Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is characterized by biphasic seizures following febrile viral infections and delayed reduced diffusion of the cerebral white matter on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) (bright tree appearance, BTA). However, hypoxic encephalopathy with biphasic seizures and AESD-mimicking imaging findings has not been reported. Herein, we report an case of hypoxic encephalopathy due to suffocation with concomitant biphasic seizures and BTA, mimicking AESD. On day 1, a 5-month-old female was found face down with breathing cessation and deteriorating consciousness level. The electroencephalography (EEG) revealed periodic epileptic discharges, suggesting possible nonconvulsive status epilepticus. Despite the improvements in consciousness level and EEG abnormalities on day 2, her consciousness level deteriorated again with generalized tonic-clonic seizures on day 3, and head MRI-DWI revealed restricted diffusion predominantly in the subcortical areas, suggesting BTA. Treatment for acute encephalopathy resolved clinical sei-zures and EEG abnormalities. The persistence of abnormal EEG, reflecting abnormal excitation and accumulation of neurotoxic substances caused by hypoxia, may have contributed to the devel-opment of AESD-like findings. As hypoxic encephalopathy causes AESD-like biphasic seizures, monitoring the consciousness level, seizure occurrence, and EEG abnormalities even after acute symptoms have temporarily improved following hypoxia is essential.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (SARS-CoV and MERS-CoV) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to the some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summaries the possible and logic answers to these questions.

Regional anesthesia in postoperative pain management have developed in recent years, especially with the advent of fascial plane blocks. This study aims to compare the ultrasound-guided bilateral erector spinae plane block (ESPB) versus bilateral transversus abdominis plane block (TAPB) on postoperative analgesia after laparoscopic or robotic urologic surgery. This was a retrospective observational study; 97 patients (ESPB-group) received bilateral ultrasound-guided ESPB with 20 mL of ropivacaine 0.375% plus 0.5 mcg/kg of dexmedetomidine in each side at the level of T7-T9, and 93 patients (TAPB-group) received bilateral ultrasound-guided TAPB with ropivacaine 0.375% or 0.25%. The primary outcome was post-operative numeric rating scale (NRS) pain score, which was significantly lower in the ESPB-group on postoperative days 0, 2, and 3 (p=0.012, p=0.016 and p=0.004). Concerning the secondary outcomes, consumption of ropivacaine was significantly lower in ESPB-group (p<0.001) and the total amount of analgesic rescue doses was significantly lower in the ESPB-group than TAPB-group in postoperative days from 2 to 4 (1 vs 3, p>0.001). Incidence of postoperative nausea and vomiting was higher in the TAPB-group and no block related complications were observed. We conclude that ESPB provide better postoperative pain control with less consumption of local anesthetic and less total rescue analgesic therapies.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease characterized by profound fatigue, post-exertional malaise (PEM), and neurocognitive dysfunction. Immune dysregulation and gastrointestinal symptoms are commonly observed in ME/CFS patients. Despite affecting approximately 0.89% of the general population, the underlying pathophysiological mechanisms remain poorly understood. This study aimed to elucidate the relationship between immunological characteristics and intestinal barrier function in ME/CFS patients. ME/CFS patients were stratified into two groups based on their immune competence. After documentation of detailed medical records, serum and plasma samples were collected for assessment of inflammatory immune mediators and biomarkers for intestinal barrier integrity by ELISA. We found reduced complement protein C4a levels in immunodeficient ME/CFS patients suggesting a sub-group specific innate immune dysregulation. ME/CFS patients without immunodeficiencies exhibit a mucosal barrier leakage, as indicated by elevated levels of Lipopolysaccharide-binding protein (LBP). Stratifying ME/CFS patients based on immune competence enabled the distinction of two subgroups with different pathophysiological patterns. The study highlights the importance of emphasizing precise patient stratification in ME/CFS, particularly in the context of defining suitable treatment strategies. Given the substantial health and socioeconomic burden associated with ME/CFS, urgent attention and research efforts are needed to define causative treatment approaches.

