Score (NIHSS) and Modified Rankin Score (mRS). RESULTS: A total of 450 patients underwent MT, out of which 433 had baseline hemoglobin A1c recorded: mean age: 64 ± 15 years, 47% women, pretreatment NIHSS median 15 points (interquartile range 10–19), 323 (75%) with good collaterals grades >2 on multiphasic CTA, 326 (75%) were non-diabetic, and 107 (25%) were diabetic. Nondiabetics with stress hyperglycemia had a tendency toward higher pre-treatment NIHSS scores (mean 17.5 ± 7.6, P = 0.02) and at 24-h (12.9 ± 9.0, P = 0.02), poor collaterals (multiphasic CTA score ≥2; 21.4% vs. 34.5%, P = 0.02), larger infarct volumes (50.7 ± 63.6 vs. 24.4 ± 33.8 cc, P < 0.0001), and had poorer functional outcomes (good mRS 0–2 47.7% vs. good mRS 0–2 36.8%) when compared to nondiabetics without stress hyperglycemia. For every 1 mg/dL increase in admission blood glucose, there was a 0.3 cc increase in infarct volume (95% confidence intervals for β =0.2–0.4; P < 0.0001) after adjusting for the final thrombolysis in cerebral infarction score. CONCLUSIONS: LVO patients with stress hyperglycemia without previously diagnosed diabetes had more severe strokes, developed larger infarct volumes, poorer collaterals, and had worse functional outcomes at 90 days post-MT. In addition, LVO patients with diabetes and stress hyperglycemia exhibited more passes during MT and worse functional outcomes.

Plectranthus scutellaroides is a plant with attractive colored leaves. It contains secondary metabolite compounds such as flavonoids and phenolics, which provide skin protection against ultraviolet rays from the sun. The research aims to investigate the activity of P. scutellarioides leaf extract from various variants and different solvents on sunscreen, skin lightening, and anti aging activities. The best extract is formulated in gel dosage form. Each P. scutellaroides leaf was extracted using ethanol, ethyl acetate, and hexane as solvents. The obtained extract was assessed for Sun Protecting Factor (SPF), UVA Protection grade (PA), antioxidant activity, and inhibition of tyrosinase, collagenase, elastase, and hyaluronidase. Determination was conducted in vitro using spectrophotometric methods. The highest sunscreen activity was observed in the ethanol extract Va (Va-ET), which exhibited SPF and PA values of 25.618±0.265, and 0.681±0.007 (star 3), respectively at a concentration of 100 ug/mL. The most significant skin-lightening activity was observed in the ethanol extract Vc (Vc-ET), with an IC50 value inhibiting tyrosinase of 39.059 ug/mL. Regarding the anti-aging activity of the extracts, as determined by their antioxidant activity and inhibition of collagenase, elastase, and hyaluronidase, the most promising extracts were obtained from ethanol extract Va (Va-ET) and ethyl acetate extract Va (Va-EA), with IC50 values of 79.734, 76.838, 143.384, and 122.467 ug/ mL, respectively. The Va-ET was formulated into a gel dosage form, and there was a significant effect of the gelling agent on the SPF value of the extract after formulation (p < 0.05). All extracts exhibit activity as sunscreen, skin lightening, and anti-aging, with the Va-ET showing the highest efficacy. Gelling agents significantly influence the SPF value of extracts after formulation into the gel dosage form. Among them, F3, formulated from the Va-ET of P. scutellaroides using Carbopol-940 as a gelling agent, exhibits the highest efficacy.

