SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dis-autonomy tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2-vaccination of healthy controls (N = 89, 71 females, mean/ median age 39/ 49 years) were compared with corresponding values of PACVS-affected persons (N= 191, 159 females, mean/median age: 40/39 years) exhibiting chronic fatigue/dis-autonomy (≥ three symptoms for ≥ five months after last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases of 11 receptor-antibodies (by 25 - 50 %, p < 0.0001), increases in two receptor-antibodies (by 15 - 25 %, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p &lt; 0.0001) by increased angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/ml, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/ml, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/ml, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers

Conventional models do not fully explain composition of the solar system – for example, the presence of p-nuclei and post-post-Fe-nuclei remains not yet understood (and is one of the great unresolved puzzles of nuclear astrophysics in general); other puzzles exist. We offer a hypothesis which can explain the appearance of non-native elements in the solar system, and a feasible scenario for its implementation. The hypothesis suggests that a nuclear-fission "event" occurred in the inner part of the solar system at the time currently defined as the birth of the system. Conventional models have never considered fission as a contributing nuclei-production mechanism. Upon examination of the existing models and factual data (presented in volumes of publications but never combined into an aggregate), we identified one plausible scenario by which a fission event (not demolishing the entire solar system) could occur: an encounter with a compact super-dense stellar "fragment" (with specific properties) and its "explosion" in fission-cascades. Such scenario also helps resolve other long-standing puzzles of the solar system. For example, it provides that the fission-produced nuclei subsequently transformed into the material that (eventually) accreted into the "rocky" objects in the system (terrestrial planets, asteroids, etc.) and enriched the pre-existed hydrogen-helium objects (the Sun and the gaseous giants) – this offers an explanation for the planets’ inner position and compositional differences within the predominantly hydrogen-helium rest of the solar system. Other implications also follow.

Purpose: Post-pandemic management of COVID-19 infections and any emergent outbreaks is as an endemic disease remains a public health concern. Vaccine hesitancy may continue to hamper efforts to respond any new disease outbreaks and future epidemics. This qualitative study aimed to explore factors influencing covid-19 vaccine acceptance and hesitancy in Kenya too gain deeper insights on this issue. Methods: The study was implemented in Western Kenya using key informant interviews. Fourteen (14) key informants were purposively selected for the study. All interviews were transcribed and analyzed using thematic analysis. Interpretation of findings was done within the framework of the Health Belief Model. Key findings: Knowledge was a critical factor in combatting misinformation and fostering vaccine acceptance among participants in this study. Misinformation included rumors that the vaccine lowers immunity and was intended for population control. Cues to action included influence from political and opinion leaders and observing the loss of life among unvaccinated individuals. Perceived barriers to vaccine uptake included fear of vaccine safety, side effects, long waiting times at that time of our study, fear of contracting the COVID-19 at vaccination sites, family/spousal influence on vaccine uptake and fear of the unknown with the vaccine. Conclusion: Findings from this study provides insight into areas for targeted strategies for managing Covid-19 vaccinations and future pandemics. Within the framework of the Health Belief Model, this study identified salient barriers and facilitators of COVID-19 vaccine hesitancy that may be helpful to inform future pandemic response.

In the era of the post-quantum Internet of Things (IoT), the implementation of anti-quantum cryptographic algorithms in numerous terminals can successfully defend against prospective quantum computing assaults. Lattice-based cryptography can withstand quantum computing attacks, making it a viable substitute for the currently prevalent classical public-key cryptographic technique. Nevertheless, the algorithm’s significant time complexity will result in a substantial computational burden on the edge computing chip in the IoT terminal. The computation of polynomial multiplication is the most demanding task in lattice-based cryptographic algorithms. Therefore, the investigation into efficient methods for calculating polynomial multiplication is highly important. Quick number theory transformations (NTT) are a widely employed technique to accelerate polynomial multiplication. This study presents a hardware implementation of an efficient number theory transformation. We utilize a multi-level pipeline architecture in the design to accomplish parallel calculations and execute it on a low-profile Artix7-XC7A100T FPGA device. The performance evaluation results demonstrate that our implementation significantly enhances performance and reduces resource usage compared to other existing proposals on the same platform. We suggested NTT core can be implemented in edge computing chips to enhance computational speed due to its small and low-latency design. The experimental results show that the proposed design, which supports both NTT and inverse NTT, achieves 417-Megahertz and consumes only 541-LUTs on Artix-7 XC7A100T.

Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one third of adults with AML. AML NPM1mut is recognized as a separate entity in the World Health Organization (WHO) classification of AML. Clinical and survival data suggest that patients with this form of AML often have a more favorable prognosis, which may be due to the immunogenicity created by the mutations in the NPM1 protein. Consequently, AML with NPM1mut can be considered an immunogenic subtype of AML. However, the underlying mechanisms of this immunogenicity and associated favorable survival outcomes need to be further investigated. Immune checkpoint molecules, such as the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, play important roles in leukemogenesis through their maintenance of an immunosuppressive tumor microenvironment. Preclinical trials have shown that the use of PD-1/PD-L1 (PDx) checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with NPM1mut AML may be better suited to immunogenic strategies that are based on the inhibition of the immune checkpoint pathway of PDx than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PDx inhibitors.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

Open pit mining is a common activity in the Yucatan peninsula for the extraction of limestone. This mining is known under the generic name of quarries, and regionally as sascaberas (sascab=white soil in Mayan language). These areas are characterized by the total removal of the natural vegetation cover and soil in order to have access to the calcareous material. The present study shows the composition and structure of the vegetation in five quarries after approximately ten years of abandonment, and the conserved vegetation near to each one of the quarries in southeastern Quintana Roo. Using a canonical correspondence analysis (CCA), the distribution of the species was determined in relation to the edaphic variables: soil depth, percentage of organic matter (OM), cationic exchange capacity (CEC), pH and texture. 26 families, 46 genera and 50 species were recorded in the quarries and 25 families, 45 genera and 47 species were recorded in the conserved areas. The dominant species in the quarries belong to the families Poaceae, Fabaceae, Rubiaceae and Anacardiaceae. The quarries with higher values of OM (1.63%), CEC (24.05 Cmol/kg), depth (11 cm) and sand percentage (31.33%) include the following species like Lysiloma latisiliquum, Metopium brownei and Bursera simaruba which are commonly found in secondary forests. On the other hand, quarries with lower values of OM (0.39%), CEC (16.58 Cmol/kg) and depth (5.02), and higher percentage of silt (42.44%) were dominated by herbaceous species belonging to the Poaceae family and by Borreria verticillata, which are typical in disturbed areas of southeastern Mexico. In all cases, the pH was slightly alkaline due to the content of calcium carbonate (CaCO3), characteristic of the soils of the region. The edaphic variables are significantly correlated with the development and distribution of vegetation, and with the structure of the communities.

Volunteering has many social, emotional and health benefits and could be an option for people with younger/early onset dementia to engage in stage/age-appropriate, personally meaningful activity within their local community. Audio data of people with young onset dementia discussing their volunteering experiences were taken from the Dementia Diaries and co-analysed. This study explored how people with dementia volunteer in the UK, the benefits and barriers, and how we can improve access to volunteering opportunities. The findings suggest that stigma is the overarching concept (or net) which influences people’s experiences of volunteering with dementia. Within the stigma net, three themes were developed that employed a lifespan approach to challenging said stigma: 1) Valuing the past, 2) Valuing the present and 3) Valuing the future, each with additional subthemes. This research contributes to the limited pool of literature that highlights the clear benefits of volunteering for people with young onset dementia, while also considering how dementia stigma can create practical and institutional barriers to accessing volunteering. Guidance is provided for how to deliver meaningful and accessible volunteering opportunities.

Background: Patients with burn scars often suffer from a ‘vicious cycle’ in which their skin becomes dry and pruritus. This greatly reduces patients' quality of life, but there is no well-known mechanism yet, and the development of drugs for effective treatment is necessary. Objective: This study evaluated the efficacy and safety of cosmetic formulation containing arginine glutamate ion pair (named as RE:pair) on epidermal barrier function and reducing pruritus. Materials and Methods: A total of 20 patients [15 male and 5 female; average age 48.35 ± 13.13 years] participated in evaluating the effectiveness of using the RE:pair formula topically twice daily for up to 4 weeks after burn pruritus. Treatment efficacy was evaluated by Numerical Rating Scale (NRS) for itching and pain, transepidermal water loss (TEWL), skin hydration, Vancouver Scar Scale (VSS) evaluation, and the patient’s overall satisfaction. Results: This formula was well-tolerated, with significant relief of NRS for itching and pain score after 2nd weeks and 4th weeks of application (p &lt; 0.05). The itching score was high in some patients, and overall, it decreased significantly after 4 weeks compared to before application. Also, the personal pain score decreased after 4th weeks. Overall TEWL showed 35 % improvement after 4th week, and 52 % improvement was confirmed in arms and 19 % in legs. The overall improvement effect of skin hydration was also 45 % (p = 0.0012), and the improvement effect was 40 % (p = 0.0371) in areas including arms and 54 % (p = 0.0313) in areas including legs. All patient satisfactory evaluations were "excellent". Conclusions: RE:pair formula was safe and effective in improving skin barrier and itch relief, and if further studies are conducted, it can be used as an excellent topical treatment for post-burn scar that strengthens the skin barrier.

The role of inflammation in the pathophysiology of acute myocardial infarction (AMI) is well established. Recognizing inflammation's pivotal role in AMI, this manuscript systematically traces historical studies, spanning from early attempts to the present landscape. Several anti-inflammatory trials targeting inflammation in post-AMI have been performed. The review includes key trials, examining their designs, patient demographics, and primary outcomes. Efficacy and challenges are analyzed, shedding light on the translational implications of trial outcomes. The article also discusses emerging trends, ongoing research, and potential future directions in the field. Practical applications and implications for clinical practice are considered, providing a holistic view of the evolving landscape of anti-inflammatory interventions in the context of AMI.

After the end of colonial rule in 1997, the Hong Kong education system has been experiencing a policy reform on Senior Secondary Education (NSS) Curriculum commenced in September 2009 aiming to educate students as globalized Hong Kong citizens for the Western. Although previous scholars argued that it is hard to differentiate between domestic values and the Western values in account of curriculum development (Sewpaul, 2007), this study demonstrates an analysis using the dichotomy to investigate how local curriculum, especially in the post-colonial areas, embrace both the Western values and domestic values. Using content analysis on the NSS curriculum guides, this article evaluates the influence of the Western values and Chinese values in the NSS curriculum through investigating: (1) how the Western values and Chinese values was incorporated into the curriculum throughout its development (2) why some values are more significantly highlighted in the curriculum guide. Findings include that more Chinese values are involved in the curriculum documents. This may be because of the upholding of domestic values as a post-colonial city. The Western values which are academically related are greatly incorporated into the local curriculum.

In this study, the team employed full-scale crash tests to investigate the impact of post-densification technology on the safety performance of separated central median W-beam barriers under low compaction conditions. By precisely simulating the design and construction environment of the central median, the study comprehensively evaluated the barrier's containment, redirection, buffering, and anti-intrusion performances, as well as the deformation of both the barrier and vehicles under various collision scenarios. The results indicate that under low compaction soil conditions, the A-level separated central median barriers reinforced with post-densification technology effectively meet the specified protection requirements. By comparing the influence of soil strength variations on barrier performance under simulated rainfall conditions, it was confirmed that enhancing soil compaction significantly improves soil stability, effectively increases the overall strength and stability of the barriers, reduces deformation, and significantly enhances safety performance. This study not only validates the effectiveness of the reinforcement scheme but also provides new perspectives for the scientific research of safety barriers and offers crucial technical support for the optimal design of road safety protection facilities.