Abstract: Type A acute aortic dissection is a serious condition within the acute aortic syndromes that demands immediate treatment. Despite advancements in diagnostic and referral pathways, the survival rate post-surgery currently sits at almost 20%. Our objective was to pinpoint clinical indicators for mortality and morbidity, particularly raised arterial lactate as a key factor for negative outcomes. Methods: All patients referred to the three cardiovascular centres between January 2005 and December 2022 were included in the study. The inclusion criteria required the presence of a lesion involving the ascending aorta, symptoms within 7 days of surgery, and referral for primary surgical repair of TAAAD based on recommendations, with consideration for other concomitant major cardiac surgical procedures needed during TAAAD and retrograde extension of TAAAD. We conducted an analysis of both continuous and categorical variables and utilized predictive mean matching to fill in missing numeric features. For missing binary variables, we used logistic regression to impute values. We specifically targeted early postoperative mortality and employed LASSO regression to minimize potential collinearity of over-fitting variables and variables measured from the same patient. Results: 633 patients were recruited for the study, out of which 449 patients had complete preoperative arterial lactate data. The average age of the patients was 64 years, and 304 patients were male (67.6%). The crude early postoperative mortality rate was 24.5% (110 out of 449 patients). The mortality rate did not show any significant difference when comparing conservative and extensive surgeries. However, malperfusion had a significant impact on mortality [48/131 (36.6%) vs 62/318 (19.5%), p<0.001]. Preoperative arterial lactates were significantly elevated in patients with malperfusion. The optimal prognostic threshold of arterial lactate for predicting early postoperative mortality in our cohort was ≥ 2.6 mmol/L. Conclusion: The arterial lactate concentration in patients referred for TAAAD is an independent factor for both operative mortality and postoperative complications. In addition to mortality, patients with an upper arterial lactate cut-off of ≥2.6 mmol/L face significant risks of VA ECMO and the need for dialysis within the first 48 hours after surgery. To improve recognition and facilitate rapid transfer and surgical treatment protocol, more diligent efforts are required in the management of malperfusion in TAAAD.

According to the current European and Italian scenario related to urban re-generation, cultural and landscape heritage, valorisation is being also enhanced by the activation of innovative processes. These involve the development of methodologies and tools that are able to address decision-making processes among low entropy economy, complex values and creative practices. In this perspective, the research aims to investigate the possibilities of developing a Cultural Heritage Low Entropy Enhancement (CHLEE) approach by considering how the complex values of cultural heritage can vary not only through a physical transformation of spaces but also through a program of uses and activities able to produce new values, where the human experience is essential. This type of model modifies the objectives that characterise the valorisation of cultural heritage and landscape, recognising that the fruition is no longer “consumerist” but “experiential”. A crucial role is represented by the heterogeneity of creative practices that contribute to the identificationidentifying and implementation ofimplementing innovative management and governance models. The present paper explores the components of creative regenerative processes, based upon the ex-post evaluation of some Italian experiments, across the PROMETHEE-GAIA multi-criteria method, to understand how creative experiences are building innovation ecosystem thanks to low entropy economy and improve the ex-ante evaluation for new strategies and policies.

Ménière's disease (MD) has an unclear cause. The microvascular dysregulation of the inner ear has been increasingly pointed as a potential contributor. This study investigates the prevalence of cardiovascular risk factors (CVRFs) in MD patients compared to those with posterior circulation cerebral infarction (POCI). CVRFs like hypertension, diabetes, dyslipidemia, obesity, coronary heart disease, and smoking were assessed in both MD and POCI patients. Brain MRI identified POCI etiology as "small vessel occlusion" (SVO) or "other etiology" (OE). The study included 64 MD and 84 POCI patients. Compared to MD, POCI OE showed a higher prevalence of CVRFs across various age groups, including hypertension, diabetes, dyslipidemia, and smoking. Notably, the odds of having POCI OE were significantly higher for individuals with hypertension and smoking. On the other hand, POCI SVO showed similar prevalence of CVRFs compared to MD. This study reveals no significant difference in CVRF prevalence between MD and smaller vessel POCI. However, a clear distinction emerges when comparing MD to POCI with involvement of larger blood vessels. Further research is needed to confirm these findings and explore potential shared risk factors between POCI (SVO) and MD.

Extracorporeal membrane oxygenation (ECMO) is an established rescue therapy for patients with chronic respiratory failure waiting for lung transplantation (LTx). The therapy inherent immobilization may result in fatigue, consecutive deteriorated prognosis and even lost eligibility for transplantation. We conducted a feasibility study on a novel system designed for the deployment of a mobile ECMO device, enabling physical exercise of awake patients prior to LTx. The system comprises a novel mobile oxygenator with a directly connected blood pump, a double lumen cannula, gas blender and supply, as well as control, and energy management. In-vitro experiments included tests regarding performance, efficiency, and blood damage. A reduced system was tested in vivo for feasibility using a novel large animal model. Six anesthetized pigs were first positioned in supine position, followed by a 45° angle, simulating an upright position of the patients. We monitored performance and vital parameters. All in-vitro experiments showed good performance for the respective subsystems and the integrated system. The acute invivo trials of 8h duration confirmed the results. The novel mobile ECMO-system enables adequate oxygenation and decarboxylation sufficient for, e.g., physical exercise of designated LTx-recipients. These results are promising and suggest further preclinical studies on safety and efficacy to facilitate translation into clinical application.