Background and Aim: With the emergence of severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), antiviral drug development has gained increased significance due to the high incidence and potentially severe complications of the resulting coronavirus infection. Heterocycle compounds, acting as antimetabolites of DNA and RNA monomers, rank among the most effective antiviral drugs. These compounds’ antiviral effects on various SARS-CoV-2 isolates, as found in existing data collections, form the basis for further research. The aim of this study was to examine the possible antiviral effect of some originally synthesized heterocyclic compounds. Materials and Methods: The main methods were cell culturing, cytotoxicity assay, qRT-PCR assay, tissue and blood cells analysis, and micro-computed tomography (micro-CT) imaging. Results: In both in vitro and in vivo conditions, the elimination of SARS-Cov-2 occurred significantly earlier after administration of the compounds compared to the control group. In hamsters, the primary symptoms of coronavirus disease disappeared following administration of heterocycle compounds. Conclusion: Using delta and omicron strains of the SARS-CoV-2 virus, newly created heterocycle compound analogs dramatically reduced SARS-CoV-2 multiplication, resulting in a drop in viral RNA load in the supernatant under in vitro conditions. Improvements in pathological manifestations in the blood, bone marrow, and internal organs of hamsters demonstrated that heterocycle compounds inhibited SARS-CoV-2 replication both in vitro and in vivo.

Abstract Alzheimer’s Disease (AD) pathology has been increasingly explored through single-cell and single-nucleus RNA-sequencing (scRNA-seq & snRNA-seq) and spatial transcriptomics (ST). However, the surge in data demands a comprehensive, user-friendly repository. Addressing this, we introduce a single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD). It offers a broader spectrum of AD-related datasets, an optimized analytical pipeline, and improved usability. The database encompasses 1,053 samples (277 integrated datasets) from 67 AD-related scRNA-seq & snRNA-seq studies, totaling 7,332,202 cells. Additionally, it archives 381 ST datasets from 18 human and mouse brain studies. Each dataset is annotated with details such as species, gender, brain region, disease/control status, age, and AD Braak stages. ssREAD also provides an analysis suite for cell clustering, identification of differentially expressed and spatially variable genes, cell-type-specific marker genes and regulons, and spot deconvolution for integrative analysis. ssREAD is freely available at https://bmblx.bmi.osumc.edu/ssread/ .

Background: Spontaneous intestinal perforation is the second most common cause of neonatal bowel perforation. The major dilemma for neonatologists and pediatric surgeons may be caused by NEC and severe SIP may have comparable physical examination findings, as well as radiological examinations showing pneumoperitoneum. Case: This case report describes a five-day-old boy brought by his parents to the ED because of abdominal distension that had occurred for the past two days. Physical examination showed a moderate general condition, CRT

ObjectivesThe present study aimed to determine oral health (OH) related knowledge, attitudes, and practices among Public Health (PH) and Nutrition (NU) students at Qatar University.MethodA cross-sectional study was conducted using a pre-validated questionnaire comprising 36 items covering demographics, knowledge, attitudes and perception of oral health practices. Data were analyzed descriptively (means, standard deviations, proportions) and inferentially using statistical tests including t-tests for comparing means, and chi-square tests for examining associations between categorical variables.ResultsA total of 112 female undergraduate students participated, including 41 from PH and 71 from NU programs (response rate for both courses = 59.5%). The mean age was 21.8, while 23% were Qataris and 77% non-Qataris. Overall, students demonstrated good knowledge of OH (67.65%), with the PH group scoring higher (70.7%) than NU (65.35%). Knowledge regarding dental plaque was low for both groups (31.0%). Attitudes toward OH varied among participants. Most students reported practicing brushing with fluoridated toothpaste and demonstrated high knowledge regarding the association between poor OH and general health (95%).ConclusionOverall, PH and NU undergraduate students exhibited relatively good knowledge of OH, however, demonstrated a range of attitudes and practices, including suboptimal ones. Integration of OH education into the PH and NU curriculum is warranted, along with enhanced interprofessional education to promote self-awareness and improve patient oral health outcomes.

Este artículo de investigación indaga por indicadores que permitan identificar formas de regular el aprendizaje en el aula, y examina la relación entre estas formas y la disposición del estudiante frente a la heterorregulación ejercida por el profesor. Participaron en el estudio 189 estudiantes universitarios colombianos, quienes respondieron un cuestionario compuesto por cuatro escalas: autorregulación, arregulación, desregulación y disposición a la heterorregulación. El análisis muestra un patrón de correlaciones en donde, en una dirección, se encuentra la escala de autorregulación, y en otra, las escalas de arregulación y desregulación. Un resultado muy sugerente es la ausencia de relación entre la autorregulación y la disposición a la heterorregulación.