Sustainable manufacturing practices are becoming increasingly necessary due to the growing concerns regarding climate change and resource scarcity. Consequently, material recycling technologies have gradually become preferred over conventional processes. This study aimed to recycle waste polylactic acid (PLA) from household-disposed cups and lids to create 3D-printed parts and promote sustainable manufacturing practices. To achieve this, the current study utilised virgin and post-consumer PLA (sourced from household waste) blends. The PC-PLA wastes were shredded and sorted by size with the aid of a washing step, resulting in a filament with a 1.70 ± 0.5 mm diameter without fragmentation or dissolution. A 50:50 wt.% blend of virgin PLA (vPLA) and PC-PLA was selected as the standard recycling percentage based on previous research and resource conservation goals. The study investigated the impact of three 3D printing parameters (layer height (LH), infill density (I), and nozzle temperature (NT))on the quality of 3D-printed parts using a three-level L9 Taguchi orthogonal array. The findings revealed that blending PC-PLA with vPLA led to significant improvements in the tensile, flexural, and impact strengths by 18.40%, 8%, and 9.15%, respectively, compared to those of recycled PLA. This conclusion was supported by the investigation of the fracture surface area, which revealed fractographic features associated with printing parameters, such as plastic deformation and interfilament debonding. An ANOVA analysis revealed a positive influence of larger layer height and high nozzle temperature on the mechanical properties. Subsequently, the optimal printing parameters (LH: 0.3 mm, I: 100%, and NT: 215 °C) were determined using the S/N ratio, and a confirmation test using the optimum printing parameters exhibited a strong correlation with statistically predicted outcomes. Finally, the study used optimum printing parameters to fabricate 100% post-consumer recycled PLA 3D printed parts, demonstrating their potential for low-strength applications. Based on these findings, it can be concluded that virgin and post-consumer recycled PLA blended filament for fabricating 3D printed components is an effective way to support plastic recycling in the context of a circular economy.

The seismic events of 2015 in Nepal exposed the challenges associated with constructing earthquake-resistant 2-story self-built stone masonry structures in high-elevation rural regions, especially post-disaster. The Department of Urban Development and Building Construction (DUDBC) provided designs that failed to preserve the local architectural landscape and craftsmanship while adding unfamiliar knowledge and technology. To address the challenges related to architecture, structure, and socio-economic concerns in designing and implementing post-earthquake houses, a need-based building development framework is required for standardized practice. This study presents a novel framework to assess, design, and implement a self-built house after a disaster, consisting of five stages: 1) post-disaster problem assessment, 2) need identification, 3) material selection, 4) design development, and 5) validation and implementation. Based on this framework, we proposed a novel gabions building construction technology for two-story stone masonry structures that effectively mitigate post-disaster challenges such as logistic, resilience, and socioeconomic aspects while improving disaster resiliency specifically in the high-elevation rural areas of Nepal. The proposed two-story gabion building preserves architectural values, enhances structural integrity, and provides cost-effectiveness when compared with its DUDBC peer models while providing much-needed relief to the vulnerable community. The proposed resilient house, G- 2.1, utilizes locally sourced materials and craftsmanship, and innovative gabion technology that ensures affordability and facilitates knowledge transfer. The contribution of this study includes a development framework and a two-story gabions house that is most suitable for self-built post-disaster reconstruction and resilient to local architecture and socio-economic conditions while providing structural integrity and safety.

This article provides a thorough overview of biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI), acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical application. The pathophysiological mechanisms underlying AKI, AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses, with the impact on renal injury. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and cellular senescence of renal cell. Key signaling pathways, such as Wnt/β-Catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The Renin-Angiotensin-Aldosterone System (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating oxidative stress and cellular changes that promote fibrosis. Clinical evidence suggests RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.

Background: The Risk of Paradoxical Embolism (RoPE) score was developed to identify stroke-related patent foramen ovale (PFO) in patients with cryptogenic stroke. Methods: We conducted a retrospective analysis of the 2016 to 2020 National Inpatient Sample to determine the performance of modified RoPE score for PFO presence in patients with acute ischemic stroke (AIS). Results: A total of 3,338,805 hospital admissions for AIS were analysed and 3.0% had PFO. Patients with PFO were younger compared to those without PFO (median 63 years vs. 71 years, p&lt;0.001) and fewer were female (46.1% vs. 49.7%, p&lt;0.001). The patients with PFO had greater mean modified RoPE score (4.0 vs. 3.3, p&lt;0.001). The area under the curve for the RoPE score in predicting PFO was 0.625 (95%CI 0.620-0.629). The best diagnostic power of the RoPE score was achieved with a cut point of ≥4 where the sensitivity was 55% and the specificity was 64.2%. A cut point of ≥5 increased specificity (83.1%) at the expense of sensitivity (35.8%). The strongest predictor of PFO was deep vein thrombosis (OR 3.97, 95%CI 3.76-4.20). Conclusions: The modified RoPE score had modest predictive value in identifying patients with PFO among patients admitted with AIS.

The COVID-19-medical emergency has ended worldwide, yet there is still a need to evaluate the psychological impact of these years of unprecedented changes on students’ life. Methods: This study aims to assess and compare COVID-19-related stressors (Relationships-and-Academic-Life; Isolation; Fear-of-Contagion) and psychophysical symptoms reported by university students in April-2020, April 2021, and April 2022. The predictive role of COVID-19-related stressors on psychophysical symptoms within each time was also tested. Data were collected among 637 university students in April-2020 (n = 197), April-2021 (n = 200), April-2022 (n = 240). Results: In April-2022, perceived Isolation and Fear-of-Contagion decreased from the peak registered in April-2021, but stress related to Relationships-and-Academic-Life remained noteworthy high. A sharp and ongoing increase in psychophysical symptoms was found, with more than 50% of students reporting clinical levels of Sleep-Disorders, Depression, Psychoticism, and Interpersonal-Sensitivity. In April-2022, students still perceiving stress related to Relationships-and-Academic-Life and Isolation were at risk for Anxiety, Somatization, and Sleep-Disorders, while those still perceiving stress related to Fear-of-Contagion were also at risk for Depression, Obsessive-Compulsive, and Psychoticism. Conclusion: Findings emphasized the long-lasting detrimental effects of the COVID-19-related stress. Interventions must pinpoint the complex post-pandemic adjustment process and their effects on university students' psychophysical health.

Lyme disease is a highly prevalent tick-borne infection caused by Borrelia burgdorferi spirochetes in North America and Eurasia. Diagnosis of the early disease remains difficult with the currently approved serological tests in the absence of noticeable tick bite or erythema migrans due to presentation of non-specific symptoms and the absence of antibodies early in infection. Furthermore, it is difficult to distinguish persistence of disease and reinfection in the endemic regions. If not treated early, infection spreads throughout the body and affects most organs with disease manifestations including arthritis, musculoskeletal pain, neuroborreliosis and acrodermatitis chronicum atrophicans. Although most patients recover after antibiotic treatment, ~10-12% of show recurrence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). Various causes of PTLDS are not well-defined; however, the spirochete persisters, antigenic debris, dysregulation of immunological response in individuals or a combination of these factors are proposed to result in continuation of Lyme disease manifestations. Based on these considerations, this review highlights currently employed treatment approaches with antimicrobials and vaccines being tried for prevention of B. burgdorferi infection. We also summarize combinatorial approaches that could be employed to alleviate symptoms to improve the quality of life of the individuals suffering from long Lyme disease.

Applying the iterative methodology for dimensionality reduction/feature selection using categorical gradient boosted trees, as it has been defined in and has been successfully applied on similar datasets in and , on a dataset consisted of 12708 gene expressions coming from 5052 individuals from 105 studies, we classify whether a person has acute myeloid leukaemia (AML) or is healthy. A CatBoost model on a dataset with reduced dimensions of 72 genes reached a ROC-AUC score of 0.9973 using ten fold cross validation (10CV) and ROC-AUC: 0.9988 on an inference dataset. We further investigate the options of using less genes that potentially could be used in clinical practise and genes than have not been associated to AML yet, or to blood cancer in general. On the same folds of the 10CV and on the same inference dataset the performance of the tuned CatBoost models show that it could be the case that not all genes with an association to AML have been found yet and 19 genes could be enough to predict AML: CatBoost63 (ROC-AUC: 0.9941, Test: 0.9942), CatBoost19: (ROC-AUC: 0.9946, Test: 0.9941) and CatBoost15: (ROC-AUC: 0.9922, Test: 0.9900). In addition, our results verify that a gene diagnostic test for AML could be possible in the future as well as further research is needed on these 15 genes that it could lead to new and better drugs.

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) and telomere length (TL)—in blood leukocytes, nasal cells (NC), and induced sputum (IS) one-year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data by questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male gender, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p&lt;0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p&lt;0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p≤0.05) and NC (p&lt;0.001), and were biologically older than COPD patients (p&lt;0.05). These findings suggest the need for monitoring aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

In the present study, we investigate the post-editese phenomenon, i.e., the unique features that set machine translated post-edited texts apart from human-translated texts. We use two literary texts, namely, the English children's novel by Lewis Carroll Alice’s Adventures in Wonderland (AW) and Paula Hawkins' popular book The Girl on the Train (TGOTT) translated from English into Brazilian-Portuguese to investigate whether the post-editese features can be found on the surface of the post-edited (PE) texts. In addition, we examine how the features found in the PE texts differ from the features encountered in the human-translated (HT) and machine translation (MT) versions of the same source text. Results revealed evidence for post-editese for TGOTT only with PE versions being more similar to the MT output than to the HT texts.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases

This article describes the POTENTIALS project, which aimed to develop business models for the reuse of former industrial and mining sites in different regions. The project focused on the creation of eco-industrial parks as a result to enable sustainable energy production and reduce waste and pollution. A key aspect was the Territorial Impact Assessment (TIA), a new and complex policy assessment tool. Therefore, the TEQUILA (Territorial Efficiency Quality and Identity Layer Assessment) approach is used to describe the TIA and emphasizes its application in assessing the impact of EU policies and projects on territorial cohesion. It underlines the need for a differentiated understanding of the regional characteristics and potential impacts of policies; and stresses the importance of regionalized impact models for the assessment. Furthermore, the process and results of applying the TEQUILA methodology to assess the territorial impact of different scenarios of business models within the POTENTIALS project is given.

Background: Boronic acids form di-ester bonds with cis-hydroxyl groups in carbohydrates. The formation of these adducts could impair the physical and chemical properties of the precursors, even their biological activity. Methods: Two carbohydrate-derivatives from D-fructose and D-arabinose and phenylboronic acid were synthesized in a straightforward one-step procedure and chemically characterized by spectroscopy and X-ray diffraction crystallography. Also, an acute toxicity test was performed to determine their Lethal Dose50 (LD50) by using the Lorke’s method. Results: Analytical chemistry assays confirmed adducts by the generation of the diester bonds with a β-D-pyranose of carbohydrates, including signals corresponding to the formation of new bonds, like the stretching of B-O bonds. The NMR spectra yielded information about the stereoselectivity in the synthesis reaction by the finding of just one signal in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests showed that LD50 value for both compounds is 1265 mg/kg, while Effective Dose 50 for sedation is 531 mg/kg. However, differences were in the onset and lapse of sedation. Conclusions: These adducts are bioactive and highly safe agents. Further biological evaluation is desirable to explore medical purposes.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

It is axiomatic to underscore that a well-managed education system is deemed globally as one of the crucial prerequisites for not only the growth and development of every society or geopolitical space but also one of the veritable hallmarks of a diversified and functional economy that will, in the long run, culminate in economic emancipation of the people. The education industry faces enormous challenges in several countries in Africa, and Nigeria is not an exception. Even though education remains the bedrock or superstructure on which other societal structures such as politics, culture, religion, economics, etc. are laid; it is quite disheartening that education in Nigeria is not effectively and efficiently managed for economic diversification and emancipation of the recipients of such education. Indeed, the industry faces innumerable challenges, especially in contemporary times than in the pre-colonial era when the education system was essentially functional. The hydra-headed nature of the challenges with Nigeria’s educational system has inevitably resulted in different dimensions of economic quagmires entangling the country and making most of its citizens find it extremely difficult to eke out and or survive. The level of dysfunctionalities in various sections of the education system has made it seemingly intractable to palliate the economic predicaments that have been confronting the country let alone emancipate it from the monoculture of its overdependence on oil. The author of this treatise is diagnostic in his approach to understanding the intricacies of the challenges that frontally battle the Nigerian education system and deprive it of being a veritable tool for a functional economy as well catalyst for the economic emancipation of its people. The paper, through the analyses of relevant literature, amplifies the conceptual and operational dimensions of the identified challenges, offers probable suggestions on the ways by which the challenges can be tackled and finally draws a conclusion.