Cardiovascular Diseases (CVDs) are still menacing and killing adults worldwide, notwithstanding the tremendous effort, to decrease their related mortality and morbidity. Lately, a growing body of evidences indicated that inflammation plays a pivotal role in the pathogenesis and complications of CVDs. A receptor of the immunoglobulin superfamily, triggering receptor expressed on myeloid cells -1 (TREM-1) was shown to induce and to amplify the inflammation in both acute and chronic diseases pathogenesis and progression and hence it is one of the important factors that complicates CVDs. Thus, studies endeavored to investigate the role played by TREM-1 in CVDs with respect to their etiologies, complications and possible therapeutics. We examined here, for the first time, the most relevant studies regarding TREM-1 involvement in CVDs. We summarized the finding after critically analyzing them and made some suggestions for furtherance of the investigations with the aim to utilize TREM-1 and its pathways for diagnostic, management and prognosis of CVDs. Overall, TREM-1 was found to be involved in the pathogenesis of acute and chronic cardiovascular conditions like Acute myocardial infraction (AMI) and atherosclerosis as well. Although most therapeutic approaches are yet to be elucidated, present research outcome displays a promising future to utilize TREM-1 pathway as potential target to understand and manage CVDs.

Traditionally, palliative care (PC) systems focused on the needs of advanced cancer patients. But, most patients needing PC have end-stage organ diseases. Similarly, PC models focused on the needs of patients in hospice or at home; however, in most cases PC is provided in acute hospitals. Indeed, the symptom burden that these patients experience in the last year of life frequently forces them to seek care in Emergency Department. The majority of them are admitted to the hospital and many die. This issue poses important concerns. Despite the efforts of attending healthcare professionals, inhospital patients do not receive optimal care near the end-of-life. Also, evidence is emerging that delay in identifying patients needing PC have a detrimental impact on their quality of life (QoL). Therefore, there is an urgent need to early and properly identify these patients among those hospitalized. Several trials reported the efficacy of PC in improving the QoL in these patients. Each hospital should ensure that a multidisciplinary PC team is available to support attending physicians to achieve the best QoL for both PC patients and their families. This review discusses the role and the impact of inhospital PC in patients with end-stage disease or advanced cancer.

Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which alter the functions of domains to either bind to methylated DNA or interact with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We tried to elucidate RTT through evolution and structure assessment of MeCP2, CDKL5, and FOXG1, by focusing on their binding partners and disordered structures. Here, we provide insight into the similarities of the FOXG1 and MECP2 binding partners evolution and function. On the other hand, we suggest that CDKL5 could be a potential candidate for a classical RTT treatment, particularly based on its disordered structure that spans after the catalytic domain to the C-terminus, which shows abundant linear motifs that can bind to molecules with divergent structures of similar affinity. Additionally, we provide insight into the relationship between disordered structure and disease.

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases, and psychiatric disorders. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants, and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses, and chronic diseases. KYN, kynurenic acid, xanthurenic acid, and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2, 3-oxygenases, and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines, and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia, and autism spectrum disorder.

Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.

Work has begun in earnest to formulate a post-2020 Global Biodiversity Framework which will outline the vision and targets for the next decade of biodiversity conservation and beyond. However, the performance of the 2011-2020 Strategic Plan for Biodiversity suggests that even a meaningful target can fail to deliver if not accompanied by fit-for-purpose indicators. Here we provide a review of how ‘protected area’ effectiveness was addressed in the 2011-2020 plan and based on this, provide recommendations for fit-for-purpose indicators that will measure how such efforts contribute to the conservation of biodiversity. Indicators need to be built on quantitative data from site-level biodiversity monitoring of species and ecosystems combined with measurements of the state of nature in near-time, informed by remote-sensed products and other technologies. Additionally, indicators need to capture whether the essential elements of good management are in place including the identification of ecological values, threats, and objectives, equitable governance, and sufficient management resources and capacity. These fit-for-purpose indicators will require multilateral collaboration to galvanize support for, and resources to develop, the necessary infrastructure to collate and store information from countries.

It is widely believed that the dramatic transformation of the spherical outflows of AGB stars into the extreme aspherical geometries seen during the planetary nebula (PN) phase is linked to binarity and driven by the associated production of fast jets and central disks/torii. The key to understanding the engines that produce these jets and the jet-shaping mechanisms lies in the study of objects in transition between the AGB and PN phases. I discuss the results of our recent studies with high-angular-resolution (with ALMA & HST) and at high-energies (with GALEX, XMM-Newton & Chandra) of several such objects, which reveal new details of close binary interactions and high-speed outflows. These include two PPNe (the Boomerang Nebula and IRAS16342-3814), and the late carbon star, V Hya. The Boomerang is notable for a massive, high-speed outflow that has cooled below the microwave background temperature, making it the coldest object in the Universe. IRAS16342 is the prime example of the class of water-fountain PPNe (very young PPNe with high-velocity H₂O masers) and shows the signature of a precessing jet. V Hya ejects high-speed bullets every 8.5 years associated with the periastron passage of a companion in an eccentric orbit. I discuss our work on AGB stars with strongly-variable high-energy (FUV, X-ray) emission, suggesting that these objects are in the early stages of binary interactions that result in the formation of accretion disks and jets.

The physiological response to a psychological stressor broadly impacts energy metabolism. In-versely, changes in energy availability affect the physiological response to the stressor in terms of hypothalamus, pituitary adrenal axis (HPA) and sympathetic nervous system activation. Glu-cocorticoids, the endpoint of the HPA axis, are critical checkpoints in endocrine control of ener-gy homeostasis and have been linked to metabolic diseases including obesity, insulin resistance and type 2 diabetes. Glucocorticoids, through the glucocorticoid receptor, activate transcription of genes associated with glucose and lipid regulatory pathways and thereby control both physi-ological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of glucocorticoid functions in energy metabolism and systemic metabolic dysfunc-tion, particularly focusing on glucose and lipid metabolism. There are elements in the external environment that induce lifelong changes in the HPA axis stress response and glucocorticoid levels, the most prominent are early-life adversity, or exposure to traumatic stress. We hypothe-sise that when the HPA axis is so disturbed after early-life adversity, it will fundamentally alter hepatic gluconeogenesis, inducing hyperglycaemia, and hence crystalise the significant lifelong risk of developing either the metabolic syndrome, or type 2 diabetes. This gives a “Jekyll and Hyde” role to gluconeogenesis, providing the necessary energy in situations of acute stress, but driving towards pathophysiological consequences when the HPA axis has been altered.

Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity , stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression using recently proposed MRI method, macromolecular proton fraction (MPF) mapping. The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, 2 severe) at 13.5±10.0 months post-recovery, with matched controls without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n=38) included participants with neurological COVID-19 complications, excluding clinical depression. Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of PCD presence and severity according to Hamilton scores. The number of post-COVID symptoms was a significant predictor of PCD presence while the number acute of symptoms was a significant predictor of PCD severity. This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Rapid post-earthquake damage diagnosis of bridges can guide decision-making for emergency response management and recovery. This can be facilitated using digital technologies to remove the barriers of manual post-event inspections. Prior mechanics-based Finite Element (FE) models can be used for post-event response simulation using the measured ground motions at nearby stations; however, the damage assessment outcomes would suffer from uncertainties in structural and soil material properties, input excitations, etc. For instrumented bridges, these uncertainties can be reduced by integrating sensory data with prior models through a model updating approach. This study presents a sequential Bayesian model updating technique, through which a linear/nonlinear FE model, including soil-structure interaction effects, and the foundation input motions are jointly identified from measured acceleration responses. The efficacy of the presented model updating technique is first examined through a numerical verification study. Then, seismic data recorded from the San Rogue Canyon Bridge in California are used for a real-world case study. Comparison between the free-field and the foundation input motions reveals valuable information regarding the soil-structure interaction effects at the bridge site. Moreover, the reasonable agreement between the recorded and estimated bridge responses shows the potentials of the presented model updating technique for real-world applications. The updated FE model is considered as the digital twin of the bridge and can be used to analyze the bridge and monitor the structural response at element, section, and fiber levels to diagnose the location and severity of any potential damage mechanism.

Endometriosis is an oestrogen-dependant reproductive disease, with genetic, vascular, neural, inflammatory and auto-immune characteristics. There are many theories about the etiology of endometriosis, however, all of these theories have limitations and do not explain all the locations that endometriosis is found or types of patients with endometriosis. The objective of this paper is to postulate the hypothesis that endometriosis is caused by Maternal Microchimerism, the presence of maternal cells in the fetus. A literature review was conducted, analysing the characteristics, current etiological theories of endometriosis, theory limitations and relationship of maternal microchimerism and endometriosis. At time of writing, there was no literature on maternal microchimerism and endometriosis. These results suggest that Maternal Microchimerism could be a cause of endometriosis. This could account for the genetic and auto-immune characteristics seen in people with endometriosis, inducing a micro-environment for vascular, neural and epigenetic changes. This could also account for account for endometriosis seen in non-menstruating patients, such as men, fetuses and post-menopausal women and endometriosis found in non-peritoneal locations. If the hypothesis of Maternal Microchimerism is correct, endometriosis could be considered a pregnancy-related disease that could affect all humans, changing the accepted demographics of patients and potentially new diagnostic techniques and treatment options for patients with endometriosis. Further studies are needed to test this hypothesis.

Role identity theory describes the purpose and meaning in life that comes, in part, from occupying social roles. While robustly linked to health and well-being, this may become, however, when an individual is unable to fulfil the perceived requirements of an especially salient role in the way that they believe they should. Amid high rates of mental illness among public safety personnel, we interviewed a purposely selected sample of 21 paramedics from a single service in Ontario, Canada to explore incongruence between an espoused and able-to-enact paramedic role identity. Situated in an interpretivist epistemology, and using successive rounds of thematic analysis, we developed a framework for role identity dissonance wherein chronic, identity-relevant disruptive events cause emotional and psychological distress. While some participants were able to recalibrate their sense of self and understanding of the role, for others, this dissonance was irreconcilable, contributing to disability and lost time from work. In addition to contributing a novel perspective on paramedic mental health and well-being, our work also offers a modest contribution to the theory in using the paramedic context as an example to consider identity disruption through chronic workplace stress.

Although there are a large number of databases available for regulatory elements, bottleneck has been created by the lack of bioinformatics tools for predicting types of mechanisms underlying actions of regulatory elements. To reduce the gap, we developed ARabidopsis Transcription regulatory Factor Domain-domain interaction Analysis Tool- Liquid-liquid phase separation (LLPS), Oligomerization, GO analysis (ART FounDATion-LOG), a useful toolkit for protein-nucleic acid interactions (PNI) and protein-protein interactions (PPI) analysis based on domain-domain interaction (DDI). LLPS, protein oligomerization, structural properties of protein domains, and protein modifications are major components in orchestrating spatio-temporal dynamics of PPI and PNI. Our goal is to integrate PPI/PNI information into development of prediction model for identifying important genetic variants in peach. The program unified inter-database relational keys by protein domains for facilitating inference from the model species. Key advantage of the program lies in the integrated information of related features: LOG, structural characterization of domain (e.g. domain linker, intrinsically disordered regions, DDI, domain-motif (peptide) interaction, beta-sheet and transmembrane helices), and post-translational modification. We provided simple tests to demonstrate how to use the program. The program may be applied to other eukaryotic organisms. The program codes and data are freely available for download at and https://sourceforge.net/projects/artfoundation-log/.

Our primary objectives were a) to determine the need for, and the availability of point-of-care testing (POCT) for infectious diseases and b) to recommend point-of-care testing strategies and spatial care paths (SCPs) that enhance public health preparedness in regional districts of Thua Thien Hue Province (TTHP), Central Vietnam, where we conducted field surveys. Medical professionals in 7 community health centers (CHCs), 7 district hospitals (DHs) and 1 provincial hospital (PH) participated. Survey questions (English and Vietnamese) determined the status of diagnostic testing capabilities for infectious diseases and other acute medical challenges in TTHP. Infectious disease testing was limited: 6 of 7 CHCs (86%) lacked infectious disease tests. One CHC (14%, 1/7) had two forms of diagnostic tests available for the detection of Malaria. All CHCs lacked adequate microbiology laboratories. District hospitals had few diagnostic tests for infectious diseases (Tuberculosis, Syphilis), blood culture (29%, 2/7), and pathogen culture (57%, 4/7) available. The PH had broader diagnostic testing capabilities but lacked preparedness for highly infectious disease threats (e.g., Ebola, MERS-CoV, SARS, Zika, and Monkeypox). All sites reported having COVID-19 rapid antigen tests; COVID-19 RT-PCR tests were limited to higher tier hospitals. We conclude that infectious disease diagnostic testing should be improved and POC tests must be supplied near patients’ homes and in primary care settings for the early detection of infected individuals and mitigation of the spread of new COVID-19 variants and other highly infectious diseases.

The rapid advancements and the merging of hybrid quantum-classical computing, artificial intelligence (AI), machine learning (ML), and deep learning (DL) pose a potentially unseen and significant threat to encryption that may impact Post-Quantum Cryptography (PQC) transition timelines. There is a direct hybrid quantum-classical computing threat on cryptography, and there is also a direct threat AI/ML on cryptography. However, the synergistic combination of these technologies presents known and unknown threats that need attention, focus action, and research. This paper reviews Grover's Adaptive Search (GAS), which combines Grover's Algorithm with adaptive techniques to optimize search further, potentially making it even more efficient for attacking encryption. This work also examines the quantum-accelerated Harrow-Hassidim-Lloyd (HHL) Algorithm, designed to solve systems of linear equations exponentially faster than classical algorithms in certain conditions. The HHL algorithm can solve some lattice-based problems, which have implications for lattice-based encryption. This technological confluence and its potential impact on cryptography and encryption necessitate a proactive and coordinated approach to developing and implementing quantum-resistant AI/ML cryptographic solutions. This paper reviews the technological confluence and its potential implications for classical cryptography and PQC transition timelines and calls for further research.