The use of back-to-back built-up channel beams in cold-formed steel (CFS) structures is steadily rising. The growing demand for CFS sections as a cost-effective design solution has driven the development of these CFS built-up sections. Despite this, there has been limited research on the performance of mild steel (MS) based CFS at high temperatures, particularly regarding its flexural behavior. This study thoroughly explores the behavior of MS-based CFS beams with different spans under high temperatures, followed by cooling with air or water. It assesses the impact of thermal loading and evaluates the effectiveness of these cooling methods. Experimental findings are validated and analyzed in conjunction with Finite Element Modeling (FEM) using ABAQUS and the Direct Strength Method (DSM). The study also conducts a parametric analysis to determine how the varying span that affects flexural capacity of beam. Among beams heated to the same temperature, those cooled with water exhibit slightly lower load capacities than those cooled with air. The maximum load observed is 91.21 kN for the reference specimen, while the minimum load is 39.82 kN for the specimen heated for 90 min and cooled with water, resulting in a 78.45% difference between these values. Additionally, as heating duration increases, ductility of beam also increases. Various failure modes are observed based on different heating and cooling conditions across different beam spans. This study offers valuable insights into the performance of MS-based CFS beams under thermal stress and different cooling conditions, providing important data for structural design and safety in construction.

ABSTRACT Due to recent improvements, Nanopore sequencing has become a promising method for experiments relying on amplicon sequencing. We describe a flexible workflow to generate and annotate high-quality, full-length 16S rDNA amplicons. We evaluated it for two applications, namely, (i) identification of bacterial isolates and (ii) species-level profiling of microbial communities. We assessed the identification of single bacterial isolates by sequencing, using a set of barcoded full-length 16S rRNA gene primer pairs (pair A), on 47 isolates encompassing multiple genera and compared those results with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based identification. Species-level community profiling was tested with two sets of barcoded full-length 16S primer pairs (A and B) and compared to the results obtained with shotgun Illumina sequencing using 27 stool samples. We developed a Nextflow pipeline to retain high-quality reads and taxonomically annotate them. We found high agreement between our workflow and MALDI-TOF data for isolate identification (positive predictive value = 0.90, Cramér’s V = 0.857, and Theil’s U = 0.316). For species-level community profiling, we found strong correlations (rs > 0.6) of alpha diversity indices between the two primer sets and Illumina sequencing. At the community level, we found significant but small differences when comparing sequencing techniques. Finally, we found a moderate to strong correlation when comparing the relative abundances of individual species (average rs = 0.6 and 0.533 for primers A and B). Despite identified shortcomings, the proposed workflow enabled accurate identification of single bacterial isolates and prominent features in microbial communities, making it a worthwhile alternative to MALDI-TOF MS and Illumina sequencing.IMPORTANCEA quick, robust, simple, and cost-effective method to identify bacterial isolates and communities in each sample is indispensable in the fields of microbiology and infection biology. Recent technological advances in Oxford Nanopore Technologies sequencing make this technique an attractive option considering the adaptability, portability, and cost-effectiveness of the platform, even with small sequencing batches. Here, we validated a flexible workflow to identify bacterial isolates and characterize bacterial communities using the Oxford Nanopore Technologies sequencing platform combined with the most recent v14 chemistry kits. For bacterial isolates, we compared our nanopore-based approach to matrix-assisted laser desorption ionization-time of flight mass spectrometry-based identification. For species-level profiling of complex bacterial communities, we compared our nanopore-based approach to Illumina shotgun sequencing. For reproducibility purposes, we wrapped the code used to process the sequencing data into a ready-to-use and self-contained Nextflow pipeline.