Background. Moral distress (MD) and Burnout of Health Care Personnel (HCP) were extensively studied during the pandemic. However, little information is available about their prevalence after its decline. This study assesses the prevalence of MD, and burnout after the decline of the pandemic. Methods. The British Medical Association questionnaire referring to MD and the Maslach Burnout questionnaire were addressed to the hospital’s personnel. Results. 516 valid questionnaires were included in the study. Nurses’ participation rate was 67% and doctors 41%. MD was identical among doctors and nurses 73,8%, and in decremental order factors contributing to MD are insufficient staff, mental fatigue, and physical fatigue. Participants believe that more staff, less bureaucracy, and greater emotional support would alleviate MD. Doctors score higher than nurses for lack of time to give sufficient support to patients and public health decisions affecting communities. To alleviate MD, doctors ask for more ethical and legal support, more funding and working fewer hours. Nurses score high on emotional exhaustion and depersonalization. Conclusions. MD and burnout persist among HCP after the decline of the pandemic. Participants believe that institutional and public health decisions would help alleviate MD. Leaders and institutions must provide more supportive environments to moderate MD.

Background: Acute kidney injury (AKI) and contrast-induced nephropathy (CIN) are common complications following percutaneous coronary intervention (PCI) or coronary angiography (CAG), presenting significant clinical challenges. Machine learning (ML) models offer promise for improving patient outcomes through early detection and intervention strategies. Methods: A comprehensive literature search following PRISMA guidelines was conducted in PubMed, Scopus, and Embase from inception to June 11, 2024. Study characteristics, ML Models, performance metrics (AUC, accuracy, sensitivity, specificity, precision), and risk of bias assessment using the PROBAST tool were extracted. Statistical analysis used a random-effects model to pool AUC values, with heterogeneity assessed via the I² statistic. Results: From 431 initial studies, 14 met the inclusion criteria. Gradient Boosting Machine (GBM) and Support Vector Machine (SVM) models showed the highest pooled AUCs of 0.87 (95% CI: 0.82-0.92) and 0.85 (95% CI: 0.80-0.90), respectively, with low heterogeneity (I² < 30%). Random Forest (RF) had a similar AUC of 0.85 (95% CI: 0.78-0.92) but significant heterogeneity (I² > 90%). Multilayer Perceptron (MLP) and XGBoost models had moderate pooled AUCs of 0.79 (95% CI: 0.74-0.84) with high heterogeneity. RF showed strong accuracy (0.83, 95% CI: 0.70-0.96), while SVM had balanced sensitivity (0.69, 95% CI: 0.63-0.75) and specificity (0.73, 95% CI: 0.60-0.86). Age, serum creatinine, left ventricular ejection fraction, and hemoglobin consistently influenced model efficacy. Conclusions: GBM and SVM models, with robust AUCs and low heterogeneity, are effective in predicting AKI and CIN post-PCI/CAG. RF, MLP, and XGBoost, despite competitive AUCs, showed considerable heterogeneity, emphasizing the need for further validation.

Human bocavirus (HBoV) is an emerging virus that has been detected worldwide that could be associated with cases of acute gastroenteritis (AGE). However, its contribution to AGE has not been elucidated. This study aimed to describe the frequency, clinical features, and HBoV genotypes circulation in children up to 5 years with or without AGE symptoms in Acre, Northern Brazil. A total of 480 stool samples were collected between January and December 2012. Fecal samples were used for extraction, nested PCR amplification, and sequencing for genotyping. Statistical analysis was applied to verify the association between epidemiological and clinical characteristics. Overall HBoV-positivity was 10% (48/480), being HBoV-positivity rates of 8.4% (19/226) and 11.4% (29/254) recorded among diarrheic and non-diarrheic children, respectively. The most affected age group was between 7 and 24 months (50%). HBoV infection was more frequent in children living in urban areas (85.4%), using water from the public network (56.2%), and living with adequate sewage facilities (50%). Co-infection with other enteric viruses was 16.7% (8/48) and the most prevalent coinfection was RVA+ HBoV (50%, 4/8). HBoV‐1 was the most frequent species detected, responsible for 43.8% (21/48) of cases, followed by HBoV-3 (29.2%, 14/48) and HBoV-2 (25%, 12/48). In the present study, HBoV infections are not associated with AGE, as most HBoV cases belonged to the non-diarrheal group without AGE symptoms. Future studies are warranted to determine the role of HBoV in causing acute diarrhea disease.

C. auris is a newly emerging yeast, raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analysed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could be traced only in 10 patients, according to the epidemiological investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first case detected positive.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

(1) Background: Acute myocardial infarction in pregnancy (pAMI) is a rare event, often caused by non-classical factors rather than atherosclerosis. The management of such a complicationrequires a multidisciplinary team and it is important to bring together the specialities involved to ensure that these teams are coordinated and ready to respond. The management of pAMI poses unique challenges as it requires considering both maternal and fetal well-being. (2) Methods: We present the case of a 36-week pregnant woman who presented with antero-lateral ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock. To ensure comprehensive decision-making, an emergency Pregnancy Heart Team meeting was convened, comprising interventional cardi-ologists, gynecologists, and anesthesiologists. The team prioritized interventional treatment for pAMI, according to ESC guidelines, and opted for primary percutaneous coronary intervention (PCI) due to the unstable maternal condition.; (3) Results: The patient underwent primary PCI as the chosen intervention for pAMI. A rapid response gynecology team closely monitored the procedure and was prepared to intervene in case of irreversible hemodynamic compromise leading to cardiac arrest. An emergency caesarean section was deemed necessary if cardiac ac-tivity was not restored within 4 minutes.; (4) Conclusions: Managing pAMI requires a multidis-ciplinary approach that balances the maternal and fetal well-being. In this particular case, the Pregnancy Heart Team decided to prioritize interventional treatment with primary PCI due to the unstable maternal condition. The presence of a closely monitored gynecology team ensured prompt action in case of complications.

Background: This systematic review aims to investigate whether percutaneous transhepatic gallbladder drainage (PTGDB), as definitive treatment, is superior to emergency cholecystectomy (EC) in high-risk patients with acute cholecystitis (AC). Material and methods: A systematic literature search was performed until December 2022 using Scopus, Medline/PubMed and Web of Science databases in order to compare PTGDB as definitive treatment vs EC in AC. Results: Seventeen studies (1 Randomized Control Trials and 16 observational studies) have been included with a total of 783,672 patients (32,634 treated with PTGDB vs 4,663 who underwent laparoscopic cholecystectomy, 343 who underwent open cholecystectomy and 746,032 who underwent cholecystectomy, but without laparoscopic or open approach being specified). The quality assessment (ROBINS-I) of the not randomized studies showed a serious risk, differently the evaluation of the randomized study (RoB 2) showed a low risk of bias. Analysis of the results shows that PTGDB, despite being minimally invasive, do not have different incidence of complications than EC (RR 0.77 95% CI [0.44 to 1.34]; I2 = 99%; P=0.36). A lower postoperative mortality was reported in patients who underwent EC (2.37%) than in PTGDB group (13.78 %) (RR 4.21; 95% CI [2.69 to 6.58]; P < 0.00001), furthermore the risk of hospital readmission for biliary complications (RR 2.19 95% CI [1.72 to 2.79]; I2 = 48 %; P<0.00001) and hospital stay (MD 4.29 95% CI [2.40 to 6.19]; P<0.00001) were lower in EC group. Conclusions: No advantage in using PTGDB as a definitive treatment over EC in the management of critically ill patients with AC has been demonstrated; the results of our systematic review and meta-analysis suggest using EC as the treatment of first choice, even for very high-surgical-risk patient in which PTGDB should be reserved. The major limitation of this systematic review and meta-analysis is associated to a low quality of evidence for the serious bias in the not randomized studies. For this reason, new high powered and well-designed clinical trials are needed to recommend PTGDB as definitive treatment in patients unfit for surgery or those who refuse to undergo surgery.

Our understanding of Alzheimer’s disease (AD) pathogenesis has developed with several hypotheses over the last 40 years, including the Amyloid and Tau hypotheses, respectively. More recently, the p53 protein, well-known as ‘the guardian of the genome,’ has gained attention for its role in the early evolution of AD. This is due to p53’s central role in the control of oxidative stress and potential involvement in both Amyloid and Tau pathways. p53 is commonly regulated by post-translational modifications (PTMs), which affect its conformation, increasing its capacity to adopt multiple structural and functional states, including those that can influence several processes in AD. The following review will explore the impact of p53 post-translational modifications (PTMs) on its function and consequential involvement in AD pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

Objectives: Recently, desert dust in Europe has been recognized as a cardiovascular health problem. In Spain, desert dust inflows in recent years have been associated with worsening air quality. The present study examines whether desert dust events are related to the incidence of acute coronary syndrome (ACS) in patients under 55 years of age. Methods: Data from 2416 consecutive patients admitted to a tertiary hospital due to ACS were prospectively analyzed. A case-crossover time-stratified design using Poisson conditional regression models was applied to estimate the impact of desert dust events involving particulate matter concentrations of aerodynamic diameter < 10 μm (PM10) on the incidence of ACS. Results: Desert dust intrusion on days 0 to 5 after ACS onset showed no significant association with the incidence of ACS in patients under 55 years of age. The incidence rate ratios of PM10 concentrations 1, 2, 3, 3, 4 and 5 days before ACS onset (for changes of 10 µg/m3) were 1.02 (95% CI 0.97-1.1; p = 0.41), 1.01 (95% CI 0.96-1.07; p = 0.66), 0.99 (95% CI 0.94-1.05; p = 0.78), 0.96 (95% CI 0.9-1.02; p = 0.18) and 0.97 (95% CI 0.91-1.04; p = 0.41). Conclusions: Our findings suggest that desert dust is unlikely to be related to the incidence of premature coronary heart disease.

Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

Background: This study aimed to present the development process and characteristics of the Korean Registry of Acute Myocardial Infarction for Regional Cardiocerebrovascular Centers (KRAMI-RCC). Methods: We developed KRAMI-RCC, a web-based registry for patients with AMI. Patients from 14 RCCs were registered for more than 3 years from July 2016. It includes an automatic error-checking system, and user training and on-site monitoring are performed to manage data quality. Results: A total of 11,700 AMI patients were registered in KRAMI-RCC over 3 years (73.9% men). The proportions of patients with ST-elevation and non-ST-elevation myocardial infarction at discharge were 43.4% and 56.6%, respectively. Of the total 3-year patients, 5.6% died in the hospital and 4.4% died 12 months after discharge. The case fatality within 12 months was 9.7%. Prehospital care data showed delayed arrival time after onset of symptoms (median 153 min) and low transportation rate by public ambulance (25.2%). Post-hospital care data showed lower participation rate in the second rehabilitation program (16.8%). Conclusions: The recently developed KRAMI-RCC registry has been more focused on pre-hospital and post-hospital data, which will be helpful in understanding the current state of AMI disease management and in making policy decisions to reduce case fatality in Korea.