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. Elevated concentrations of lutein found in human blood and plasma, due to high dietary intake, are beneficial against eye disease and improve cardiometabolic health. Lutein plays an important protective role against the development of neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS) and Parkinson’s disease (PD). It has also been shown to be beneficial for liver, kidney and respiratory health. Lutein, acting as a very strong antioxidant, can alleviate oxidative stress and downgrade reactive oxygen species (ROS). Oxidative stress is one of the key pathogenic mechanisms in post-COVID and mRNA vaccine injury syndromes. Recent in silico studies suggest that lutein and other naturally derived antioxidants, by docking at the site where the SARS-CoV-2 spike protein (SP) binds to the angiotensin enzyme type 2 (ACE2) receptor, may neutralize the SP-ACE2 interactions. Lutein can be added to a detoxification regimen to aid in clearing Spike protein and relieving symptoms. In agreement with Hippocrates’ dictum to “Let food be thy medicine,” this review establishes dietary lutein as a valuable therapy in the treatment of post-COVID syndrome, mRNA vaccine injury syndromes, and a wide range of other chronic illnesses.

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin releasing factor (CRF)-CRF1 receptor and GABAergic signaling dysregulation occurring in alcohol dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch clamp electrophysiology to examine the effects of alcohol dependence on the CRF-modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had less CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

There is growing recognition in research and policy of a mental health crisis among Canada’s paramedics but despite this, epidemiological surveillance of the problem is in its infancy. Just weeks before the emergence of the COVID-19 pandemic, we surveyed paramedics from a single, large, urban paramedic service in Ontario, Canada to assess for symptom clusters consistent with Post-Traumatic Stress Disorder (PTSD), major depressive disorder, and generalized anxiety disorder and to identify potential risk factors for each. In total, we received 589 completed surveys (a 97% completion rate) and found that 11% screened positive for PTSD, 15% for depression, and 15% for anxiety, with 1 in 4 active-duty paramedics screening positive for any of the three as recently as February 2020. In adjusted analyses, the risk of a positive screen varied as a function of employment classification, gender, self-reported resilience, and previous experience as a member of the service’s peer support team. Our findings support the position that paramedics screen positive for mental disorders at high rates – a problem likely to have worsened since the onset of the COVID-19 pandemic. We echo the calls of researchers and policymakers for urgent action to support paramedic mental health in Canada.

Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD) patients using neuropsychological testing. The study involved 71 post-COVID patients, with matched control groups: recovered COVID-19 individuals without complications (n=18) and individuals without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, a comparison group (noPCD, n=46) included participants with neurological COVID-19 complications, excluding clinical depression. The PCD patients showed significantly less scores in the MoCA test, decreased immediate memory recall in the Word Memory Test, decreased processing speed and higher accuracy in the Trail Making Test, and near to significant worse executive control and processing speed in the Stroop task compared to controls and the noPCD patients. The number of post-COVID symptoms negatively correlated with immediate word memory recall and processing speed among all post-COVID patients. In PCD patients, negative correlations between number of post-COVID symptoms and delayed recall, between time after recovery and immediate recall, and positive correlation between the number of acute symptoms and processing speed in the incongruent condition of the Stroop task were found. No differences between groups in Sniffin’s stick olfactory test was found. Overall, our study revealed cognitive impairment in PCD patients similar to those in major depressive disorder.

Coronavirus Disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The virus enters host cells through receptor-mediated endocytosis of angiotensin-converting enzyme-2 (ACE2), leading to systemic inflammation, also known as a “cytokine storm,” and neuroinflammation. COVID-19’s upstream regulator, interferon-gamma (IFNG), is downregulated upon the infection of SARS-CoV-2, which leads to the downregulation of ACE2. The neuroinflammation signaling pathway (NISP) can lead to neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by the formation of Lewy Bodies made of α-Synuclein protein encoded by synuclein alpha (SNCA). This study presents the pathways involved in the downregulation of ACE2 following SARS-CoV-2 infection and its effect on PD progression. Through QIAGEN’s Ingenuity Pathway Analysis, the study identifies the NISP as a top-five canonical pathway/signaling pathway and SNCA as a top-five upstream regulator. Core Analysis was also conducted on the associated molecules between COVID-19 and SNCA to construct a network connectivity map. The Molecule Activity Predictor tool was used to simulate the infection of SARS-CoV-2 by downregulating IFNG, which leads to the predicted activation of SNCA, and subsequently PD, through a dataset of intermediary molecules. Downstream Effect analysis was further used to quantify the downregulation of ACE2 on SNCA activation.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hem-atopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflam-matory biomarkers, and reconstitution of various T cell populations. Of 35 patients, four devel-oped LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.

Health services research is a multidisciplinary discipline that aims to improve population health by studying healthcare services' organization, delivery, and financing. Over time, the field has worked to define its boundaries and establish a set of core research topics and methods addressing population wellbeing, access, quality, and cost. Although the influence of health technology is significant, our literature survey on health services research showed that SCs in general—containing their management, cost, and policy—had received little attention. Importantly, our assessment also showed that the system’s readiness to handle supply policy and supply device deficiencies like those encountered during pandemic was hardly ever mentioned. Reduced open areas and water bodies, deteriorating infrastructure, and changes in the biological morphology all affect cities’ uncontrollable and unplanned growth. Urban amenities, facilities, and healthcare services were unevenly distributed due to this unchecked urban population development. In light of this, this research suggests two reliable models for site selection issues for one of Hong Kong’s main hospitals. Levels of uncertainty, infeasibility tolerance, and reliability are taken into consideration. Then, two categories of uncertainty—symmetric and bound-ed—were examined. As a result, the challenge of scheduling in uncertainty has been considered, and potential solutions have been presented using a specified probability distribution function. The paper concludes by introducing the specific justice and health problems and outlining four typical strategies. In order to ensure that medications and other healthcare supplies are produced, distributed, and given to patients, a vast network of systems, components, and procedures must be effectively managed. This research contributes in this regard. Also, its grantee fairness in health systems and the populations health locally, nationally, and globally. It highlights health inequity, advances the measurement of health inequity, and promotes public dialogues on health inequity.

The Impact of Event Scale-Revised (IES-R) is the most popular measure of post-traumatic stress disorder (PTSD), which has been recently validated in Arabic. This instrumental study aimed to determine optimal cutoff scores of the IES-R and its subscales in Arab samples of psychiatric patients (N = 168, 70.8% females) and healthy adults (N = 992, 62.7% females) from Saudi Arabia during the COVID-19 pandemic as an ongoing collective traumatic event. Based on a cutoff score of 14 of the Depression Anxiety Stress Scale 8-items (DASS-8), receiver operator curve (ROC) analysis revealed two optimal points of 39.5 and 30.5 for the IES-R in the samples (area under the curve (AUC) = 0.86 &amp; 0.91, p values = 0.001, 95% CI: 0.80-0.92 &amp; 0.87 to 0.94, sensitivity = 0.85 &amp; 0.87, specificity = 0.73 &amp; 0.83, Youden index = 0.58 &amp; 0.70, respectively). Different cutoffs were detected for the six subscales of the IES-R, with numbing and avoidance expressing the lowest predictivity for distress. Meanwhile, hyperarousal followed by the irritability expressed stronger predictive capacity for distress than all subscales in both samples. In path analysis, pandemic-related irritability resulted from direct and indirect effects of key PTSD symptoms (intrusion, hyperarousal, and numbing). Irritability contributed to traumatic symptoms of sleep disturbance in both samples while the opposite was not true. The findings suggest usefulness of the IES-R at a score of 30.5 for detecting adults prone to trauma related distress, with higher scores needed for screening in psychiatric patients. Various PTSD symptoms may induce dysphoric mood, which represents a considerable burden that may induce circadian misalignment and more noxious psychiatric problems/ co-morbidities (sleep disturbance) in both healthy and diseased groups.

Recent wastewater testing suggests the poliovirus is reemerging, raising questions about the efficacy of the current inactivated polio vaccine and mass vaccination to eradicate poliomyelitis. The present study reassessed reported outcomes from the placebo-control study of the 1954 Salk inactivated poliomyelitis vaccine field trial, which studied a population of 1,829,916 U.S. school children from the first three grades. The placebo-control study of the trial reported that the polio vaccine was 80% to 90% effective in reducing cases of laboratory confirmed paralytic poliomyelitis, 60% to 70% effective against type 1 of the virus, and greater than 90% effective against types 2 and 3 of the poliovirus. However, these outcomes are reported as relative risk reductions, and the absolute risk reductions of the 1954 polio vaccine field trial were never reported to the public. The present paper’s analysis reveals to the public for the first time that the inactivated poliomyelitis vaccine's absolute risk reduction of laboratory confirmed paralytic poliomyelitis in the placebo-control study is 0.01% to 0.02%, an extraordinarily low clinical effect that impugns the Salk polio vaccine’s reported effectiveness. Furthermore, absolute risk reductions for the three poliovirus types are 0.01%, 0.00%, and 0.01%, respectively. Outcome reporting bias in the 1954 inactivated poliomyelitis vaccine field trial casts doubt on eradication of the poliovirus through mass vaccination.

The official recommendations to manage COVID-19 in the outpatient setting focus on high-cost drugs (remdesivir, nirmatrelvir-ritonavir, molnupiravir), suffering from many problems. Therefore, one may consider also other treatments meeting these criteria: • promising effectiveness, based on favorable randomized controlled trials (RCTs) of sufficient validity. Even without definitive evidence, physicians and informed patients can consider them if they are also: • safe, to the state of knowledge • with a very favorable opportunity cost • biologically plausible/not implausible • accessible • without major commercial sponsors in the trials promoting them, and with researchers without major conflicts of interests. The main focus is on a limited group of functional foods and some their active ingredients, with further mention of other substances of different origin, yet fully meeting all the aforementioned criteria. The functional foods and substances described and discussed certainly do not cover all the known effective therapies for COVID-19 (in one case also for Long-COVID), but the only therapies proposed in this paper currently satisfy all the above criteria. The supporting scientific evidence will favor meta-analyses of RCTs that include the most definitive outcome: all-cause mortality, i.e. the outcome that most fully informed people tend to prioritize. Furthermore, the reported evidence favors clinical studies of the most valid design, i.e. RCTs.

A parallel between defense powers of sovereign nations and effective immunity that guards health is relevant to demonstrate vulnerability of immune system under external forces (vaccines, drugs). History demonstrated that sovereignty (power within) of small nations often threatened or destroyed by military might of powerful nations (power without) who use false-flags and propaganda for motives that are financial-control-driven. Similarly, we propose that body’s complex immune neuroplasticity (power within, adaptive, horizontal) is stretched-thin and weakened by the external forces, particularly by vaccination of the unborn/newborn or immune-compromised individuals. Validity of genomics (innate, perpendicular) as origins of ‘hereditary’ diseases (eg, allergies, diabetes, cancers) that for a century dominated research and treatment is also challenged. In conclusion, we propose that the pressure/power from within creates life with potential to sustain health, while the pressure/power from without, weaken and destroy life.

Here, applying the theory of the generalization of the Boltzmann constant in curved space-time, we will model the mechanism by which elementary particles are formed. We will determine the relationship between gravity and each of the elementary particles that form the standard model following analogies to that of stellar bodies. In order to achieve our goal, we will propose new models for photons, quarks and gluons; with this, we will demonstrate why there are stable and unstable elementary particles; why the first family of elementary particles forms hadrons and why the second and third families cannot form hadrons; why the fermions comply with the Pauli exclusion principle and why the bosons do not comply with the Pauli exclusion principle, etc. Finally, we will analyse the generalization of the ADS/CFT correspondence and propose a theory of everything (T.O.E.).

Here we will electrically-quantum model the neutron and proton as a three-phase alternating current electric generator, for this, we will use the theory of three-phase electric generators and vector or phasor diagrams. We will use this model to hypothesize how the quarks that form neutrons and protons with a combined mass of 10 MeV/c², can generate, through quarks-antiquarks-gluon interactions, a mass of 939.56 MeV/c² for the neutron and a mass of 938.27 MeV/c² for the proton. Using quantum mechanics and the theory of the generalization of the Boltzmann constant in curved space-time we will calculate the number of quarks-antiquarks-gluons and gravitons inside a neutron. We will also analyse βˉ decay using vector diagrams, we will calculate the tension of the string T₀ and the length of the string ℓs between quarks-antiquark and finally, we will model a black hole using a neutron equivalent model. In version 2 of this article, we will update the vector diagrams of the βˉ decay and theoretically calculate the energy of the W⁻ boson, the Z⁰ boson, and the Θ angle, Θ = arc cos (W⁻/Z⁰). We will demonstrate, through vector diagrams, that quarks-antiquarks-gluon interactions are the cause of the origin of the W⁻ boson and the Z⁰ boson. We will also demonstrate how the fine structure constant α originates. It is important to make clear, in future updates, we will describe the relationship that exists between the theory described in this paper and the Isospin theory, flavour and colour theory

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were col-lected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial respondseproteins. 16S rRNA sequencing assessed mi-crobiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial inva-sion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

The study comprehensively evaluated the prognostic roles of PLR, NLR, MLR, BLR, and ELR in patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD). 619 patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics containing laboratory findings of the AECOPD patients and the blood cell counts (CBCs) of the healthy volunteers were collected. Compared with the healthy volunteers, PLR, NLR, and MLR were elevated in COPD patients in stable condition, and were further ele-vated during exacerbation. ELR showed the opposite trend. PLR, NLR, and MLR were all posi-tively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more serious airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while Elevated ELR was associated with decreased in-hospital mortality in AECOPD. A nomogram was construct to predict in-hospital mortality in AECOPD. The nomo-gram had a C-index of 0.850 (95% CI: 0.799 – 0.901) with good predictive value and clinical ap-plicability. In summary, PLR, NLR, MLR, and ELR served as predictors for clinical outcomes in patients with AECOPD.