Decolonization initiatives in design have sparked growing interest among academics worldwide. While these initiatives foster collaborative design with diverse communities in Latin America, their theories and practices often diverge significantly. How to critically integrate these decolonial models into learning processes and knowledge creation with other communities within the university? To address these questions, we undertake a reflexive critical literature review from an artisanal perspective, moving away from objective systems and standardized measurements of knowledge, integrating our experiences, and highlighting our concerns as educators and students from the Global South. This review highlights two key themes in decolonial studies literature: understanding power relations and the roles in knowledge production, and identifying prevailing ideas and practices in knowledge creation with other entities. Using this information, we establish a three-way conversation to examine the limits of neoliberal modern-colonial education within reflexive critical practice, drawing on our own experiences and positionalities.

IntroductionOur study set out to identify the benefits for veterinary workers of structured daily well-being practices on compassion satisfaction, burnout, and secondary traumatic stress. Suggested origins of high rates of psychological stress and burnout are significant occupational concerns for veterinary workers. Many professional helpers experience an extreme state of tension and preoccupation from exposure to the suffering of those being helped. Veterinary workers are further impacted by negative associations and moral distress experienced due to limitations in the provision of quality medical care for veterinary patients. These negative experiences exist despite veterinary professionals’ work being worthwhile and highly valued.MethodsA randomized controlled study was performed over 6 months. Volunteer participants were members of a team of veterinary workers at a 24-h emergency and specialty hospital. Study participants were asked to incorporate daily well-being practice(s) into existing routines whereas control participants were not. Measures of well-being and the negative impacts of serving as veterinary helpers were assessed by having participants complete the Professional Quality of Life (ProQOL) self-assessment at baseline and at 1, 3 and 6 months. Composite scores for compassion satisfaction, burnout and secondary traumatic stress were calculated.ResultsBaseline ProQOL scores were similar between study participants and controls. Baseline compassion satisfaction (CS), burnout scores (BS), and secondary traumatic stress (STS) scores for those instituting well-being practices were 37.6 (+/− 3.6), 26 (+/− 5.3), and 26.6 (+/− 5.2). Study participants had higher compassion satisfaction scores at 6 months with mean CS scores (n = 15) of 40.1 (+/− 6.8) and adjusted scores that were on average 3.0 (95% CI 0–6.1) higher than the control group (p = 0.048). Significant differences in BS or STS scores were not seen.DiscussionImprovements were seen in CS but not BO/STS for those caregivers who implemented well-being practices into their daily routines. Factors that likely contributed to successful implementation of well-being practices include educational resources, supportive leadership, accessibility, and consistent acknowledgement and positive rewards. Proposed supportive elements and resources for maintenance of well-being practices within a team of veterinary workers include provision of a psychologically safe community and team support (including formal or informal “buddy systems”).

BackgroundDigital technologies have penetrated most workplaces. However, it is unclear how such digital technologies affect the physical health of older workers. ObjectiveThis scoping review aims to examine and summarize the evidence from scientific literature concerning the impact of digital technology on the physical health of older workers. MethodsThis scoping review will be conducted following recommendations outlined by Levac et al and will adhere to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews) guidelines for reporting. Peer-reviewed papers written in English will be searched in the following databases: MEDLINE, Cochrane, ProQuest, Web of Science, Scopus, APA PsycInfo, and ERIH PLUS. The web-based systematic review platform Covidence will be used to create a data extraction template. It will cover the following items: study and participant characteristics, health measures, digital tool characteristics and usage, and research findings. Following the Population, Concept, and Context (PCC) framework, our review will focus on studies involving older workers aged 50 years or older, any form of digital technology (including teleworking and the use of digital tools at work), and how digital technologies affect physical health (such as vision loss, musculoskeletal disorders, and migraines). Studies that focus only on mental health will be excluded. Study selection based on title and abstract screening (first stage), full-text review (second stage), and data extraction (third stage) will be performed by a group of researchers, whereby each paper will be reviewed by at least 2 people. Any conflict regarding the inclusion or exclusion of a study and the data extraction will be resolved by discussion between the researchers who evaluated the papers; a third researcher will be involved if consensus is not reached. ResultsA preliminary search of MEDLINE, Epistemonikos, Cochrane, PROSPERO, and JBI Evidence Synthesis was conducted, and no current or ongoing systematic reviews or scoping reviews on the topic were identified. The results of the study are expected in April 2025. ConclusionsOur scoping review will seek to provide an overview of the available evidence and identify research gaps regarding the effect of digital technology and the use of digital tools in the work environment on the physical health of older workers. International Registered Report Identifier (IRRID)PRR1-10.2196/59900