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during pre-conception, pregnancy and throughout life have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing, but remains unexplained. Advances in genomic profiling, including genome‐wide gene expression, DNA copy number, and single nucleotide polymorphism [SNP] genotype may shed some light on the role of genetics in these disparities. Separate two-hit hypothesis for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in occurrence of leukemia requires further investigations. This review summarizes some of the above factors and the direction for future research on the etiology of acute leukemias.

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evalua-tion. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP, as-sessing its accuracy, timing, safety, and future technological improvement. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a cru-cial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visu-alization of the pancreas, biliary system, and adjacent structures. High accuracy of EUS is evident in detecting the actual causes of IAP such as microlithiasis, small bile duct stones, pancreas divisum, and small pancreatic tumors. Optimal timing for EUS is post-resolution of the acute phase of the disease. EUS, when conducted by experienced endoscopists, it boasts minimal safety concerns, and is crucial to prevent complications. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in cytological analy-sis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicenter prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.

The simplified, combined protocol admits children with a mid-upper-arm circumference (MUAC) of <125 mm or edema to malnutrition treatment with ready-to-use therapeutic food (RUTF) prescribing 2 daily RUTF sachets to children with MUAC <115 mm or edema and 1 daily sachet to those with MUAC ≥115 mm but <125 mm. This treatment has previously been shown to result in non-inferior programmatic outcomes compared to standard treatment. We aimed at observing its effectiveness in a routine setting at scale, including via delivery by community health workers (CHW). A total of 27 601 children were admitted to the simplified, combined treatment. Treatment resulted in 96% overall recovery with a mean LOS of 40 days and a mean RUTF consumption of 63 sachets per child treated. Among children admitted with MUAC <115 mm or edema 94% recovered with a mean LOS of 55 days and consuming an average of 97 RUTF sachets. Recovery in all sub-groups studied exceeded 90%.Treatment by CHWs resulted in similar (96%) recovery as treatment by formal health care workers (96%). The simplified, combined protocol results in high recovery and low RUTF consumption per child treated, and can safely be adopted by CHWs to provide treatment in the community-level.

Ankle sprains are the most frequently occurring musculoskeletal injuries among recreational athletes. Ankle support through bandages following the initial orthotic treatment might be beneficial for rehabilitation purposes. Since hardly any study has investigated the impact of bandages in the acute phase of ankle sprains, our study examined the immediate effects of wearing an ankle bandage on fine coordination, proprioception, and motor performance in subjects five weeks after an acute ankle injury. In total, 70 subjects with acute unilateral supination trauma were tested. All subjects completed several rating questionnaires and biomechanical investigations, including a fine coordination and proprioception test, single leg stances, the Y-Balance test and gait analysis. All biomechanical investigations were conducted for the subject's injured leg with and without a bandage (MalleoTrain® Bauerfeind AG) and the healthy leg. Subjects reported moderate to strong improvements in ankle stability and pain when wearing the bandage. Wearing the bandage significantly normalized subjects’ single leg stance performance, as well as the stance phase duration, and the vertical ground reaction forces during walking. However, the bandage did not have a clear effect on fine coordination and proprioception. Wearing a bandage in the acute phase of an ankle sprain may immediately improve motor performance, including standing and walking.

Biochirality is evident in the hierarchical relation of molecular and cellular physiology during organism development and aging. Chirality influences the higher levels of biological processes, such as perception, memory and cognition, through intermolecular interactions between DNA, proteins, and lipids. At the molecular level, an organism's aging is the accumulation of macro-molecules with the aberrant composition, chirality, and folding. Cellular aging is driven by the non-physiological phase transitions (PhTs) withing membrane-bound and membrane-less compartments. Genomic instability and protein aging, as the interconnected root-causes of cell and organism aging, share two essential feature – spontaneous nature and accumulation over a lifetime. Consequently, we will analyze the interaction between the enzymatic (Enz) and spontaneous (Sp) post-translational modifications (PTMs^Enz and PTMs ^Sp). Both forms of PTMs significantly contribute to the balance of L- and D-amino acids (L/D-AAs) in organisms, modulating the functions of nervous and immune systems. The most abundant form of PTM - enzymatic phosphorylation is bio-chemically associated with the spontaneous racemization (Rz^Sp). The crass talk of enzymatic phosphorylation and spontaneous racemization, as an essential determinant of protein aging and aggregation, associated with the aberrant autophagy, apoptosis, and cell signaling, is discussed in this review.

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI+Veh (infarcted, treated with vehicle); and AMI+PY (infarcted, treated with the cholinesterase inhibitor pyridostigmine bromide (PY) - 40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. Clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI+PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI+Veh group. Furthermore, there was a notable downregulation of pro-inflammatory gene expression and an upregulation of anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers indicative of subclinical kidney injury. Conclusion: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic in 2020, following which a global genetic vaccination program has been rapidly implemented as a fundamental solution. However, it has been reported worldwide that the modified mRNAs encoding spike proteins and lipid nanoparticles, which are used as drug delivery systems, not only cause thrombosis and cardiovascular disorders post vaccination, but might also cause diverse diseases involving all organs and systems, including the nervous system. Furthermore, the toxicity and pathogenicity of spike proteins may necessitate defining these proteins as nonbiological infective material. Based on these reports and the abundant evidence that has come to light in the past few years, this paper aims to draw the attention of medical professionals to the various risks associated with transfusion using blood products derived from long COVID patients or from genetic vaccine recipients, and to make proposals regarding specific inspection items, testing methods, regulations, etc. This paper provides insights to address the post-vaccination syndrome and its consequences following such genetic vaccination programs.

INTRODUCTION Recently there has been a significant increase in age in the United States. It is necessary to better understand the physiological and surgical needs of these patients in order to optimize outcomes. The vast majority of procedures performed in adult patients are low-risk operations, such as laparoscopic cholecystectomy. Our aim is to investigate the outcomes, including length of stay, morbidity, mortality, re-admission and discharge disposition of the elderly population (>80) undergoing low-risk operations in our tertiary community hospital. METHODS A retrospective chart review was done at a tertiary community hospital. The time frame utilized was 2011-2015. Patients were excluded only on the basis of their age (< 80) at the time of operation. RESULTS There were a total of 30 patients who underwent laparoscopic cholecystectomy from 2011 to 2015. 21 patients (70%) were female and 9 (30%) were male. No patients were converted to an open procedure. The average age was 86.4 years and average ASA classification prior to surgery was 2.88. Higher ASA class, specifically those that were class III/IV were more likely to have an increased length of stay that was statistically significant. Overall age greater than 80 was an independent risk factor for transfer to a higher level of care upon discharge (SNF, LTAC, etc.), a surrogate marker for physical decompensation following surgery. CONCLUSIONS Routine surgery, such as the laparoscopic cholecystectomy, effects the elderly population in a more substantial way, and early recognition coupled with increased education for physicians regarding geriatric patients can help to reduce length of stay, morbidity, and overall physical and mental deconditioning.

Abstract Objectives To assess the causes and risk factors of posttraumatic stress disorder (PTSD) in adult asylum seekers and refugees. To explore whether the causes and risk factors of PTSD, between male and female adult refugees/ asylum seekers is different. Study design Systematic review of current literature. Data Sources PubMed, Web of Science, Scopus and Google Scholar up until February 2019 Method A structured systematic search was conducted in the relevant databases. Papers were excluded, if they failed to meet the inclusion and exclusion criteria. Afterwards, a qualitative assessment was performed on the selected papers. Results 12 Studies were included for the final analysis. All papers were either case studies/report or cross sectional studies. The number of traumatic events experienced by refugees/asylum seekers, is the most frequently reported pre-migration causes for PTSD development. Whilst acculturative stress, is the most common post migration stressor. There were mixed reports, regarding the causes of PTSD between both genders of refugees/asylum seekers. Conclusion This reviews’ findings, have potential clinical application into helping clinicians, to risk stratify refugees/asylum seekers for PTSD development and thus aid in embarking on earlier intervention measures. However, more rigorous research similar to this one, is needed for it to be implemented into clinical practice.

Background： Sepsis-induced acute lung injury (ALI) is characterized by disruption of the epithelial barrier and activation of alveolar macrophages (AMs), which leads to uncontrolled pulmonary inflammation. However, effective treatments for ALI are unavailable. This study aimed to discover potential diagnostic molecular biomarkers based on bioinformatics, which will benefit the diagnosis and treatment of sepsis-induced ALI. Methods: GSE10474 was analyzed for differentially expressed genes (DEGs) in sepsis patients with ALI (sepsis + ALI) compared with sepsis patients without ALI. Functional enrichment analysis and protein-protein interaction (PPI) network were performed. on the DEGs via R package “clusterProfiler”, and visualized via Cytoscape. Prediction analysis of microarrays (PAM) was performed to identify diagnostic biomarkers and the diagnostic ability of diagnostic biomarkers was accessed via receiver operating characteristic (ROC) curves. Moreover, interactions among diagnostic biomarkers were analyzed via GeneMANIA. We also analyzed the function of diagnostic biomarkers and predicted their corresponding drugs via Cytoscape plugin BiNGO and web tool DGIdb. At last, we analyzed the transcriptional regulation of the diagnostic biomarkers via the web tool miRNet. Results: 71 genes were found to be differentially expressed in the sepsis + ALI group, mainly involved in immune-related biological processes and pathways. STRING database indicated 31 DEGs have protein-protein interactions. In addition, the PAM identified 6 diagnostic biomarkers, including HIST1H4H, CDKN1A, HMOX1, NQO2, RHOB, and TREM1, from these 31 DEGs. Conclusion: In conclusion, through bioinformatics analyses, we identified 6 potential diagnostic biomarkers and targets for sepsis-induced ALI.

Current study was to estimation the post-harvest loss of avocado at the producer level using cross-sectional data obtained from 385 proportionately sampled respondents from Wolaita and Kembata Tembaro Zones, the SNNPR of Ethiopia. Descriptive and multiple regression analysis were used to the amount and determinant of post harvest loss of avocado fruits. Estimated total post harvest- loss of avocados was 24%; of which 5.7% unacceptable harvesting methods and 4.9% of improper storage practices. The respondent's sex, education, income, training, contact with extension agents, distance from the nearest road, and off-farm income were found to be negative determinants, whereas storage accessibility and avocado harvest techniques were found to be positive determinants of post-harvest loss of avocado fruits. Post-harvest management techniques for avocados need to be better understood and used by avocado growers if they are to minimize losses. Post-harvest losses contribute considerably to food insecurity and create a problem for the source of revenue for people and the economy of the country as well. Therefore, the use of a practical and effective post-harvest loss reduction technique could be a sustainable solution to increase food availability, eliminate hunger and improve farmers' livelihoods.

Background: The assessment of the incidence and characteristic of acute and chronic post-operative endophthalmitis (POE) after cataract surgery in Poland during 2010 - 2015. Patients and methods: All hospitalizations of patients, in the National Database of Hospitalizations, who underwent cataract surgery alone or in combined procedures in Poland between January 2010 and December 2015, with a billing code of endophthalmitis, were selected. Acute endophthalmitis was identified if symptoms occurred within 1 - 42 days from the cataract surgery and chronic endophthalmitis if symptoms occurred ≥ 43 days after cataract surgery, respectively. Results: In total, 1331 cases of POE after 1,218,777 cataract extractions were identified. The overall incidence of POE decreased from 0.125% in 2010 to 0.066% in 2015. In multiple logistic regression analyses, increasing age was significantly associated with acute POE, while type II diabetes mellitus, extracapsular cataract extraction and one-day surgery were significantly associated with chronic POE. The combined cataract surgery and male sex were significant risk factors for both acute and chronic POE. A total of 62.51% of all eyes affected by POE received antibiotic treatment and 37.49% had vitrectomy treatment. Conclusions: During the study period, the total incidence of post-operative endophthalmitis after cataract surgery decreased significantly.

Abstract: Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully un-derstood and causal treatment options are not available. Recently we demonstrated that Hepa-ranase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that As-pirin has inhibitory effect on Hpa. Another compound, which possesses a mild pan-creato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesize that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhib-itors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in ex-perimental model of AP induced by Cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the se-rum levels of Lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in heparanase transgenic (Hpa-Tg) mice vs wild-type (WT) mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

Aortic dissection is a clinicopathological entity caused by rupture of the intima leading to a high mortality if not treated. Over time, diagnostic and investigative methods, antihypertensive therapy, and early referrals have resulted in improving outcomes according to registry data. Some data has also emerged from recent studies suggesting a link between Human Cytomegalovirus (HCMV) infection and aortic dissection. Furthermore, the use of microRNAs have also become increasingly widespread in the literature. These have been noted to play a role in aortic dissections with elevated levels noted in studies as early as 2017. This review aims to provide a broad and holistic overview of the role of miRNAs, while studying the role of HCMV infection in the context of aortic dissections. The role of long non-coding RNAs, circular RNAs and microRNAs are explored to identify changes in expression during aortic dissections. The use of such biomarkers may one day be translated into clinical practice to allow early detection and prognostication of outcomes and drive preventative and therapeutic options in the future.

There are presently more than 18 known aflatoxins (>18) most of which have been insufficiently studied for their incidence, health-risk, and mechanisms of toxicity to allow effective intervention and control means that would significantly and sustainably reduce their incidence and adverse effects on health and economy. Among these, aflatoxin B1 (AFB1) has by far been the most studied; and yet, many aspects of the range and mechanisms of the diseases it causes remain to be elucidated. Its mutagenicity, tumorigenicity, and carcinogenicity, which are the best known still suffer from many limitations regarding the relative contribution of the oxidative stress and the reactive epoxide derivative (Aflatoxin-exo 8,9-epoxide) in the induction of the diseases, as well as its metabolic and synthesis pathways. Additionally, despite the well-established additive effects for carcinogenicity between AFB1 and other risk factors, e.g., hepatitis viruses B and C, and the algal hepatotoxic microcystins, the mechanisms of this synergy remain unclear. This study reviews the most recent advances in the mechanisms of toxicity of aflatoxins and the adverse health effects that they cause in humans and animals.

Acute myeloid leukemia (AML) remains a challenging hematologic malignancy. The presence of TP53 mutations in AML poses a therapeutic challenge, considering that standard treatments face significant setbacks in achieving meaningful responses. There is a pressing need for the development of innovative treatment modalities to overcome resistance to conventional treatments attributable to the unique biology of TP53-mutated (TP53mut) AML. This review underscores the role of TP53 mutations in AML, examines the current landscape of treatment options, and highlights novel therapeutic approaches, including targeted therapies, combination regimens, and emerging immunotherapies as well as agents being explored in preclinical studies, for their potential to address the unique hurdles posed by TP53mut AML.

Natural products from medicinal plants, either as pure compounds or as standardized extracts, provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. The objects of the study are medicinal plant raw materials Saussurea sordida Kar&Kir and Saussurea alpina DC. collected from South Kazakhstan during the flowering period in the spring-summer months of 2021. The present study was aimed to investigate the toxic effects acute administration of ethanol extracts from plants S. sordida and S. alpina in male Wistar rats. The ethanol extract by subjected to Phytochemical Screening, Fourier transform infrared spec-troscopy (FTIR) analysis. Phytochemical screening of the extract revealed the presence of phenolic compounds. FT-IR spectroscopic analysis revealed various characteristic band values with various functional groups in the formulation extract such as amines, alcohol, phenol, alkane, alkene, and conjugated acid groups. FT-IR analysis of peak values with various functional compounds such as alcohols, phenols, carboxylic acids, aldehydes, amides, amino acids, anhydrides, esters, ketones, unsaturated aliphatic, aromatics, unsaturated heterocycles, amines, nitro compound, alkanes, al-kenes and sugars. Histological examination of organ samples after studying the chronic toxicity of ex-tracts of two plant species (S. sordida . and S. alpina) revealed no pathological changes. The acute toxicity study revealed no lethal effects and behavioral signs of toxicity at the tested doses indicating that LD50 is greater than 2000 mg/kg. These results show low toxicity of on short-term use and liver toxicity on long-term use. This study helps to predict the formula and structure of active molecules which can be used as medicinal drugs. This result also enhances the traditional usage of S. sordida and S. alpina , which possesses a number of bioactive compounds.

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but literature on long-term recovery of young adults after mild-to-moderate infection is lacking. Heart rate variability (HRV) allows observation of autonomic nervous system (ANS) modulation post SARS-CoV-2 infection. Additionally, physical activity (PA) helps improve ANS modulation, where investigation of PA influence on ANS recovery is vital to reduce risk and severity of symptoms. Clinicians may use this research to aid development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general amnamnesis was performed, followed by HRV and PA assessment. 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (2 doses) and assessments were repeated. Over the follow-up period, decrease in sympathetic (SNS) activity (mean heart rate: p=0.0024, CI=-24.67- -3.26; SNS index: p=0.0068, CI=-2.50- -0.32) and increase in parasympathetic (PNS) activity (mean RR:p=0.0097, CI=33.72-225.51; PNS index: p=0.0091, CI=-0.20-1.47) were observed. At follow-up, HRV was not different between groups (p>0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.

This case report describes a 71-year-old female with multiple comorbidities who presented with symptoms suggestive of stroke and was subsequently found to have severe acute kidney injury (AKI) due to acute interstitial nephritis (AIN). The patient has normal kidney function at baseline. She has been on hydrochlorothiazide and metoprolol succinate for hypertension for several years. Due to severe acute kidney injury, a kidney biopsy was performed, revealing severe Acute Interstitial Nephritis secondary and multiple intratubular oxalate crystals. The patient's renal function improved after withdrawing HCTZ, volume repletion and initiating prolonged prednisone taper. We attempt to provide some insights through our paper into the mechanism of acute renal failure from crystal nephropathy and its management.

The universal chirality is the commonly accepted view of nature. Biological chirality is the distinct part of the more general phenomena. Following this view, all living organisms are characterized by the non-equilibrium state of their molecular constituents. From the thermodynamic perspective, the non-equilibrium state of biomolecular ensemble holds inevitable consequences being the substrate of spontaneous reactions directed to equilibrium (not associated with life) state. At the protein level, spontaneous biological reactions represent the natural part of proteins' post-translational modifications (PTMs). The essential contribution to the origin and maintenance of the non-equilibrium state belongs to prevalent bio-molecular chirality. Correspondently, spontaneous PTMs such as racemization and glycation, working against life-supporting prevalent chirality, are known as the significant determinants of protein misfolding, dysfunctions, and aggregation. Accumulation of aberrant protein during life-span allows consideration of time-dependent spontaneous racemization and glycation as protein aging. Spontaneous PTMs of proteins is occurring in the interaction with other forms of enzymatic and non-enzymatic PTMs. In this review, we are considering the contribution of spontaneous racemization and non-enzymatic glycosylation to protein aging.

The purpose of this study was to analyze the influence of Chitosan 0.2% in various final cleaning methods on the bond strength of fiberglass post (FP) to intrarradicular dentin. Ninety bovine incisors were sectioned to obtain root remnants measuring 18 mm in length. The roots were divided: G1: EDTA 17%; G2: EDTA 17% + PUI; G3: EDTA 17% + EA; G4: EDTA 17% + XPF; G5: Chitosan 2%; G6: Chitosan 2% + PUI; G7: Chitosan 2% + EA; G8: Chitosan 2% +XPF. After carrying out the cleaning methods, the posts were installed, and the root cleaved to to generate two disks from each root third. Bond strength values (MPa) obtained from the micro push-out test data were assessed by Kruskal-Wallis and Dwass-Steel-Critchlow-Fligner tests for multiple comparisons (α = 5%). Differences were observed in the cervical third between G1 and G8 (p=0.038), G4 and G8 (p=0.003), G6 and G8 (p=0.049), and Control and G8 (p=0.019). The final cleaning method influenced the adhesion strength of cemented FP to intrarradicular dentin. Chitosan 0.2% + XPF positively influenced adhesion strength, with the highest values in the cervical third.

Premortem clinical diagnoses and postmortem autopsy findings do not match throughout history. These clinicopathological discrepancies are expected to be raised during the coronavirus disease 2019 (COVID-19) pandemic due to increased pressure on healthcare. At the same time, autopsies and clinicopathological discrepancies accurately display the quality of the healthcare system. To assess that, we examined the relevant works of literature according to the PRISMA-based protocol. As discrepancy rate changes in the correlation to the length of stay in the hospital, we also checked whether studies with patients from the intensive care unit (ICU) differed in discrepancies significantly. We found overall risk differences pretty much alike in "pre-COVID" and "during the pandemic" groups of studies. Based on that, we concluded that healthcare quality did not drop significantly during the pandemic. Be it as it may, the pandemic exposed some shortcomings in mortem healthcare regarding consensus to the autopsy, organ retention, burial, and the postponed burial or the digitalization of post mortem healthcare. All of these issues should be addressed in the future.

The embryonic epicardium originates from the proepicardium, an extracardiac primordium constituted by a cluster of mesothelial cells. In early embryos, the embryonic epicardium is characterized by a squamous cell epithelium resting on the myocardium surface. Subsequently, it invades the subepicardial space and thereafter the embryonic myocardium by means of epithelial-mesenchymal transition. Within the myocardium, epicardial-derived cells present multilineage potential, later differentiating into smooth muscle cells and contributing both to coronary vasculature and cardiac fibroblasts in the mature heart. Over the last decades, we have progressively increased our understanding of those cellular and molecular mechanisms driving proepicardial/embryonic epicardium formation. This study provides a state-of-the-art review of the transcriptional and emerging post-transcriptional mechanisms involved in the formation and differentiation of the embryonic epicardium.

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

The study evaluates the toxic effects of acute and sub-acute oral administration of methanol extracts of Geophila obvallata in rats. During acute study, a dose of 1600, 2900 and 5000 mg/kg bw of extract was orally administered to rats. Rats were observed for signs of toxicity for two weeks. During sub-acute study (28 days), the extract, at doses of 100, 500 and 1000 mg/kg bw were administered orally to rats while control rats were given only tap water. At the end of the study, samples were collected for analyses. In acute toxicity studies, the extract did not induce death after single dose administration. Hence, the LD50 was estimated above 5000mg/kg. The results of sub-acute toxicity study show that no significant changes were observed in the body weights, organ weights, kidney function and organ histology. There were significant changes in hematology and biochemical indices investigated at elevated doses of 500 and 1000 mg/kg bw compared to the control. GOE may be considered non-toxic at a dose of 100 mg/kg with promising applications in drug therapy.

The hematopoietic transcription factor Ikaros (IKZF1) regulates normal B cell development and functions as a tumor suppressor in precursor B cell acute lymphoblastic leukemia (B-ALL). MicroRNAs (miRNAs) are small regulatory RNAs that through post-transcriptional gene regulation play critical roles in intracellular processes including cell growth in cancer. However, the role of Ikaros in the regulation of miRNA expression in developing B cells is unknown. In this study, we examined the Ikaros-regulated miRNA targets using patient-derived IKZF1-mutated B-ALL xenograft-derived cell lines. Inducible expression of wild-type Ikaros (the Ik1 isoform) caused B-ALL growth arrest and exit from the cell cycle. Global miRNA expression analysis revealed a total of 31 miRNAs regulated by IK1, and ChIP-seq analysis showed that Ikaros bound to several Ik1-responsive miRNA genes. Examination of the prognostic significance of miRNA expression in B-ALL indicate that the IK1-regulated miRNAs hsa-miR-26b, hsa-miR-130b and hsa-miR-4649 are significantly associated with outcome in B-ALL. Our findings establish a potential regulatory circuit between the tumor-suppressor Ikaros and the oncogenic miRNA networks in IKZF1-mutated B-ALL. These results indicate that Ikaros regulates the expression of a subset of miRNAs, of which several may contribute to B-ALL growth.

Background Research in the subject of the influence of SARS-CoV-2 mechanisms on human’s homeostasis remains actual problem. Particular interest is the study of pathomorphological changes in the appendix in children with COVID-19. Objectives Aim of the study: morphological and molecular biological evaluation of the appendix in children of different age groups with COVID-19. Methods Groups were formed on the basis of anamnestic, clinical and morphological data: I (n = 42; aged 2 to 18 years, average - 10.8 years) – with an established clinical diagnosis: coronavirus infection (COVID-19; PCR+); II (n = 55; aged 2 to 18 years, average - 9.7 years) – with a confirmed clinical diagnosis of acute appendicitis; collected before the onset of the COVID-19 pandemic in 2017-2019; III (n = 38; aged 2 to 18 years, average - 10.3 years) - control group. Histological and immunohistochemical studies were conducted using primary antibodies to CD3, CD4, CD68, CD163, CD20, CD138 and to pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Results In most samples of appendix in children with COVID-19 were discovered signs of destructive phlegmonous-ulcerative and gangrenous appendicitis. An increase in CD3+, CD4+, CD68+, CD163+, CD20+ CD138+ immunocompetent cells was found in the appendix of children with COVID-19. As well, there is an increase in pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Conclusions The aforementioned pathological and immunohistochemical changes were more pronounced in the group of children aged 6-12 years (childhood).

In this work, we tried to emphasize whole transcriptome expression changes in the Wistar rats brainstem two hours after acute stress. Most of the genes were upregulated. We detected massive shift of neuropeptides Crh, Trh,Cga, Tshb, Uts2b, Tac4, Lep and neuropeptide receptors Hcrtr1, Sstr5, Bdkrb2, Crhr2 signaling, as well as Glutamate Grin3b, Grm2 and GABA Gpr156, Acetylcholine Chrm4,Chrne, Adreno- Adra2b receptors expression uprising. Intensive increase in expression of intermediate filaments Krt83/Krt86/Krt80/Krt84/Krt87/Krt4/Krt76 and motor proteins Myo7a, Klc3 was detected. Remarkably, at this time we also observed signs of microglia activation. Both expression of anti-inflammatory cytokines Il13, Ccl24 and proinflammatory cytokin’s receptors Il9r, Il12rb1, Tnfrsf14, Tnfrsf13c, Tnfrsf25, Tnfrsf1b were increased. In the Wnt signaling pathway, we have seen increased expression of ligands-receptors Wnt1, Wnt11, Ror2, and also negative regulators Notum, Sfrp5, Sost. Also we conducted cDNA libraries normalization with duplex specific nuclease and compared results. On the basis of our RNAseq data, we chose reference genes for RT-qPCR best suitable for experiments with acute stress.

The definition of Early Cholecystectomy (EC) is still debatable. This paper aims to find whether the timing of EC affects outcomes. This is a multicentric prospective observational study including patients with acute calculous cholecystitis (ACC) who had cholecystectomy within ten days from the onset of symptoms. Kruskall-Wallis test, Fisher’s Exact test and Spearman rank correlation were used for statistical analysis. The patients were divided into three groups depending on the timing of the operation: 0-3 days, 4-7 days, or 8-10 days from the onset of symptoms. 1117 patients were studied over a year. The time from the onset of symptoms to EC did not affect the postoperative complications and mortality, the conversion and the reintervention rate. It was a significant risk factor for intraoperative complications (0-3 days, 2.8%; 4-7 days, 5.6%; 8-10 days, 7.9%; p=0.01) and subtotal cholecystectomies (0-3 days, 2.7%; 4-7 days, 5.6%; 8-10 days, 10.9%; p&lt;0.001). ACC is an evolutive inflammatory process and, as the days go by, the local and systemic inflammation increases which makes surgery more complex and difficult with higher risk of intraoperative complications. We recommend performing EC for ACC as soon as possible within the first ten days of the onset of symptoms.

Residential satisfaction with post-disaster housing is crucial for the success and sustainability of a resettlement project. However, little attention has been given to this aspect in the permanent houses developed after the 2015 Gorkha earthquake. To bridge this gap, the study examined factors affecting residential satisfaction among poor displaced households resettled in the Panipokhari Integrated Settlement of Nepal. Data were collected through a questionnaire survey, interviews, and field observation. Internal consistency and reliability were assessed using Cronbach's Alpha test, while satisfaction was measured by mean satisfaction scores. The relative importance index ranked the factors, and Spearman's rank correlation coefficient analyzed their relationship with overall residential satisfaction. The study identified several crucial fac-tors influencing residential satisfaction, including the design and layout of the house, space for modification, provision of a kitchen garden and cattle shed, thermal comfort, completeness of the house, provision of a hearth, and spaces for rituals and cultural events. These findings shed light on the resettlement decisions of affected populations and provide valuable insights for policymakers, implementers, and researchers aiming for successful and sustainable resettlement outcomes.

Background: Paracetamol may be use as antipyretic agent for the treatment of fever, as well as an analgesic in the treatment of mild to moderate pain on post vaccination in infants. The use of Paracetamol during fever may be or may not be recommended since it may alter natural human body immune response although it may reduce pain. Objectives: This study described the relevancy of Paracetamol use post infants vaccination based on data collection systematic review analyses. This study aims to describe the effectiveness of breastfeeding in reducing pain and Paracetamol in reducing fever and pain post infants vaccination. Data Sources and Study Selection: Electronic literature search by hand searching six (6) databases which include Ovid LWW Total Access Collection and Medline, CINAHL (Cumulative Index to Nursing and Alled Health Literature) Plus with Fulltext, Science Direct, Proquest Dissertations and Theses, Proquest Education Journal and Proquest Health and Medical Complete. Additionally, manual reference checks of all articles on Paracetamol and breastfeeding post infants vaccination published in English Language between 1978 and 2017. Two level of screening were used on 9614 citations which include screening of abstracts and titles followed by full text screening. Data Synthesis: Data synthesis were tabulated into study characteristics, quality and effects. Authors of trials were not contacted for further details or provision of original data if the published report contained insufficient information. The study findings, as reported by the authors, were included in this review. The data in this research cannot be pool due to not enough data regarding odd ratio or relative risk as well as confidence interval in each study. Results: Systematic review of breastfeeding included three (3) studies from 9614 of database searching. The reviews of all these three (3) studies found significant benefit from breastfed in pain score and duration of crying as well as behavioral changes. None study stated the unbeneficial of breastfeeding before, during and after immunization. Meanwhile, systematic review of Paracetamol effectiveness included four (4) studies from 1177 of database searching. The reviews of two (2) studies found significant benefit from prophylaxis Paracetamol in fever and only one (1) study found significant benefit from prophylaxis Paracetamol in fussiness. On the other hand, there was one (1) study found not signifiant benefit from prophylaxis Paracetamol in fever. Other than that, there were two (2) studies evaluate the safety of prophylactic Paracetamol which revealed different outcomes, in which study by Prymula et. al. in 2009 found that antibody responses to several antigens were reduced significantly, and the other study by Uhari et. al. in 1988 found that antibody titres to DTP bacteria of placebo and PCM not differ significantly. Thus, Paracetamol seems to be not relevant post infants vaccination and breastfeeding was found to be beneficial post infants vaccination. Conclusions: The relevancy of giving Paracetamol post all types of vaccination may be questionable since the safety issue of this intervention may be arised. Breastfeeding before, during and after immunization are recommended for pain reduction as it was proved effectively. Finally, in deciding Paracetamol to be of rational use following infants immunization, it may need for further research which include in depth quantitative and qualitative studies to identify specific problem and causes regarding this issue.

Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies have been predominantly focused on DNA methylation, histone modifications and chromatin remodelling. However, recently, RNA modification (m6A-methylation) also termed ‘epitranscriptomics’ has emerged as a new layer of epigenetic regulation due to its diverse role in various biological processes. In this review, we have summarized the therapeutic potential of m6A-modifiers in controlling haematological disorders especially acute myeloid leukemia (AML). It is a type of blood cancer affecting specific subsets of blood-forming hematopoietic stem/progenitor cells (HSPCs) which proliferate rapidly and acquire self-renewable capacities with impaired terminal cell-differentiation and apoptosis leading to abnormal accumulation of white blood cells, and thus an alternative therapeutic approach is required urgently. Here, we have described how RNA m6A-modification machineries EEE (Editor/writer: Mettl3, Mettl14; Eraser/remover: FTO, ALKBH5 and Effector/reader: YTHDF-1/2) could be reformed into potential druggable candidate or as RNA modifying drug (RMD) to treat leukemia. Moreover, we have shed-light on the role of microRNA and suppressor of cytokine signalling (SOCS/CISH) in increasing anti-tumor immunity towards leukemia. We anticipate, our investigation will provide a fundamental knowledge in nurturing the potential of RNA modifiers in discovering novel therapeutics or immunotherapeutic procedures.

Introduction: Decompensated heart failure (HF) is a complex and debilitating syndrome, which constitutes a severe emergency condition with high morbidity and mortality. The kidneys play fundamental roles in the pathophysiology of HF and, in the context of decompensations, acute kidney injury (AKI) has a bilateral cause-and-effect relationship, which can significantly worsen prognosis. However, the interaction between AKI and decompensated HF is poorly understood. Objective: This study aimed to assess the occurrence of AKI in patients hospitalized due to decompensated HF and to analyze its prognostic impact during hospitalization. Methods: Prospective single-center observational study that included patients hospitalized due to decompensated HF in a tertiary-level teaching hospital, conducted between July 2017 and January 2020. Patients who developed AKI during hospitalization were compared with those who did not develop it, until hospital discharge or death. AKI was defined as a serum creatinine increase greater than or equal to 0.3 mg/dl in 48 hours, a 1.5-fold increase in baseline creatinine in seven days or urinary volume <0.5 ml/kg/h during six hours, according to the Acute Kidney Injury Network (AKIN) criteria. The endpoints analyzed were death, need for invasive mechanical ventilation (IMV) and length of hospital stay. The Wilcoxon, Mann-Whitney and unpaired student t tests were used. Results: Ninety-nine patients were included, with a mean age of 65.4 ± 14 years, of which 47 (47.5%) were male and 52 (52.5%) were female. Reduced ejection fraction was observed in 77.8% of patients, whilst 22.2% had a diagnosis of HF with preserved EF. The decompensation clinical classifications were: dry and warm = 7 (7.1%), wet and warm = 72 (72.7%), wet and cold = 15 (15.1%) and dry and cold = 5 (5.1%). The average left ventricular ejection fraction was 38.3% ± 15. AKI ocurred in 22 patients (22.2%). Comparison between patients who evolved with and without AKI showed higher mortality (36.4% vs 10.4%, p = 0.004) and the need for IMV (54.5% vs 13%, p = 0.0001) in the first group. There was no significant difference regarding the length of in-hospital stay (22.9 ± 19 vs 18.8 ± 16 days, p = 0.26). Conclusions: The occurrence of AKI was frequent in patients with decompensated HF requiring hospitalization, affecting approximately one out of five patients. This complication was significantly associated with increased mortality and the need for IMV during hospitalization.

Post-evaluation of ecological redevelopment is a good method for its achievements. The eco-engineering technologies and achievements of landscape water reconstructed from aquaculture ponds in Shanghai Chenshan Botanical Garden have been introduced in this study. The sediments and water quality were also sampled and tested for basic physicochemical parameters and heavy metal concentration. The ecological redevelopment of landscape water reconstructed from aquaculture ponds was evaluated using the Nemero comprehensive pollution index method. The results shown that nutrients including organic matter, organic nitrogen and their ratio of sediment were found to be in a state of moderate pollution, while their ecological risk of heavy metals was low. Although total nitrogen and total phosphorus of water quality was really higher than that of other indexes, the decline trends of ammonia nitrogen, total nitrogen and total phosphorus was obvious presented over time. In general, this is a good example that redevelopment of water ecosystems from aquaculture ponds using eco-engineering technologies.

The influence of post-processing conditions on the magnetic properties of amorphous and nanocrystalline microwires have been thoroughly analyzed, paying attention on the influence of magnetoelastic, induced and magnetocrystalline anisotropies on the hysteresis loops of Fe-, Ni- and Co-rich microwires. We showed that magnetic properties of glass-coated microwires can be tuned by the selection of appropriate chemical composition and geometry in as-prepared state or further considerably modified by appropriate post-processing, which consists of either annealing or glass-coated removal. Furthermore, stress-annealing or Joule heating can further effectively modify the magnetic properties of amorphous magnetic microwires owing to induced magnetic anisotropy. Devitrification of microwires can be useful for either magnetic softening or magnetic hardening of the microwires. Depending on the chemical composition of the metallic nucleus and on structural features (grain size, precipitating phases) nanocrystalline microwires can exhibit either soft magnetic properties or semi-hard magnetic properties. We demonstrated that the microwires with coercivities from 1 A/m to 40 kA/m can be prepared.

The article presents the author’s works in the field of modifications and modeling of the PQC CSIDH algorithm on non-cyclic supersingular Edwards curves and its predecessor CRS scheme on ordinary non-cyclic Edwards curves are reviewed. Lower estimates of the computational speed gains of the modified algorithms over the original ones are obtained. The most significant results were obtained by choosing classes of non-cyclic Edwards curves connected as quadratic twist pairs instead of cyclic complete Edwards curves, as well as the method of algorithm randomization as an alternative to “constant time CSIDH.” It is shown that in the CSIDH and CSIKE algorithms, there are two independent cryptosystems with the possibility of parallel computation, eliminating the threat of side-channel attacks. For the CRS scheme, there are four such cryptosystems. Integral lower bound estimates of the performance gain of the modified CSIDH algorithm are obtained at 1.5 ∙ 29, and for the CRS scheme are 3 ∙ 29.

Introduction: Outcome measures using telerehabilitation (TR) in the context of post-stroke rehabilitation is an area of emerging research. The current review assesses the literature related to TR for patients requiring post-stroke rehabilitation. The purpose of this study additionally is to survey the outcome measures used in TR studies and to define which parts of the International Organization of Functioning are measured in trials. Methods: TR studies were searched in Cochrane Central Register of Controlled Trials, PubMed, Embase, Scopus, Google Scholar, and Web of Science from 2016 to June 2023. Two reviewers individually assessed the full text. Disagreements about inclusion or exclusion were determined by consensus or by checking with a third reviewer. Results: A total of 24 studies were included in the current review. The results were synthesized and reported considering the implications of the results within clinical practice, areas of investigation, and strategic implementation. Conclusions: The current scoping review recognized a wide range of outcome measures used in TR studies and helped elucidate gaps in the current use of outcome measures in the literature. The scoping review also informs researchers and end users (i.e. clinicians and policymakers) regarding the most suitable outcome measures for TR.

In this study, a case of acute cattle death was investigated. The pathogen was identified, and its molecular characteristics and vector were analysed. This study provides a reference for the prevention and control of babesiosis and the healthy breeding of cattle. In this study, unengorged and engorged Rhipicephalus microplus ticks were collected from the Chongqing area. The unengorged ticks were cultured on cattle under laboratory conditions, and the engorged ticks were cultured to lay eggs. In the process, the cattle suddenly died at 12 days from the bite of an unengorged R. microplus tick. In addition, the larvae hatched from R. microplus eggs, which were cultured on the other cattle, and the experimental cattle died in approximately 14 days. Blood was collected from a second dying and stored at 4 ℃ for one week. Two millilitres of anticoagulated blood was injected subcutaneously into the third cow without piriformis infection. On the fourth day, the body temperature rose to 41 ℃ with slight lymphadenopathy. On the fifth day, the cow suddenly fell and died approximately 4 hours later. DNA was extracted from the blood of all dead cattle and amplified by PCR with piriformis universal primers. The results showed that the cattle were infected with Babesia bovis. The phylogenetic tree based on 18S rRNA showed that the Chongqing strain of B. bovis, which caused the death of cattle, was closely related to the Yunnan strain in China and had the same taxonomic status as the Spanish strain. This case report will draw people's attention to B. bovis once again, and positive control measures should be taken to reduce the losses of farmers to achieve the goal of healthy breeding.

Excessive intake of fluoride, one of the trace elements to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male Institute of Cancer Research mice without carriage of pathogenic bacteria were selected. All mice were fed adaptively for one week, and then randomly divided into 5 groups: control (K) group, model (F) group, low-dose (LT) group, medium-dose (MT) group and high-dose (HT) group. The control and model group were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT) and 160 mg/kg (HT) TMP were fed by gavage for two weeks with the maximum gavage volume of mice is 0.2ml/10g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by intraperitoneal injection on the last day of the experiment. The results of this study showed that compared with the model group, TMP alleviated the pathological changes of liver induced by fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST and MDA (P <0.05), and increased the levels of T-AOC, T-SOD and GSH (P <0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px and SOD in liver compared with model group (P <0.05). In conclusion, TMP can inhibit oxidative stress by activating Nrf2 pathway and alleviate liver injury induced by fluoride.

Experimental quantification of retention factors related to post-fire strength as well as post-fire ductility of intentionally selected stainless steel grades applied in construction is the objective of research presented here. These steel grades are characterized by a two-phase austenitic-ferritic microstructure of the duplex type. In this context two mutually corresponding chromium-nickel-molybdenum steel grades have been subjected to analysis, namely X2CrNiMoN22-5-3 steel belonging to the standard duplex group (DSS 22% Cr) and X2CrMnNiN21-5-1 steel belonging to the lean duplex group (LDSS). The similarities and differences in the mechanical properties exhibited by these steel grades after effective cooling, following more or less prolonged simulated fire action conforming to several development scenarios, have been identified and indicated. The resistance of given steel grade to permanent structural changes induced by the heating program proved to be the critical factor determining these properties and resulting in many cases in increased susceptibility to brittle fracture.

Abstract: Background and objective: Propofol is an anesthetic agent that is frequently used in anesthesia induction, maintenance and sedation. Propofol has severe side effects such as hypotension, bradycardia and respiratory depression. Although propofol is commonly used, there is no known antidote for its toxic effects. An approach to prevent toxic effects of propofol would be beneficial. The aim of this study was to assess the effects of intravenous lipid emulsion (ILE) therapy in the prevention of depressive effects of propofol on cardiovascular and respiratory systems. Materials and methods: Twenty-eight Sprague-Dawley adult rats were randomly divided into 4 groups. The saline-administered group was determined as the Control group. The second group was administered propofol (PP group); the third group was administered ILE (ILE group), and the fourth was administered propofol with ILE therapy (ILE+PP group). Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Mean arterial blood pressure (MAP), Respiratory rate (RR), Heart rate (HR) and mortality were recorded at 10 points during 60 minutes. A repeated measures linear mixed-effect model with unstructured covariance was used to compare the groups. Results: In the PP group, SBP, DBP, MAP, RR and HR levels were declining steadily; all rats in this group died after 60 minutes. In the ILE+PP group, after a while, the decreased SBP, DBP, MAP, RR and HR levels increased SBP, DBP, MAP, RR and HR levels of the Propofol group were found to be significantly lower than those of the other groups (p<0.01). The mortality rate was 100% (surviving period, 60 min) for the PP group, whereas 0% for the ILE, ILE+PP and Control groups. Conclusion: Our results suggest that undesirable side effects that can be seen after propofol application such as hypotension, bradycardia and respiratory depression might be prevented by using ILE therapy.

Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.

Abstract Congenital rubella syndrome is a constellation of birth defects that can have devastating consequences, impacting approximately 100,000 births worldwide each year. The incidence is much lower in countries that routinely vaccinate their population. In the US, postnatal immunization of susceptible women is an important epidemiological strategy for the prevention of rubella. However, concerns that co-administration of Rubella vaccine with other immunoglobins (i.e., Rhogam) could comprise vaccine efficacy has produced warnings that can delay the administration of Rubella vaccination postpartum, leaving women susceptible in a subsequent pregnancy. We aimed to address whether co-administration of Rubella vaccine and Rhogam decreased antibody responses as compared to those receiving only Rubella vaccination. This retrospective cohort study utilized clinical data from 80 subjects who received Rubella vaccine and Rhogam after delivery and 43 subjects received Rubella vaccine alone. Maternal demographics, pregnancy complications and rubella status at the start of a subsequent pregnancy were recorded for analysis. Overall, the two cohorts had similar baseline characteristics; however, lower parity was noted in the participants having both Rubella vaccination and Rhogam. Based on maternal antibody IgG index for rubella during the next pregnancy, we observed that 88% of the Rhogam + Rubella vaccine group had positive titers, which was not significantly different than the 81% in the Rubella vaccine only cohort (p=0.36). In conclusion, no differences in the rubella immunity status in a subsequent pregnancy were observed in those mothers administered both Rubella vaccine and Rhogam concurrently. Given these findings, warnings against co-administration of Rubella vaccine in combination with other immunoglobulins should be discontinued.

Sepsis is a life-threatening condition with high hospital mortality. Elevated mortality has also been observed in patients after hospital discharge due to post-sepsis syndrome (PSS). The etiology of PSS is still not entirely known, but it involves inflammation. Plasma extracellular vesicles (EVs) are recognized as a unique mechanism of intercellular communication in inflammatory processes. It has been reported that EV microRNA (miRNA) production during the acute sepsis phase may persist until after disease resolution and is associated with PSS. We employed mass spectrometry and qPCR analysis to determine the protein and miRNA composition of plasma-derived EVs of 36 patients during sepsis-related hospitalization, immediately after ICU discharge (post-sepsis), and three, six, twelve, and up to 36 months post-sepsis. We determined that patients’ immune system cells were the primary EV source. Fifteen differentially expressed EV miRNAs (DEmiRs) were identified in samples from septic patients compared to the control group. Predictive analyses revealed that these DEmiRs could influence inflammation by modulating pathways mediated by NF-κB, STAT3, and TLR4 signaling activation. Thirteen miRNAs (-15b-5p,-16-5p,-20a-5p,-25-3p,-27a-3p,-29a-3p,-30d-5p,-93-5p,-146a-5p,-148a-3p,-191-5p,-195-5p,-223-3p) were downregulated in the death group compared to the survivor group, making them candidate prognostic markers of ICU survival. One year after ICU discharge, the expression of miR-21-5p and miR-195-5p were decreased in the survivor group. The miRNAs identified in the present study represent potential biomarkers for the survival prognosis of post-sepsis patients.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year mortality (from 20% to 36%). Considering the high rate of re-hospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Plastid gene expression involves many post-transcriptional maturation steps resulting in a complex transcriptome composed of multiple isoforms. Although short read RNA-seq has considerably improved our understanding of the molecular mechanisms controlling these processes, it is unable to sequence full-length transcripts. This information is however crucial when it comes to understand the interplay between the various steps of plastid gene expression. Here, the study of the Arabidopsis leaf plastid transcriptome using Nanopore sequencing showed that many splicing and editing events were not independent but co-occurring. For a given transcript, maturation events also appeared to be chronologically ordered with splicing happening after most sites are edited.

The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by GATA1 gene mutations and progresses to ML-DS through additional mutations in cohesin genes, CTCF, RAS, or JAK/STAT pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events and aberrant expression of CRLF2, JAK2 mutations, and RAS pathway activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment's role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.

Synergistic effects between reactions, reagents and catalysts can lead to minor heats of reaction and occur as an inherent result of multi-component reactions (MCRs) and their extensions. They enable syntheses to be performed at a low energy level and the number of synthesis steps to be drastically reduced in comparison with ‘classical’ two-component reactions. The very high potential for variability, diversity and complexity of MCRs additionally generates an extremely diverse range of products, thus bringing us closer to the aim of being able to produce tailor-made and extremely low-priced materials, drugs and libraries.

Background: Evaluation of nutrition programs is essential to guarantee the effectiveness of community-based management of acute malnutrition (CMAM). Methods: The Rainbow Project Supplementary Feeding Programs (SFPs) in Zambia were evaluated between years 2015-17, following implementation of new recommendations based on previous evaluations (years 2012-14). Outcomes of the program were compared with International Standards and with those of 2012-14. Cox proportional risk regression analysis was performed to identify predictors of mortality and defaulting. Results: Data for 900 under age 5 years malnourished children (48.8% male; mean age 19.7months ±9.9) were analyzed. Rainbow 2015-17 program outcomes met International Standards, for general malnutrition or stratified moderate acute malnutrition (MAM) and severe acute malnutrition (SAM). When comparing with 2012-14 outcomes, better performance was noted: mortality rates were reduced by half (5.6% vs 3.1%, p = 0.01; for SAM: 12.4% vs 6.7%, p = 0.006), with significant improvement in average weight gain and mean length of stay (p<0.001), and increased awareness of HIV status (+30%; p < 0.001). HIV infection (5.5; 1.9–15.9), WAZ < −3 at baseline (4.6; 1.3–16.1) and kwashiorkor (3.5; 1.2–9.5) remained the major predictors of mortality. Conclusion: The effectiveness of the Rainbow SFPs for child malnutrition treatment and prevention in Zambia has significantly improved after evaluation and implementation activities, with impressive outcomes which resulted in a 50% reduction in mortality.

BACKGROUND This study investigated the association of postprandial plasma glucose (PPG) with cancer mortality using a general cohort of US adults. METHODS This cohort study included 14,860 US adults who attended the third National Health and Nutrition Examination Survey from 1988 to 1994, with mortality being followed up to December 31, 2019. The experimental exposures were levels of plasma glucose, including PPG with a fasting time of 0-3.9 h (PPG_0-3.9h) and 4-7.9 h (PPG_4-7.9h), plasma glucose with a fasting time ≥ 8 h (PG_fasting), and plasma glucose at 2 h after oral glucose tolerance test (PG_2hOGTT). Plasma glucose-associated cancer mortality risk was assessed using Cox proportional hazards models. RESULTS A 1-natural-log-unit increase in PPG_4-7.9h was associated with a higher multivariate-adjusted risk for cancer mortality [hazard ratio (HR), 3.24; 95% confidence interval (CI), 1.50-7.00]. However, PPG_0-3.9h, PG_fasting, PG_2hOGTT, hemoglobin A_1c, and insulin were not significantly associated with cancer mortality. The positive association of PPG_4-7.9h with cancer mortality remained in those without a prior diagnosis of cancer. CONCLUSIONS High PPG_4-7.9h is associated with a higher cancer mortality risk in US adults. Lowering PPG_4-7.9h may reduce cancer mortality.

Breast Angiosarcoma is a rare malignancy, accounting less than 1% of all soft tissue. It comprises primitive and secondary subtypes, such as radiogenic breast angiosarcoma (RAS). Despite the multimodal treatment, angiosarcomas represent an incurable disease for many patients and represent a cause of substantial deterioration of their quality of life. Surgery represents the cornerstone in the management, but high recurrence rates are reported. Electrochemotherapy (ECT) is practicable locoregional treatment in patients with advanced angiosarcoma, in a multimodal therapeutic strategy. ECT palliative benefit includes optimal patient compliance, good local hemostasis control, and local responses. Considering that only 22 cases are described in literature, we reported a rare case of RAS treated with ECT, after a multidisciplinary approach including Next Generation Sequencing (NGS). A literature review about the feasibility of ECT in RAS management was also performed.

Despite the relative scarcity of studies focusing on pharmacotherapy in aphasia, there is evidence in the literature indicating that remediation of language disorders via pharmaceutical agents could be a promising aphasia treatment option. Among the various agents used to treat chronic aphasic deficits, cholinergic drugs have provided interesting results. In the current review, we focused on published reports investigating the impact of acetylcholine on language and further cognitive disturbances. It has been suggested that acetylcholine plays an important role in neuroplasticity and is related to several aspects of cognition, such as memory and attention. Moreover, cholinergic input is diffused to a wide network of cortical areas, which have been associated with language sub-processes. This could be a possible explanation for the positive reported outcomes of cholinergic drugs in aphasia recovery, and specifically in distinct language processes, such as naming and comprehension, as well as overall communication competence. However, evidence with regard to functional alterations in specific brain areas after pharmacotherapy is rather limited. Finally, despite the positive results derived from the relevant studies, cholinergic pharmacotherapy treatment in post-stroke aphasia has not been widely implemented. The present review aims to provide an overview of the existing literature in cholinergic pharmacotherapy interventions in post-stroke aphasia, following an integrated approach by converging evidence from neuroanatomy, neurophysiology, and neuropsychology.

Public key encryption methods are often used to create a digital signature, and where Bob has a public key and a private key. In order to prove his identity, he will encrypt something related to the message with his private key, and which can then be checked with his public key. The main current methods of public-key encryption include RSA and ECC (Elliptic Curve Cryptography), and which involve computationally difficult operations. But these operations have not been proven to be hard in an era of quantum computers. One well-known hard problem is the solving of quadratic equations with $m$ equations with $n$ variables. This is a known NP-hard problem, even in a world of quantum computers. These can be used as post-quantum signature schemes and which involve multivariate equations. In order to understand these methods, this paper outlines a simple example of implementing the oil and vinegar method, and where we have a number of unknown oil variables and a number of known vinegar variables, and where the vinegar variables help convert the hard problem into an easy one.

Temperature is a critical factor that influences the proliferation of pathogens in hosts. The impact of temperature on pathogens is commonly explored in controlled and constant temperatures. Experiments under varying environmental temperature are becoming more frequent, however, testing every temperature scenario à la carte is unachievable. One example of this is the human pathogen Vibrio parahaemolyticus (Vp) in oysters. Here, a predictive model was developed for predicting the growth of Vp in oysters under varying ambient temperature. The model was fitted and evaluated against data from experiments studying growth and inactivation of Vp in oysters at eight constant temperatures. Once evaluated, Vp dynamics in oysters were estimated at different post-harvest varying temperature scenarios affected by water and air temperature, and different ice treatment timing. The model performed adequately under varying temperature, reflecting that (i) increasing temperature, particularly in hot summers, favors a rapid Vp growth in oysters, resulting in a very high risk of gastroenteritis in humans after consumption of a serving of raw oysters, (ii) pathogen inactivation due to day/night oscillations, and more evidently, due to ice treatments, (iii) ice treatment is much more effective limiting risk of illness when applied immediately onboard compared to dockside. The model results to be a promising tool for improving the understanding of the Vp-oyster system and support studies on public health impact of pathogenic Vp associated with raw oyster consumption. Although robust validation of the model predictions is needed, initial results and evaluation show the potential of the model to be easily modified to match similar systems where the temperature is a critical factor shaping the proliferation of pathogens in hosts.

Blackberry is a fruit that has high nutritional value, a factor that has expanded its consumption worldwide. However, due to the fragility of the fruits and the high incidence of postharvest diseases, the fruits have a short shelf life. Thus, the objective of this study was to evaluate whether the application of coatings based on microfibrillated cellulose (NC) and lemongrass essential oil (EO) nanoparticles can prolong the shelf life of blackberry fruits after harvest. EO-coated blackberry fruits at nanocellulose concentrations were analyzed as follows: 0; 0.2; 0.4; 0.6 and 0.8%, in addition to the control treatment of which neither essential oil nor nanocellulose was used, for each treatment five repetitions were used. The fruits were analyzed soon after the application of the cover and at three and six days after storage. Fruit quality was assessed by soluble solids (SS), titratable acidity (TA), pH, fresh weight loss (FWL) and colorimetric parameters such as luminosity, hue angle and fruit peel chroma. Coating on EO (1000 ppm) blackberries combined with NC at concentrations of 0.2, 0.4 and 0.6% is promising in preserving blackberry fruits and reducing the process color reversal, up to six days of storage. The 0.4% NC + 1000 ppm EO conjugated coating showed no SS changes in blackberry fruits during the six days of storage.

The rapid development of quantum computing devices promises powerful machines with capabilities that solve a wide range of problems that traditional computers cannot. Therefore, quantum computers generate new threats at unprecedented speed and scale and specifically pose an enormous threat to encryption. Lattice-based cryptography is considered to be the rival to a quantum computer attack and the future of post-quantum cryptography. So, cryptographic protocols based on lattices have a variety of benefits, like security, efficiency, lower energy consumption, and speed. In this work, we study the most well-known lattice-based cryptosystems while a systematic evaluation and comparison is presented also, and focuses on their strengths and weaknesses.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating acquisition of a rapid supply of ATP for proliferation in AML. Therefore, targeting of mesothelin presents a potentially promising approach for mitigating the progression of AML through inhibition of glycolysis and mitochondrial respiration in myeloid cells.

Considering the importance of assessing the impacts resulting from a sport career, this study aimed at developing and validating a semi-structure interview guide suitable for quantifying the socio-demographic and epidemiological profile of former professional football players. Based on the theoretical frameworks and several methodological procedures, an interview guide was de-veloped, consisting of 3 areas of conceptual organization (A1. Biographical data; A2. Career data; and A3. Post-Career Transition data) and 8 data collection categories (C1. Personal data; C2. Pro-fessional data; C3. Socio-demographic pathway in the post-career; epidemiological pathway; C4. Epidemiological pathway; C5. Moment of leaving the career; C6. Socio-demographic pathway in post-career; C7. Epidemiological pathway in the post-career; and C8. Perceptions on post-career planning). The construction and validation of the interview guide following 4 steps: Ad hoc con-struction of the interview guide (step 1); Review of the interview guide by a panel of experts (step 2); Definition of procedures and protocol for the application of the interview (step 3); Application of the pilot study for face validation of the interview guide (step 4). Thus, in procedural terms, four stages were considered for the construction and validation of the interview guide, namely the Ad hoc construction of the interview guide (i), the review of the in-terview guide by a panel of experts (ii), definition of procedures and protocol for the application of the interview (iii), and the application of the pilot study for the face validation of the interview guide (iv). The results showed that the interview guide for the study of the impacts of the sports careers on the quality of life of Portuguese former football players shows reliability for the collec-tion of qualitative and quantitative information from the respective content analysis. The use of the interview guide characterizes the path of former player, providing information and knowledge on the socio-demographic and epidemiological impact factors resulting from their post-career (sports retirement).

The pandemic was an enormous experience all over the world. The type of living, working and study were changed irreversibly. Facing the opportunity to establish old frames of education in universities is impossible. The adoption of new ways of teaching and assessments reveal their convenience and in the same way their weak points. In response to that stage, on 14 December 2022, the EU parliament accepted the "Digital Decade Policy Programme 2030", for the establishment of a digital transformation community (EU 2022). Trakia University had an online assessment system, quizzes for self-training, and final exams, developed in 2008 on Moodle virtual learning environment. During the pandemic, online exams and lectures were conducted using platforms like BigBlueButton in Moodle or Google Meets. The article gives the results of online exams before, during, and after the pandemic. The outcome, without doubt, displays the lowering knowledge level or performance during the social isolation due to COVID-19, and after, and the reasons are discussed. During the second year of the pandemic was mentioned also a high dropout of students. Now the situation is returning to the previous levels, before the pandemic, but the quality of education is not yet reached. The article values the grades results of session exams and has the intention to clarify the influence of the pandemic period on the excellence of high institution education.