Objective To provide an update on the key characteristics, refinements to project flow, and future opportunities for a program providing customized research evidence to health system policymakers and providers. Approach With a goal to inform health system decision making, the program answers research questions posed by health system requestors that can be answered with linked, population-based administrative data. Now in its 10th year of operation, the program has been refined over time to improve efficiency, usefulness of research products, and requestor satisfaction. Satisfaction surveys and individual-level engagements with requestors are used to collect feedback on the needs of an increasingly diverse group of requests. Results With 508 requests, 82 Data Sharing Agreements, and 257 unique requestors since its inception, the program informs governmental decision making, evaluates intervention effectiveness, and aids grassroots organizations’ planning for services. Notable updates to the program include, inserting multiple opportunities for connection between the program and requestors through the project life cycle to understand goals and needs; assigning staff scientists to shepherd projects and promote efficiency; training coordinators to review privacy impact assessments; and (soon) accepting a broader range of projects to include data beyond the health sector e.g. education. Conclusion This program continues to improve and is an exemplar of sustainable approaches to supporting health system requestors with evidence from administrative data in program evaluation, planning and policy change. Implications Being responsive to requestor needs has allowed the program to attract an increasingly diverse range of requesters who can obtain impactful and timely research evidence.

Objectives To understand changes in prescription patterns over time, and support dental and oral health program planning, Toronto Public Health issued an AHRQ request to collect information on physician-prescribed medications following an oral health-related incident. Approach An algorithm was created to identify oral health-related incidents among children and youth aged up to 17 years old in Ontario and Toronto during fiscal years 2013 to 2022. The algorithm used provincial data on physician visits, emergency department visits, inpatient hospitalizations, or day surgeries to define ‘dental-related incidents’. Physician-prescribed medications (e.g., chlorhexidine, opioids, benzodiazepines, antibiotics, NSAIDs and others) within seven days of a dental-related incident were recorded using Ontario Drug Benefit Claims and the Narcotics Monitoring System. Results Of 522,674 dental-related incidents in Ontario between 1 April 2013 and 31 March 2023, 9.2% had physician-prescribed medications (versus 8.6% of 90,810 dental-related incidents in Toronto). The proportion of incidents with prescriptions increased from 6.4% in 2013 to 10.7% in 2022 in Ontario, and from 5.9% to 10.3% in Toronto. The most prescribed medication was antibiotics, followed by immediate-release combination medications and non-long-acting medications. Conclusions/Implications Over the 10-year period examined, an increasing proportion of dental-related incidents had physician-prescribed medications, which may be attributed to the implementation of Ontario’s pharmacare program (OHIP+) in 2018. Early access to routine and preventative dental care could become more accessible as part of Canada’s new federal dental program. Results from this AHRQ will inform better resource allocation in dental and oral health program planning, potentially reducing avoidable healthcare costs.

Objectives An Applied Health Research Question request from Peel Public Health was investigated, to provide a comprehensive overview of injury patterns and healthcare utilization, among cyclists and pedestrians in the Peel Region of Ontario. Approach Emergency department visits and hospitalizations across the Peel region were analyzed from 2018 to 2022, and categorized by collision type (pedestrian, cyclist motor vehicle collision (MVC), and cyclist non-MVC). Data was segmented quarterly and annually, and further stratified by residence status, sex, and age, by linking individuals to other administrative health databases. Additionally, 30-day mortality outcomes were evaluated. To contextualize incidence rates with population demographics, Public Health Data Zone and Census Subdivision data were also utilized. Results For ambulatory visits, a substantial majority of Peel residents received treatment within the region, evidenced by 4,483 cyclist visits (55%) and 1,338 pedestrian visits (50%). However, a noteworthy portion of Peel residents — 188 cyclists (45%) and 182 pedestrians (46%) — received treatment outside the region. Hospitalization patterns echoed these visits. Overall, non-MVCs accounted for a large proportion of cycling incidents, particularly among females, stressing the need for targeted safety measures. Still, survival rates post-incident were notable, with a 100% survival rate for cyclists after ambulatory visits. Pedestrian survival rates were similarly high. Conclusion This study provided valuable insights into patterns of pedestrian and cyclist injuries among Peel residents, revealing considerable cross-regional healthcare utilization. Implications Findings will be utilized by the Region of Peel and partner organizations, to enhance local road safety initiatives and service delivery for vulnerable road users.

In the Romanian legal system, usucaption is an original way of acquiring property rights. In court actions for the establishment of the existence of the right of ownership by virtue of usucaption, the question of the passive procedural quality has frequently been raised. The general rule is that the defendant is represented by the titleholder of the property to be usucaptioned. However, in practice there are different situations which need to be adapted to each individual situation. This paper aims to present the most common situations regarding the passive legal standing in actions for the establishment of ownership by virtue of usucaption.

This research is included in qualitative descriptive method research which aims to describe personalized learning by elementary school teachers by applying the book Simple Media in Learning. The steps that will be taken in this research are conducting a background analysis of the research carried out by analyzing elementary school teachers, about personalization of learning, and about Simple Media Books in Learning. The second step is to formulate the problems that occur in the field. The third step, determine the research objectives. The fourth step, collect data in the field. Fifth, process the data that has been collected in the previous stage. And the last thing is to draw conclusions about how to personalize elementary school teachers learning through Simple Media Books in Learning. The results obtained on the personalization learning focus component and the need for personalization learning in the Simple Media in Learning book are very good, this can be seen from the data which shows that all sub-components have ratings of three and four, namely good and very good. As for the characteristics component of personalized learning, several inputs were obtained which can be used as material for improving the book. Abstrak Penelitian ini termasuk dalam penelitian metode deskriptif kualitatif yang bertujuan untuk mendeskripsikan pembelajaran personalisasi oleh guru Sekolah Dasar dengan menerapkan buku Media Sederhana dalam Pembelajaran. Langkah-langkah yang akan dilakukan dalam penelitian ini yaitu melakukan analisis latar belakang penelitian yang dilakukan dengan menganalisis guru sekolah dasar, tentang personalisasi belajar, dan tentang Buku Media Sederhana dalam Pembelajaran. Langkah kedua adalah merumuskan permasalahan yang terjadi di lapangan. Langkah ketiga, menentukan tujuan penelitian. Langkah keempat, mengumpulkan data di lapangan. Kelima, mengolah data yang telah dikumpulkan pada tahap sebelumnya. Dan yang terakhir adalah membuat kesimpulan tentang bagaimana personalisasi belajar guru SD melalui Buku Media Sederhana dalam Pembelajaran tersebut. Hasil yang diperoleh pada komponen fokus personalization learning dan kebutuhan personalization learning pada buku Media Sederhana dalam Pembelajaran sudah sangat baik, hal ini terlihat dari data yang menunjukan seluruh sub komponen memiliki penilaian tiga dan empat, yaitu baik dan baik sekali. Adapun pada komponen karakteristik personalization learning diperoleh beberapa masukan yang dapat dijadikan sebagai bahan perbaikan buku.

Abstract Background The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010. Methods We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE). Results In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for “HIV/AIDS and sexually transmitted diseases” and “transport injuries” (each -19%). “Diabetes and kidney diseases” showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, “mental disorders” showed an increasing age-standardised YLL rate (14.5%). Conclusions There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease.