Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

The emergence of SARS-CoV-2 mutations pose significant challenges to diagnostic tests as these mutations can reduce the sensitivity of commonly used RT-PCR assays. Therefore, there is a need to design diagnostic assays with multiple targets to enhance sensitivity. In this study, we identified a novel diagnostic target, nsp10 gene, using nanopore sequencing. Firstly, we determined the analytical sensitivity and specificity of our COVID-19-nsp10 assay. The COVID-19-nsp10 assay had the limit of detection of 74 copies/mL (95% confidence interval: 48-299 copies/mL) and did not show cross-reactivity with other respiratory viruses. Next, we determined the diagnostic performance of the COVID-19-nsp10 assay using 261 respiratory specimens, including 147 SARS-CoV-2-positive specimens belonging to ancestral strain and Alpha, Beta, Gamma, Delta, Mu, Eta, Kappa, Theta and Omicron lineages. Using the LightMix E-gene RT-PCR assay as the reference method, the diagnostic sensitivity and specificity of the COVID-19-nsp10 assay were 100%. The median Cp values for the LightMix E-gene RT-PCR and our COVID-19-nsp10 RT-PCR were 22.48 (range: 12.95-36.60) and 25.94 (range 16.37-36.87), respectively. The Cp values of the COVID-19-nsp10 RT-PCR assay correlated well with those of the LightMix E-gene RT-PCR assay (Spearman’s ρ = 0.968; P<0.0001). In conclusion, nsp10 is a suitable target for SARS-CoV-2 RT-PCR assay.

Post-ovulatory aging (POA) is an inevitable factor during some assisted reproduction technology procedures, and results in poor fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and in vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte(A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte(A_vitro) were intersected to explore the co-effects of POA. It was found that "organelles", especially "mitochondria", were significantly enriched GO terms. The expression of genes related to the “electron transport chain” and “cell redox homeostasis” pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. WGCNA analysis to explore gene expression modules specific to A_vivo. Trait-modules association analysis showed that the red modules were most associated with in vivo aging. There are a total of 959 genes in the red module, which are mainly enriched in “RNA binding”, “mRNA metabolic process”, etc. GO terms, and “spliceosome” and “nucleotide excision repair” pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. And these genes were all expressed higher in A_vivo. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study helps us understand the detailed mechanism of POA and provides strategies for researching oocyte aging.

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.

P. palmata is a viable source of nutrients with bioactive properties. The present study determined the potential role of post-extraction ultrasonication on some compositional features and antioxidant properties of resulting extracts after sequential enzymatic/alkaline treatment. No significant difference was detected in terms of protein content and recovery as well as amino acid composition of the extracts. The nitrogen-to-protein conversion factor of 5 was found to be too high for the seaweed and its enzymatic/alkaline extracts. The extracts sonicated by bath for 10 minutes and not sonicated showed the highest and lowest total phenolic contents (p<0.05), respectively. The highest radical scavenging and lowest metal chelating activities were observed for the non-sonicated sample, as evidenced by IC50 values. The extract sonicated by bath for 10 minutes showed the most favorable in vitro antioxidant properties since its radical scavenging was not significantly different from that of not sonicated sample (p>0.05), whereas its metal chelating activity was significantly higher (p<0.05). To conclude, post-extraction ultrasonication by an ultrasonic bath for 10 minutes is recommended to increase phenolic content and improve antioxidant properties of enzymatic-alkaline extracts from P. palmata.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Background: Vaccinating children against COVID-19 is an essential public health approach for preventing infection in children and adults. This study aimed to explore parents' attitudes toward and the rate of COVID-19 vaccine hesitancy among children in Oman. Methods: This cross-sectional study used an online, self-administered questionnaire. The 9-item questionnaire was validated earlier and administered between June 2021 and May 2022. Multiple logistic regression was used to determine the factors associated with vaccine hesitancy. The parents received a pre-validated Google questionnaire. Responses from the parents of children younger than 11 years of age were accepted. Results: 384 participants completed the questionnaire, including 207 males (54%). The response rate was 86% (384/447). Of the 384 participants, 69% of the parents hesitated to vaccinate their children aged 1-11-year-old children). In parents of children aged 1–4 years, parental vaccination status was significantly associated with vaccine hesitancy (odds ratio [OR]: 0.116, 95% confidence interval [CI]: 0.044–0.306; p < 0.001). Additionally, vaccine hesitancy was significantly more common in mothers than in fathers (OR: 0.451, 95% CI: 0.240–0.848; p = 0.013). . Mothers of children were 77% more likely to be hesitant than fathers (.78, 95% confidence intervals (CI) = 0.50–0.1.23; p = 0.283). Conclusion: Many parents hesitated to vaccinate their children against COVID-19. Consequently, future awareness campaigns and strategies should target new vaccines. The results of our study show that the Arabic version of the 5-point Likert Scale for Vaccination Hesitancy is a valid and reliable tool.

Many metabolic processes at the molecular level support both viral attack strategies and human defenses during Covid-19. This knowledge is of vital importance in the design of antiviral drugs. In this study, we extracted 18 articles (2021-2023) from PubMed reporting the discovery of hub-nodes specific for the liver during covid-19, identifying 142 hub-nodes. They are highly connected proteins from which to get deep functional information on viral strategies when used as functional seeds. Therefore, we evaluated the functional and structural significance of each of them to endorse their reliable use as seeds. After filtering, the remaining 111 hubs were used to get by STRING an enriched interactome of 1111 nodes (13,494 interactions). It shows the viral strategy in the liver is to attack the entire cytoplasmic translational system, including ribosomes, to take control of protein bio-synthesis. We used the SARS2-Human-Proteome Interaction Database (33,791 interactions), de-signed by us with BioGRID data to implement a reverse-engineering process that identified human proteins actively interacting with viral proteins. The results show 57% of human liver proteins di-rectly involved in Covid, a strong impairment of the ribosome and spliceosome, an antiviral defense mechanism against cellular stress of the p53 system, and, surprisingly, a viral capacity for multiple protein attacks against single human proteins that reveal underlying evolutionary-topological molecular mechanisms. Viral behavior over time suggests different molecular strategies for different organs.

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.

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this disease may have long-term adverse neurological consequences. COVID-19 occurs from the infection by a positive-sense single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The membrane fusion protein of SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme 2 (ACE2), to initiate membrane fusion between the virus and host cell. The spike protein of SARS-CoV-2 contains the furin protease recognition site and its cleavage enhances the infectivity of this virus. The binding of SARS-CoV-2 to the ACE2 receptor has been shown to downregulate ACE2, thereby increasing the levels of pathogenic angiotensin II (Ang II). The furin protease cleaves between the S1 subunit of the spike protein with the binding domain toward ACE2 and the S2 subunit with the transmembrane domain that anchors to the viral membrane, and this activity releases the S1 subunit into the blood circulation. The released S1 subunit of the spike protein also binds to and downregulates ACE2, in turn, increasing the level of Ang II. Considering that a viral particle contains many spike protein molecules, furin-dependent cleavage would release many free S1 protein molecules each of which can downregulate ACE2, while the infection with a viral particle only affects one ACE2 molecule. Therefore, the furin-dependent release of S1 protein would dramatically amplify the ability to downregulate ACE2 and produce Ang II. We hypothesize that this amplification mechanism that the virus possesses, but not the infection per se, is the major driving force behind COVID-19 associated neurological disorders.

N-methyl-D-aspartate receptors (NMDARs) are the main class of ionotropic receptor for the ex-citatory neurotransmitter glutamate. It plays a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of sev-eral subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) and/or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, excitotoxicity. The present review will discuss the physiopathological impacts of NMDAR and particularly GluN2A and GluN2B subu-nits in cognitive processes and neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease). The pharmacology of different NMDAR antagonists and their po-tentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising developments as a tomography radiotracer for NMDARs, an anxiolytic in post-traumatic stress disorder and a neuroprotective agent in Alzheimer's disease.

Whether and how P2X7 receptor knockout (KO) modulates central post-stroke pain (CPSP) induced by lesions of the ventrobasal complex (VBC) of the thalamus regarding behavioral, molecular, and electrical recording parameters remains unclear. Following the experimental protocols of a rat hemorrhage CPSP model, the VBC of the thalamus of wild-type and P2X7 receptor KO mice was injected with 10 mU/0.2 μl type IV collagenase to produce an animal model of stroke-like thalamic hemorrhage. Behavioral data showed that the CPSP group induced thermal and mechanical pain, while the P2X7 receptor KO group showed reduced thermal and mechanical pain behaviors. Molecular assessments revealed that the CPSP group had lower expression of NeuN and KCC2 and higher expression of GFAP, IBA1, and BDNF. The P2X7 KO group showed lower expression of GFAP, IBA1, and BDNF and higher expression of KCC2 than the CPSP group. The expression of NKCC1, GABAa receptor, and TrkB did not differ significantly between the control, CPSP, and P2X7 receptor KO groups. Muscimol application increased multiunit numbers and [Cl-] influx in the membrane in the CPSP group, while P2X7 receptor KO reduced multiunit activity and [Cl-] outflux. P2X4 receptor expression was significantly decreased in the 100 kb but not the 50 kb site in the P2X7 receptor KO group. Altogether, the P2X7 hypothesis of CPSP was proposed, wherein P2X7 receptor KO changed the CPSP pain behavior, numbers of astrocytes and microglia, CSD amplitude of the anterior cingulate cortex and the medial dorsal thalamus, BDNF and KCC2 expression, [Cl-], and P2X4 activation in 100 kb with P2X7 receptors. The present findings have implications for the clinical treatment of CPSP symptoms.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

The SARS-CoV-2 Omicron variant and its sublineages continue to cause COVID-19—associated pediatric hospitalizations, severe disease, and death globally. BNT162b2 and CoronaVac are among the top most widely used COVID-19 vaccines. Much less is known on the Wuhan-Hu-1 strain based vaccines in the pediatric population compared to adults. Given the worldwide need for booster vaccinations to stimulate the immune response against new Omicron variants of SARS-CoV-2, we characterized the humoral and cellular immune response against Omicron variant BA.1 in a pediatric population aged 10 to 16 years who received heterologous vaccination based on two doses CoronaVac, two doses CoronaVac (2x) plus one booster doses BNT162b2 [CoronaVac(2x) + BNT162b2 (1x)], two doses CoronaVac plus two booster doses BNT162b2 [CoronaVac(2x) + BNT162b2 (2x)], and three doses BNT162b2. We observed that [CoronaVac(2x) + BNT162b2 (2x)] vaccination showed higher anti-S1 and neutralizing antibody titers and CD4 and CD8 T cell immunity specific to the Omicron variant compared to immunization with two doses CoronaVac alone. Furthermore, from all groups tested, immunity against Omicron was highest in individuals who received three doses BNT162b2. We conclude that booster vaccination with BNT162b2 promotes greater immunity against SARS-CoV-2 in the pediatric population compared to two doses CoronaVac alone.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

Wastewater-Based Epidemiology (WBE) is currently used to monitor not only the spread of the pandemic virus SARS-CoV-2 but also for other viruses in endemic conditions, particularly in the absence of syndromic surveillance. Continuous monitoring of sewage requires high costs and significant time investment, highlighting the need for standardized methods and structured monitoring strategies. In this context, we conducted weekly wastewater monitoring in northwestern Italy, targeting Human Adenovirus (HAdV), Norovirus Genogroup II (NoVggII), Enterovirus (EV), and SARS-CoV-2. Samples collected at the entrance of treatment plants were concentrated using PEG/NaCl precipitation and viral nucleic acids were extracted and detected by real-time (RT-)qPCR. NoVggII resulted the most identified target (84.4%), followed by HAdV, SARS-CoV-2, and EV. Only HAdV and EV exhibited seasonal peaks in spring and summer. SARS-CoV-2 results compared with data previously collected in the same study area (February 2021 to September 2021) revealed a shift from an epidemic to a pandemic status, likely due to the evolution of variants. In conclusion, WBE, using standardized methods and an efficient monitoring strategy, proves valuable for virus surveillance in pandemic and epidemic scenarios, enabling the identification of temporal-local distribution patterns that are useful for making informed public health decision.

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.

Abstract: Background: Patients with diabetes are particularly susceptible to COVID-19 infection, which can result in severe respiratory illness. Methods: This study conducted a comparative as-sessment of the impact of antiviral therapy using molnupiravir and favipiravir in COVID-19 pa-tients with underlying diabetes. A cohort of one hundred individuals infected with SARS-CoV-2, diagnosed with diabetes, and consecutively admitted, was included in the present study. These patients were treated with antivirals according to local guidelines: Group F (51 cases) was treated with favipiravir – 10 days and Group M (49 cases) was treated with molnupiravir – 5 days. Re-sults: In Group F, the average hospitalization was higher than in Group M (11.29±2.27 vs. 7.14±3.16, p

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently SARS-CoV-2, al-ready four other coronaviruses have been circulating in the human population. The alpha coronaviruses NL63 and 229E and the beta coronaviruses OC34 and HKU1. These circulating coronaviruses all cause mild respiratory illness during the winter seasons and most people are already infected in early life. Could antibodies and/or T cells, es-pecially against the beta coronaviruses have offered some form of protection against SARS-CoV-2? Related is the question whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory, generated during the SARS-CoV-2 pandemic, ei-ther by infection or vaccination offer protection against future coronaviruses? Or rather than protection, could antibody dependent enhancement have taken place, a mecha-nism by which circulating corona antibodies enhance the severity of COVID-19? An-other related phenomenon, the original antigen sin, would also predict that the effec-tivity of the immune response to future coronaviruses would be impaired because of reactivation of memory against irrelevant epitopes. Current available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.

This is a SARS-CoV-2 seroepidemiological study in pediatric population(0-16 years) during BA.5 Omicron predominance period in Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies(Abs-N), representing natural infection during three sub-periods of BA.5 predominance: 01/05/2022-31/08/2022(period A), 01/09/2022-31/12/2022(period B) and July 2023(period C) and epidemiological data were collected. Additionally in period C Abs-N seronegative samples were tested for SARS-CoV-2 spike antibodies(Abs-S). A total of 878 children were tested (males:51.3%) with median age(IQR): 108(36-156) months and seropositivity during the 3 subperiods was: A:292/417(70%), B:288/356(80.9%), C:89/105(84.8%), P-value<0.001. SARS-CoV-2 seropositivity increased for from period A to C for 0-1-year (P-value: 0.044), 1-4 years (P-value: 0.028) and 6-12 years children (P-value: 0.003). Children 6-12y had the highest seroposi-tivity rates in all subperiods (A: 77.3%, B: 91.4% and C: 95.8%). A significant correlation of monthly SARS-CoV-2 median antibody titers with monthly seropositivity rates was detected (rs:0.812, P-value:0.008). During period C, an additional 12/105 (11.4%) Abs-S seropositive and Abs-N ser-onegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The increased SARS-CoV-2 seropositivity detected in current seroepidemiology study illustrates a high exposure rate during BA.5 predominance period. These data could guide public health decisions regarding immunization strategies and protection measures.

This study aimed to investigate the effect of adding Mirror Visual Feedback Therapy (MFT) after Dry Needling (DDN) on sensitivity and motor performance in patients diagnosed with Post-Needling pain from Myofascial Trigger Points (MTrPs) in lateral elbow pain patients. A randomized, controlled, two-arm pilot trial following Consolidated Standards of Reporting Trials (CONSORT) was conducted at the European University of Madrid between February 1, 2023, and June 2, 2023. A total of 49 patients (F=23, M=26) were randomly assigned to the Experimental Group Deep Dry Needling, Ischemic Compression, Cold Spray, Stretching, and Mirror Therapy (n=25), and the others receiving the same interventions without Mirror Therapy (n=24). Pre- and post-treatment assessments encompassed Post-needling pain (VAS), pressure pain threshold (PPT), two-point discrimination threshold (TPDT), and maximum hand grip strength (MHGS). Post-needling pain intensity in the EG showed statistically significant reductions (MD = 0.400, SEM = 0.271, W = 137.00, p = 0.047) following the addition of MT to the DDN protocol. Similarly, PPT exhibited significant improvements (MD = 0.148 Kg/cm2, SEM = 0.271, W = 262.00, p < 0.001). However, TPDT and MHGS did not show significant differences between initial and post-treatment measurements. The addition of MFT to DDN for MTrPS in lateral elbow pain reduced Post-needling pain and influenced on sensory perception in lateral elbow pain patients with Myofascial Trigger Points. Despite observed clinical effects not reaching statistical significance, these findings offer valuable insights for future research considerations.

Conventional MRI sequences are standard methods to monitor patients with brain tumors but have significant limitations especially after irradiation. Currently, the role of FET-PET in radiotherapy of glioblastoma is emerging, starting from target definition, response assessment and in distinguishing progression from post-irradiation changes. Recently a PET RANO criteria have been published providing optimal strategy for treatment evaluation with amino-acid PET. Earlier, a PET/RANO group reported contribution of PET imaging to radiotherapy planning and monitoring in glioma patients. Also, increasing evidence have showed advantages of amino-acid PET vs. RANO MRI for prediction of overall survival. In this narrative review we aimed to summarize published data on FET-PET based treatment response assessment to radiotherapy and focused on details in protocols.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyper inflammation, vasculitis and multi-organ failures. SARS-CoV-2 causes deterioration of numerous systems with increasing evidence implying that COVID-19 affects endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietins/Tie balance affects vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically the Angiopoietin/Tie pathway.

Cardiotoxicity is an unwanted side-effect arising from different medications. The term describes a diminution of heart function, affecting especially left ventricular ejection fraction, which can progress to heart failure. Pediatric oncology patients treated with drugs of the anthracycline group, e.g., doxorubicin, can evolve to heart failure patients in adult age. Nuclear Medicine imaging of fatty acid oxidation and glycolysis accurately describes normal and altered heart metabolism. The most common finding is a state of cardiac glycolysis, which is reflected by increased uptake of 18F-desoxyglucose (18F-FDG) at a time when fatty acid oxidation is decreased. Glycolysis has recently been recognized as being the result of coenzyme Q10 deficiency as part of adaptation to hypoxia. Low LEVF correlates with impaired fatty acid oxidation. This deficiency can arise from chemotherapy and radiation and can be corrected by supplementation. Drugs like enalapril can improve fatty acid utilization. We will review relevant Nuclear Medicine imaging studies as well as fundamental biochemical data that demonstrate this pathogenetic path.

Before December 2020, Antarctica had remained free of Covid-19 cases. The main concern during the pandemic was the limited health facilities available at Antarctic stations to deal with the disease, as well as the potential impact of SARS-CoV-2 on Antarctic wildlife through reverse zoonosis. In December 2020, 60 cases emerged in Chilean Antarctic stations, disrupting the summer campaign with ongoing isolation needs. The SARS-CoV-2 RNA was detected in the wastewater of several scientific stations. In Antarctica, treated wastewater is discharged directly into the seawater. No studies currently address recovery of infectious virus particles from treated wastewater, but their presence raises the risk of infecting wildlife and initiating new replication cycles. This study highlights the initial virus detection in wastewater from Antarctic stations, identifying viral RNA via RT-qPCR targeting various genomic regions. The virus's RNA was found in effluent from two wastewater plants at Maxwell Bay and O’Higgins Station on King George Island and the Antarctic Peninsula, respectively. This study explores the potential for reverse zoonotic transmission of SARS-CoV-2 from humans to Antarctic wildlife due to the direct release of viral particles into seawater. The implications of such transmission underscore the need for continued vigilance and research.

To better understand how immunity develops against SARS-CoV-2 during the pandemic period of 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined 8 months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after 6 months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred even among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN- or CD107a were detected early. In saliva, SARS-CoV-2-specific IgG but not IgA was detected. Interestingly, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Thus, SARS-CoV-2 infection triggers typical immune responses in humans against acute viral infections, but mucosal immune responses, which are temporarily induced early during infection, may be more important for protection than current intramuscular vaccines.

Abstract: The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on a global scale. Even though the pandemic has concluded, there remains apprehension regarding the emergence of highly transmissible variants capable of evading immunity induced by either vaccination or prior infection. The success of viral penetration is the specific amino acid residues of the Receptor Binding Motif (RBM) involved in viral attachment. This region interacts with the cellular receptor ACE2, triggering a neutralizing antibody (nAb) response. In this study, we have evaluated the immunogenicity of serum from individuals who received either a single dose or a combination of different vaccines against the original SARS-CoV-2 strain and mutated linear RBM. Despite a modest antibody response to the wild-type SARS-CoV-2 RBM, the Omicron variants exhibit four mutations in the RBM (S477N, T478K, E484A, F486V) that result in even lower antibody titers. The primary immune responses observed were directed towards IgA and IgG. While nAbs typically target the RBD, our investigation has unveiled a reduced seroreactivity within the RBD's crucial subregion, the RBM. This deficiency may have implications for the generation of protective nAbs. Evaluation of S1WT and S2WT RBM peptides binding to nAbs using microscale thermophoresis revealed a higher affinity (35 nM) for the S2WT sequence (GSTPCNGVEGFNCYF), which includes the FNCY patch. Our findings suggest that the linear RBM of SARS-CoV-2 is not an immunodominant region in vaccinated individuals. Comprehending the intricate dynamics of the humoral response, its interplay with viral evolution, and host genetics is crucial for formulating effective vaccination strategies, not only targeting SARS-CoV-2 but also anticipating potential future coronaviruses.

Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations, characterized by distinct interactomes – namely protein assemblies - under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly and disease.

Blocking the interaction of the SARS-CoV-2 spike protein with the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim in this study was to explore the efficacy of TCM treatments for SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. The antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis was found to be effective against SARS-CoV-2 infection through affecting the interaction of viral spike protein with the hACE2 protein. The active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside, respectively, found in S. baicalensis, exhibited strong inhibitory activities, targeting the viral spike protein or hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors of the interaction of the Omicron spike protein and hACE2 receptor from S. baicalensis. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

Type II pneumocytes are the target of SARS-CoV-2 which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. Here we evaluated whether the treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2–), lipid peroxidation (LPO), and thiols groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), -S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There was a significant increase in LPO and carbonyls (p≤0.03) and a decrease in TAC, NO2–, thiols, GSH, (p&lt;0.001) in COVID-19 patients. The activities of the ecSOD, TrxR, GPx, GST, GR and peroxidases were decreased (p≤ 0.04). The treatment with MT favored the activity of the antioxidant enzymes which contributed to increase TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis functioning as a glycolytic agent and inhibited the Warburg effect. Thus, MT restores the redox homeostasis which is altered in COVID-19 patients and can be used as adjuvant therapy in the SARS-CoV-2 infection.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

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.

Coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2) infection, has caused millions of infections and fatalities worldwide. Extensive SARS-CoV-2 research has been conducted to develop therapeutic drugs and prophylactic vaccines, and even though some drugs have been approved to treat SARS-CoV-2 infection, treatment efficacy remains limited. Therefore, preventive vaccination has been implemented on a global scale and represents the primary approach to combat the COVID-19 pandemic. Approved vaccines vary in composition, although vaccine design has been based on either the key viral structural (spike) protein or viral components carrying this protein. Therefore, mutations of the virus, particularly mutations in the S protein, severely compromise effectiveness of current vaccines and the ability to control COVID-19 infection. This review begins by describing the SARS-CoV-2 viral composition, mechanism of infection, role of angiotensin-converting enzyme 2, host defense responses against infection and the most common vaccine designs. Next, this review summarizes the common mutations of SARS-CoV-2 and how these mutations change viral properties, confer immune escape and influence vaccine efficacy. Finally, this review discusses global strategies that have been employed to mitigate the decreases in vaccine efficacy encountered against new variants.

To discover potential micro(mi)RNAs biomarkers of SARS-CoV-2 infection and disease progression, large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for SARS-CoV-2 infection (median 13.50 [IQR 9–24] days since symptoms initiation) and 21 healthy noninfected individuals. A totally of 1218 different miRNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2 infected patients showed significantly (fold change [FC] >1.2 and adjusted p [padj] <0.05) altered expression of 190 miRNAs. The top 10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 × 10-32 to 2.21 × 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found when patients on high- and low-flow oxygen therapy were compared. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Specific miRNA profiles are associated with COVID-19 prognosis in patients requiring oxygen flow.

Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adenoassociated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investi-gate the molecular aspects of HDV and associated liver damage. Here, we generated HDV ge-nomes modified by site directed mutagenesis aimed to: i) prevent some post-translational modi-fications of HDV antigens (HDAgs) such as Large-HDAg (L-HDAg) isoprenylation or Short-HDAg (S-HDAg) phosphorylation ii) alter the localization of HDAgs within the subcellular compartments and iii) inhibit the right conformation of the delta ribozyme. First, the different HDV mutants were tested in vitro using plasmid-transfected Huh-7 cells and then in vivo in C57BL/6 mice using AAV vectors. We found that Ser 177 phosphorylation and the ribozymal ac-tivity are essential for HDV replication and HDAg expression. Mutation of the isoprenylation domain prevent the formation of infectious particles and increase cellular toxicity and liver dam-age. Finally, altering the intracellular localization od HDAg have a profound on viral replication in vivo but liver toxicity is maintained. Mutation in the nuclear export signal impair the for-mation of infectious viral particles. These findings contribute valuable insights into the intricate mechanisms of HDV biology and have implications for therapeutic considerations

SARS-CoV-2 virulence is known to increase with lowering of environmental temperature and solar ultraviolet radiation; therefore, we have focused our real-world nationwide study concerning with COVID-19 trends and dynamics on the coldest seasons of the year in Italy, the Western country hardest hit at the onset of the pandemic, comparing the autumn-winter of 2020 (before mass vaccination but when the emergency machinery was fully operative in terms of tracing and swabs) with the autumn-winter of 2021 (after mass vaccination), and analyzing the mortality burden by age groups and life stages in the years 2019 (pre-COVID-19), 2020 (before mass vaccination) and 2021 (after mass vaccination). Methods: During the state of national health emergency, the Civil Defense Department released the aggregate data coming from the Higher Institute of Health, the Ministry of Health, the Italian Regions, and the Independent Provinces, to inform the population (58.85 million people) about the pandemic situation, daily. Among these data there were the number of contagions, performed swabs, hospitalizations in Intensive Care Units (ICU), non-ICU patients, and deaths. By means of a team effort, we have collected and elaborated all these data, comparing the COVID-19 pandemic in Italy during the autumn-winter of 2020 with the autumn-winter of 2021. Moreover, we have extracted from the database of the National Institute of Statistics the total number of annual deaths in Italy during the years 2019, 2020 and 2021, comparing them to each other in order to evaluate the mortality burden attributable to COVID-19. Results: From the autumn-winter of 2020 to the autumn-winter of 2021, the contagions increased by ≈285%, however against a ≈290% increase in the performed swabs; therefore, the mean positivity rate passed from 8.74% before mass vaccination to 8.59% after mass vaccination. The unprecedent vaccination campaign allowed a ≈251% abatement in COVID-19 deaths, and a reduction of ≈224% and ≈228% in daily ICU and non-ICU hospitalizations due to COVID-19, respectively. Regarding COVID-19 deaths, in 2020 there was a mortality excess of ≈14.3% quantifiable in 105,900 more deaths compared to 2019, the pre-COVID-19 year; 103,183 out of 105,900 deaths occurred in older adults (≥60 years), which is equivalent to ≈97.4%, while in adults over 50, the segment of population just below older adults, in 2020 there were 2807 more deaths than in 2019. Surprisingly, from the analysis of our data, it is emerged that under the age of 40 in the years 2019, 2020 and 2021 there were 7103, 6808 and 7165 deaths, respectively. This means that in subjects under 40 during 2020 there were 295 fewer deaths than in 2019, while during 2021 there were 357 more deaths than in 2020, equivalent to ≈5.2% more. Conclusions: COVID-19 is a potential life-threatening disease mainly in older adults, as they are the most vulnerable due to inherent immunosenescence and inflammaging. Extensive vaccination in this segment of population with up-to-date vaccines is the means to reduce deaths, hospitalizations, and ICU pressure in the public interest. In the event of future threats, a new mass vaccination campaign must not be implemented without taking into account the individual age; it should primarily be aimed at people over 60 and at patients of any age with immune deficits, and secondly at people over 50. COVID-19 vaccination shows a favorable benefit-risk balance in older adults, while this balance falls under the age of 40; this younger segment of population should be therefore exempt from any mandatory vaccination.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

Past research suggests a continuity between perception and memory, as reflected in influences of orienting of spatial attention by cues presented after a visual target offset (post-target cues) on target perception. Conducting two experiments, we tested and confirmed this claim. Our study revealed an elevated reliance on post-target cues for target detection with diminishing target visibility, leading to better performance in validly versus invalidly cued trials, indicative for contrast gain. We demonstrated this post-target cueing impact on target perception without a postcue response prompt, meaning that our results truly reflected a continuity between perception and memory rather than a task-specific impact of having to memorize the target due to a response prompt. We further showed an influence of attention by the post-target cues with cues presented away from a clearly visible target, meaning that visual interactions at the target location provided no better explanation of our results. Our results generalize prior research with liminal targets and confirm the view of a perception-memory continuum, so that visual target processing is not shielded against visuospatial orienting of attention elicited by events following offset of the visual target.

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.

In recent decades, large-scale forest disturbances such as windthrow and bark beetle infestations have significantly impacted the carbon balance of Earth and forest ecosystems, mainly by altering soil respiration (SR) in addition to decreased gross primary productivity. SR is considered the second highest flux on Earth, emitting 78-98 Gt C yr-1 to the atmosphere, thus contributing to global warming. Post-disturbance development is marked by changes in the size of SR. To investigate the impact of bark beetle (Ips typographus) infestations in mountain spruce forests on SR, we measured SR at infested sites by bark beetles and adjacent undisturbed stands in the High Tatra Mountains (Slovakia). The measurements were conducted during the vegetation period (May-September) in 2016 and 2017, five to six years after the initial attack by bark beetles, at an altitudinal gradient (1100-1400 m a.s.l.). SR varied throughout different months and altitudes, and we observed that SR at infested sites reached higher values (in most cases) than at uninfested stands. Average monthly and altitude SR rates during both vegetation periods showed higher values at infested sites, but not all of them were statistically significant. We observed an insignificant change in SR rate between 2016 and 2017 at both infested and uninfested sites. The highest rates of SR were observed in 2016 from July to August at both infested and undisturbed sites. On the other hand, in 2017 the highest SR rates were observed in June and July at undisturbed sites and from June to August at infested sites. However, yearly SR from May-September at infested sites showed significantly higher rates than uninfested ones in both years. SR showed a decreasing pattern with elevation gain in 2016 at infested sites. However, this pattern was not observed in 2017. Based on our observation and results we postulate that SR rates at infested sites are boosted by needle fall and debris from dead and dying trees, which increases heterotrophic SR and compensates the decrease of autotrophic SR from tree roots. This study provides important insights into the impact of bark beetle infestations on SR and highlights the need for further research on the long-term effects of forest disturbances on carbon cycling.

The possible future emergence of new SARS-CoV-2 virus variants pushes the development of new chemoprophylaxis protocols complementary to the unspecific and specific immune-prophylaxis measures currently used. The SARS-CoV-2 virus is particularly sensitive to oxidation due to the relevant positive electrical charge of its spike protein used as a ligand for target cells. The present study evaluated the safety and efficacy of a new oxidant preparation, liquid hyperoxygen (IOL), to neutralize the SARS-CoV-2 virus. IOL was incubated with throat swabs containing a human wild-type virus. The samples were then incubated with cells expressing the ACE2 receptor and therefore very sensitive to SARS-CoV-2 infection. The ability to neutralize SARS-CoV-2 was determined by assessing the amount of viral nucleic acid inside cells by PCR. The results obtained indicate that IOL, even at considerable dilutions, is capable, after incubation times of less than 30 min and even equal to 5 min, to completely inhibit SARS-CoV-2 infection. This inhibitory effect has been shown to be due to the oxidizing capacity of the IOL. This oxidizing capacity is exerted towards the virus but does not damage eukaryotic cells either in the in vitro or in the in vivo skin model. Obtained results indicate that the use of IOL, a hydrophilic liquid mixture saturated with highly reactive oxygen and nitrogen species, is a new powerful, safe, and effective tool for preventing possible future outbreaks of COVID-19 disease.

SARS-CoV-2 infection remains a global burden. Despite intensive research, the mechanism and dynamics of early viral replication are not completely understood including the kinetics of formation of genomic RNA (gRNA), sub-genomic RNA (sgRNA) and replication centers/organelles (ROs). We employed single-molecule RNA-fluorescence in situ hybridization (smRNA-FISH) to simultaneously detect viral gRNA and sgRNA, immunofluorescence to detect nsp3 protein, a marker for the formation RO, and carried out a time course analysis. We found that single molecules of gRNA are visible within the cytoplasm at 30 minutes post-infection (p.i.). Starting from 2 hr. p.i., most of the viral RNA existed in clusters/speckles, some of which were surrounded by single molecules of sgRNA. These speckles associated with nsp3 protein starting at 3 hr. p.i., indicating that these were precursors to ROs. Furthermore, RNA replication was asynchronous as cells with RNA at all stages of replication were found at any given time point. Our probes detected the SARS-COV-2 variants of concern, and BA.1 strain exhibited slower rate of replication kinetics than the WA1 strain. Our results provide insights into the kinetics of SARS-CoV-2 early post-entry events, which will facilitate identification of new therapeutic targets to early stage replication to combat COVID-19.

Background: So far, vaccination has been considered the most crucial defense against viral infection, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncology patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. Objective: This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. Material and methods: 1,668 people were observed. Over two years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in three groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. Results: The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, and colon cancer, although the response varies significantly depending on the type of cancer. Summary: The size of the humoral response and the presence of specific antibodies directed against the SARS-CoV-2, IgM, and IgG, in response to the supply of the vaccine antigen or assessed after COVID-19, is an indicator of adequate immune protection against reinfection. This study highlights for the first time the phenomenon of increased humoral response in response to a viral infection in patients with certain types of cancer that are assumed to be sensitive to oncological therapy, the initiation of which, according to generally accepted principles, was blocked by infection with the SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also seems to explain the asymptomatic course of SARS-CoV-2 infection in some of the above patients. It remains an open question to what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients.

Background: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants are dominating. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron. Recently we produced and characterized a SARS-CoV-2 vaccine based on a recombinant fusion protein consisting of hepatitis B virus (HBV)-derived PreS and two SARS-CoV-2 wild-type RBDs. Objectives: To develop a PreS-RBD vaccine which induces high levels of Omicron-specific neutralizing antibodies. Methods: We designed, produced, characterized and compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix of W-PreS-W and O-PreS-O) and chimeric (i.e., W-PreS-O) SARS-CoV-2 protein subunit vaccines. Immunogens were characterized in vitro by protein chemical methods, mass-spectrometry, circular dichroism in combination with thermal denaturation and immunological methods. In addition, BALB/c mice were immunized with aluminum hydroxide-adsorbed proteins and aluminum hydroxide alone (i.e., placebo) to study specific antibody and cytokine responses, safety and Omicron neutralization. Results: Defined and pure immunogens could be produced in large amounts as secreted and folded proteins in mammalian cells. Antibodies induced after vaccination with different doses of strain-specific, bivalent and chimeric PreS-RBD fusion proteins reacted with wild-type and Omicron RBD in a dose-dependent manner and resulted in a mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG levels induced by the different vaccines were comparable but the W-PreS-O-induced virus neutralization titers against Omicron (median VNT50: 5000) were 7- and 2-fold higher than the W-PreS-W- and O-PreS-O-specific ones, respectively and 6-fold higher than those of the bivalent vaccine. Conclusion: Among the tested immunogens, the chimeric PreS-RBD subunit vaccine, W-PreS-O, induced the highest neutralizing antibody titers against Omicron. Thus, W-PreS-O seems to be a highly promising COVID-19 vaccine candidate for further preclinical and clinical evaluation.

Background: Traumatic events adversely affect the clinical course of obsessive-compulsive disorder (OCD). Our investigation explores the correlation between prolonged interpersonal trauma and the severity of symptoms related to obsessive-compulsive and anxiety disorders. Methods: The study follows a cross-sectional and observational design, employing the International Trauma Questionnaire (ITQ) to examine areas linked to interpersonal trauma, the Hamilton Anxiety Rating Scale (HAM-A), and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to assess anxious and obsessive-compulsive symptoms, respectively. Descriptive analysis, analysis of variance (ANOVA), and logistic regression analyses were conducted. Results: We recruited 107 OCD-diagnosed patients, categorizing them into subgroups based on the presence or absence of complex post-traumatic stress disorder (cPTSD). The ANOVA revealed statistically significant differences between the two groups in the onset age of OCD (p=0.083), psychiatric familial history (p=0.023), HAM-A, and Y-BOCS (p=0.000). Logistic regression indicated a statistically significant association between the presence of cPTSD and Y-BOCS scores (p=0.000). Conclusion: The coexistence of cPTSD in OCD exacerbates obsessive-compulsive symptoms and increases the burden of anxiety. Further advancements in this field are crucial for mitigating the impact of early trauma on the trajectory of OCD and associated anxious symptoms.

Background: Brief Resolved Unexplained Events (BRUEs), formerly known as Apparent Life-Threatening Events (ALTE), are concerning episodes of short duration (typically &lt; 1 min) characterized by a change in breathing, consciousness, muscle tone, and/or skin color. In some cases, SARS-CoV-2 infection has been associated with episodes of BRUEs in previously healthy children.This study aimed to compare the demographic, respiratory, perinatal, and infectious characteristics in children affected by BRUE before the COVID-19 pandemic and after the spread of SARS-CoV-2. Methods: We conducted a retrospective observational study covering January 2018 to March 2020 (pre-COVID-19) and April 2023 (during the ongoing COVID-19 pandemic). Collected variables included clinical information during pregnancy and neonatal details of children with BRUE. Results: The number of children in the pre-COVID-19 period was 186 (41%); after the emergence and spread of SARS-CoV-2, it was 268 (59%). The risk of infection at birth for children developing BRUE was higher during the pandemic. Children were less likely to have ongoing symptomatic infection during BRUE during the pandemic (coefficient B = 0.783; p=0.009). Respiratory symptoms during BRUE were more frequent during the pandemic (coefficient B = 0.654; p=0.052). Fever during BRUE was less likely during the pandemic (coefficient B = -0.465, p=0.046). Conclusions: The study suggests that the COVID-19 pandemic has significantly impacted children with BRUE, potentially due to changes in hygiene practices and maternal-fetal infections.

One of the main challenges of the globalization became the increased destabilization and frequent economic crises. In general, managing an economic crisis is a particularly difficult task for any economy (developed or developing, and regardless the size). In the context of globalization, the process faces additional challenges. On the one hand, the world economy witnessed a shift from traditional purely economic instruments to more financial mechanisms of economic development. Indeed, the liberalization of the economy since the 1990s complicated the traditional trends of the world market development, resulting in significant fluctuation of the growth rates between different countries and regions. To respond to this evolution, governments and international organizations changed well-established strategies. For example, financial sector found itself given expanded role in economic development, with, different financial mechanisms used as key variables to evaluate an economic growth. On the other hand, the increased role of financial sector in a globilised world, increased financial relations among individual states and thus, interdependences. This “financial globalization” causes important fluctuations in the system and, as a result, causes instability in socio-economic development. Thus, an economic crisis of any important economy soon becomes a global issue (financial crisis of 2008, economic crisis of 2020).The recent global economic crisis due to the Covid-19 world pandemic, appeared to be unique for several reasons. First, it highlighted the transnational and origin-specific nature of the crisis. Second, it appeared to be the first case when non-economic factors caused a major economic crisis. As a result, this crisis turned out to be particularly difficult to predict and to manage. In this case, the main strategy of the global post-crisis rehabilitation became the restoration of the economy's predictability and ensuring its ability to obey the classical principles. According to the Organic Law on "Economic Freedom" of the European Union (2011), any factor which increases the equilibrium amount of output is reflected in the economic rehabilitation plan. Such exogenous factors are primarily fiscal mechanisms, i.e. - Reduction of taxes and increase of state expenditures. This crisis caused important structural problems with their effects on public expenditures (especially health expenditures, to the public expenditures, economic growth, price stability and budget balance) in both, developed and developing countries. Nearly every state declared an increase in public debt, inflation, and unemployment rates, while an important decrease was shown in growth rates and capital outflows. As the crisis due to the world pandemic was radically different from previous economic crises, it was difficult to manage it efficiently at the initial stage. It was complicated to forecast the scenarios of the unknown crisis with non-standard nature which was more linked to epidemiologic factors than objective economic law. The dynamics of crisis resolution depended on correct forecasting and effective implementation of global, but especially country-based reforms. More importantly, this crisis showed the important role of individual states to manage the global crisis. The traditional function of a government to ensure country’s socio-economic growth and security, increases in an extraordinary environment, such as sharp economic fluctuations and crises. In such contexts, the centralized management functions are sharply activated. The global pandemic processes have updated the economic essence of the state. The large scale of the latest economic crisis due to the world pandemic has determined the need for mutually coordinated development of anti-crisis plans of different countries. In today's dynamic landscape, modern global systems are redefining the standards and priorities of national economic policies. The economic status of countries is changing significantly as a result of their participation in these systems. As a result of these changes, today's global economy is marked by the proliferation of regionalism and the emergence of spatial economic frameworks. Thus, classical economic concepts are evolving, giving rise to a new model known as economic nationalism. This paradigm shift is generating new risks, which are increasing in severity and scope. The overriding objective of economic policy is now to ensure and predict stable development. Reflections are underway to meet the challenges of economic equilibrium and its social and institutional sustainability.In addition to the decentralization of the unified governance system, the global economy is characterized by the activation of centralized governance elements within individual countries. This requires the development of new norms for global cooperation and the careful balancing of national integration and development factors. The question of government's influence on the economy and the delegation of its powers becomes relevant once again. Effective coordination of public administration is based on the principle of decentralized government, which is a key element of a democratic model of society and facilitates the transfer of management tools to the public. The key objectives of this research are focused on the optimal distribution of state functions and the study of hierarchical principles of territorial organization within the country, fiscal mechanisms for the distribution of powers, as well as the particularities of the structuring of the spatial economy and its budgetary provisioning mechanisms.The example of the last two economic crisis showed that contemporary anti-crisis strategies should reflect several considerations. First, it becomes impossible to develop a single unified model of crisis management. Even in the context of important economic and financial globalization, the current decentralization and new spatial economic processes make it necessary to find a balance between the local priorities and global interests. Second, the role of non-economic crisis-causing factors increases compared to economic determinants. That is why international and country-based reforms should aim at not only economic rehabilitation, but also on the social, cultural and environmental restorations. Third, it becomes difficult to correctly predict the consequences of the crisis and thus, the effects of the anti-crisis strategy. Consequently, the success of the post-crisis rehabilitation of the countries' economies depends significantly not only on the effective realization of their own plan, but also, in general, on the specificities of the global economy and on the ability of the world markets to overcome the negative consequences of a crisis. In this context, the development of complex post-crisis platforms and state post-crisis strategies is the priority. The most effective component in the anti-crisis strategy is the monetary instruments of economic management. As for the determinant of successful functioning of economy, the priority should be given to the regulation of exchange rate, interest rate and inflationary processes. A state anti-crisis programs should reflect the crisis prevention strategy, which, on its turn, should differentiate the economic functions of the state and crisis management mechanisms according to the specific trends of given processes. It should aim at gaining stable development of the economy. Additionally, an anti-crisis plan should reflect the role of the society in the development process and its mental changes under crisis conditions. The state should be responsible for establishing and monitoring anti-crisis management mechanisms, financial recovery of the country and formation of correct relations. It is especially important to ensure economic security, to stabilize the development process and standard of living, to support the private sector and small entrepreneurship, to increase economic freedom, to ensure effective distribution of labor and capital, and others. All strategies of the anti-crisis platform should be focused on social results, as it should contribute to a fair distribution of income and to poverty reduction.

Abstract: (1) Background: Post-COVID syndrome is defined as symptoms that occur simultane-ously with or after COVID-19 infection, last for 12 weeks, and are not due to another diagnosis. Limited data are available on people’s long-term quality of life (QoL) following COVID-19 infection. The aim of this cross-sectional study was to investigate long-term QoL after COVID-19 among employees of the St. Josef Hospital in Paderborn, Germany, and to identify risk factors. (2) Methods: A monocentric, cross-sectional study was conducted using the validated and digitized WHOQOL-BREF questionnaire via Netigate® between 10/2022 and 02/2023. Data on QoL and global health status were collected in the following four domains: physical health, mental health, social relationships, and environment. (3) Results: The response rate was 73.84% (923/1250). Furthermore, 63.45% of hospital staff respondents reported at least one persistent symptom after COVID-19 infection, leading to significant differences in QoL. Pre-existing conditions, persistent symptoms, and disability after COVID-19 infection, as well as high BMI, no partnership, and low educational level were found to significantly contribute to long-term low QoL. (4) Conclusions: Obesity, lack of partnership, and a low level of education were independent risk factors for lower QoL post-COVID-19 infection in this cohort of hospital staff. Further multicenter studies are re-quired to validate the incidence and their suitability as independent risk factors for post-COVID syndrome.

Background and aims: For many surgical procedures, spinal anesthesia is a reliable and efficient anesthetic approach. Numerous drugs have been reported to be administered to intrathecal local anesthetics as adjuvants to increase the efficacy of spinal anesthesia. There is little evidence of the effect of intrathecal dexmedetomidine on pain scores and the consumption of analgesia postoperatively. Methods: After obtaining ethical approval, demographical and clinical data of patients who underwent surgical procedures under spinal anesthesia with intrathecal dexmedetomidine or fentanyl was collected and analyzed. Results: In this study with 96 patients, intrathecal dexmedetomidine (group D) resulted in significantly lower post-operative pain scores compared to intrathecal fentanyl (group F) (p=0.000). Across various surgical types, including Orthopedic, General, Urology, and Obs/Gyne procedures, group D consistently displayed reduced pain scores (p&lt;0.001). The number of patients who needed post-operative analgesia was significantly higher in group (F) than in group (D) (40 vs 23, p=0.002). Conclusion: Compared to fentanyl, intrathecal dexmedetomidine as an adjuvant to local anesthesia was found to lower post-operative pain scores and decrease the need for post-operative analgesia.

Clothing consumers mostly purchase, use, and dispose of clothing products in a linear business model. This approach pollutes the environment and causes economic and social crises in the ecosystems. This study evaluates the amount of generated postconsumer clothing waste (PCCW) and proposes recycling as a sustainable waste management approach. Data were collected to understand disposal behavior of consumers with 474 respondents selected from households in Bahir Dar city. The findings show that all the determinant factors on the PCCW generation level except religion were significant. The most frequently disposed type of clothing waste is jeans-trouser (51%). The CEBM was used to develop alternative products from a jeans-based clothing waste. The jean's fiber and fabric-reinforced composite materials were developed using unsaturated polyester resin as a sustainable way of PCCW management strategy. The shredded form fiber-reinforced composite was found to have a smoother surface than that of the chopped or cut fabric-reinforced composite. The product was characterized by physical and mechanical properties. The study can be further extended to the scope of the entire consumers in Ethiopia and alternative recyclable products can be studied.

Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions and although they have been associated with obesi-ty-comorbidities, their protein cargo in this context remain largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma derived EVs from diet induced obese murine models. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein folding functions, highlighting the importance of proper folder in maintaining metabolic homeostasis. Previously, we revealed that gut derived EVs proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein post-translational modifications in the intricate mechanisms underlying obesity, shed-ding light on potential biomarkers and pathways for future research.

Covid-19 is an airborne disease, with the vast majority of infections occurring indoors. By comparison, little transmission occurs outdoors. Here, we investigate the airborne transmission pathways that differentiate the indoors from outdoors, and conclude that profound differences exist, which help to explain why SARS-CoV-2 transmission is much more prevalent indoors. Near and far-field transmission pathways are discussed along with factors that affect infection risk, with aerosol concentration, air entrainment, thermal plumes, and occupancy duration all identified as being influential. In particular, we present the fundamental equations that underpin the Wells-Riley model, and show the mathematical relationship between inhaled virus particles and quanta of infection. A simple model is also presented for assessing infection risk in spaces with incomplete air mixing. Transmission risk is assessed in terms of aerosol concentration using simple 1D equations, followed by a description of thermal plume-ceiling interactions. With respect to this, we present new experimental results using Schlieren-visualisation and Computational Fluid Dynamics (CFD) based on the Eulerian-Lagrangian approach. Pathways of airborne infection are discussed, with the key differences identified between indoors and outdoors. In particular, the contribution of thermal and exhalation plumes is evaluated, and the presence of near-field/far-field feedback loop postulated, which is absent outdoors.

Human-to-animal SARS-CoV-2 transmission was observed, including a veterinarian contracting COVID-19 through close contact with an infected cat, suggesting an atypical anthropozoonotic transmission. This study investigated the prevalence of SARS-CoV-2 antibodies in cats during human outbreaks and elucidated the correlation between cat infections and human epidemics. A total of 1,107 cat sera samples were collected and screened for SARS-CoV-2 antibodies using a modified indirect ELISA human SARS-CoV-2 antibodies detection kit. The samples were confirmed using a cPass surrogate viral neutralization assay. The SARS-CoV-2 seropositivity rate was 22.67% (199/878), mirroring the trend observed in concomitant human case numbers. The waves of an epidemic and provinces did not significantly impact ELISA-positive cat. Notably, Chon Buri ex-hibited a strong positive correlation (r = 0.99, P = 0.009) between positive cat sera and reported human case numbers. Additionally, cPass surrogate viral neutralization revealed a 3.99% (35/878) seropositivity rate. While there were significant differences in positive cat numbers and proportions between epidemic waves. In Samut Sakhon, a positive correlation (r = 1, P = 0.042) was noted between the proportion of positive cat sera and reported human cases. The findings emphasize the need for ongoing surveillance to comprehend SARS-CoV-2 dynamics in both human and feline populations.

The COVID-19 pandemic has led to a substantial revolution in the incorporation of digital solutions in healthcare. This systematic review investigates the enduring physical and psychological consequences individuals experience up to two years post-recovery. Additionally, it focuses on examining the influence of mHealth interventions on these effects. Significantly, 41.7% of survivors experience lingering symptoms that have not been addressed, while 14.1% encounter difficulties in returning to work. The presence of anxiety, compromised respiratory functioning, and persistent symptoms highlight the immediate requirement for specific therapies. Telehealth, particularly telerehabilitation, presents itself as a possible way to address these difficulties. The study thoroughly examines 10 studies encompassing 749 COVID-19 patients, investigating the efficacy of telerehabilitation therapies in addressing various health markers. Telerehabilitation-based breathing exercises yield substantial enhancements in functional performance, dyspnea, and overall well-being. The results emphasize the potential of telerehabilitation to have a favorable effect on patient outcomes, however more research is needed to strengthen the existing evidence basis as one of the most important limitation is the limited number of trials and the evaluation of varied therapies. The analysis highlights the significance of digital solutions in post-COVID care and calls for ongoing research to improve comprehension and implementation of telehealth interventions in a swiftly changing healthcare environment.

Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

Research indicates compelling evidence of SARS-CoV-2 vertical transmission as a result of placental pathology. Background: This study offers an approach on histopathological and immunohistochemical placental observations from SARS-CoV-2 positive mothers compared negative ones. Methods: Out of 44 examined placentas, 24 were collected from patients with SARS-CoV-2 infection during pregnancy and 20 without infection. Results: The disease group showed strong SARS-CoV-2 positivity of the membranes, trophoblast and fetal villous macrophages. Most infections occurred during the third trimester of pregnancy (66.6%). Pathology revealed areas consistent with avascular villi (AV), thrombi in the chorionic vessels and umbilical cord in the positive group, suggesting fetal vascular malperfusion (FVM). Other observed features included infarction (17%), perivillous fibrin deposition (29%), intervillous fibrin (25%), delayed placental maturation (8.3%), chorangiosis (13%), chorioamnionitis (8.3%) and meconium (21%). The negative control group revealed only one case of placental infarction (5%), intervillous fibrin (5%), delayed placental maturation (5%), chorioamnionitis (5%) and two cases of meconium (19%). Our results were consistent with literature. Conclusions: This study shows SARS-CoV-2 has an impact on coagulation, demonstrated by fetal thrombotic vasculopathy (p=0.01) and fibrin deposition (p=0.01). Further research is necessary to establish whether SARS-CoV-2 is the cause of vascular pathologies during pregnancy.

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of an ongoing, open-label, phase 2/3 study of monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy, participants ≥12 years old (N=412 [12‒17 years, N=30; 18‒55 years, N=174; >55 years, N=208]) who previously received ≥3 doses of a US-authorized mRNA vaccine, the most recent being an Omicron BA.4/BA.5-adapted bivalent vaccine ≥150 days before study vaccination, were vaccinated. Serum 50% neutralizing titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 were measured 7 days and 1 month after vaccination in a subset of ≥18-year-olds (N=40) who were positive for SARS-CoV-2 at baseline. Seven-day immunogenicity was also evaluated in a matched group who received bivalent BA.4/BA.5-adapted BNT162b2 in a previous study (NCT05472038). There were no new safety signals; local reactions and systemic events were mostly mild to moderate in severity, adverse events were infrequent, and none led to study withdrawal. The XBB.1.5-adapted BNT162b2 induced numerically higher titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 than BA.4/BA.5-adapted BNT162b2 at 7 days and robust neutralizing responses to all 3 sublineages at 1 month. These data support a favorable benefit-risk profile of XBB.1.5-adapted BNT162b2 30 μg. NCT05997290

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single dose rifampicin post exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, a SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases both retrospectively (2010-2017) and prospectively (2018 onwards). We conducted a retrospective audit to determine comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,643 household contacts were identified (9,791 in the retrospective and 3,850 in the prospective cohort). In the retrospective cohort, 1,044 (11%) contacts were absent, 403 (4%) were ineligible for SDR and 42 new cases were detected (0.4%) Overall SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were a total of 23 SDR refusals. The median time to SDR ad-ministration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts respectively. SDR was readily accepted in both cohorts. The new case detec-tion rate (0.5%) is consistent with that seen in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

The emergence of SARS-CoV-2 subvariant BA.2.86, also known as Pirola, has raised concerns about its transmissibility, virulence, and immune escape. The aim of this letter is to address the current evidence on the origin, spread, and characteristics of Pirola, and discuss its implications for public health and vaccine development. The need for enhanced surveillance, genomic sequencing, and epidemiological studies to monitor the evolution and impact of Pirola and other SARS-CoV-2 variants are highlighted in this letter along with the importance of global cooperation and coordination to prevent and control future outbreaks of this novel coronavirus strain.

(1) Background: Bats are reservoirs and vectors of significant zoonotic diseases. Our study focuses on understanding the role of bats as reservoirs and carriers of coronaviruses, given their epidemiological significance and the recent global health crises stemming from coronavirus outbreaks. (2) Methods: We conducted virological screening of bats hibernating in military bunkers at the Natura 2000 site "Nietoperek" in Western Poland. This involved collecting and analyzing oral and anal swab samples from 138 bats across six species, using a combination of pan-coronavirus and SARS-CoV-2 specific PCR assays. (3) Results: Out of 138 bats, only one anal swab tested positive for coronavirus. However, we were not able to obtain genomic sequence from the sample. No SARS-CoV-2 was detected in any of the samples. The low prevalence of coronavirus in the studied colony contrasts with higher rates found in other regions and may be influenced by the physiological and behavioral conditions of bats during hibernation. (4) Conclusions: Hibernating bats may show a low prevalence of coronavirus, potentially due to the hibernation process itself. This finding indicates that hibernating bats may not be the most optimal subjects for screening zoonotic pathogens. However, continuous monitoring of bat populations for emerging and reemerging diseases is recommended for a comprehensive epidemiological understanding.

Post-earthquake fire is considered as a catastrophic secondary disaster to personal and property safety. In this article, an evacuation assessment of a complex rail transit station under the post-earthquake fire for sustainable buildings was conducted from the internal environment and external rescue based on Building Information Modeling (BIM) and Fire Dynamic Simulation (FDS). The internal environment evacuation assessment simulation experiments were conducted in six hypothetical high-risk scenarios. Besides, the external rescue assessment was based on investigation of the route and the rescue time required during different periods of holidays and workdays. The results show that: (1) The influence caused by different size of fire area in the power distribution room is smaller than those in the train at the platform floor. (2) In the case of fire scenarios with the same fire area but different fire locations, the impact on temperature is greater than that on CO concentration in power distribution room. (3) It shows slight differences between single-floor fire and double-floor fire on evacuation of small area fire in power distribu-tion room. Meanwhile, optimized design recommendations are proposed to reduce the risk of emergency evacuation in both internal and external environments of rail transit stations for sustainable future buildings.

Mechanical properties of three-dimensional (3D) printed resin can be improved by decreasing oxygen concentrations during post-curing, and nitrogen saturated post-curing has been applied for the purpose. This study aimed to evaluate and compare the color stability of 3D printed resin crowns post-cured in normal air and nitrogen saturated conditions. Crowns were fabricated with 3D printer and post-cured in normal air (control group; air) or nitrogen saturated condition (experimental group; nitrogen). The specimens in each group were subdivided into four subgroups, each exposed to different discoloration agents: distilled water, coffee, wine, and curry. Post-immersion color changes were measured using a digital spectrophotometer and analyzed through repeated measures ANOVA. Fourier Transform Infrared (FT-IR) spectroscopy evaluated the degree of conversion of resin over immersion times for both post-curing conditions. Comparing the effects of post-curing conditions, significant difference was found between control and experimental groups over immersion time in wine and curry subgroups. In FT-IR analysis, there was significant difference in degree of conversion between the air and nitrogen groups from 10 to 300 seconds. The findings suggest that nitrogen saturated post-curing can potentially enhances the conversion rate of 3D printed resin crowns, thereby improving their color stability.

Severe acute respiratory syndrome coronavirus 2 infects many people, but many infected individuals do not develop symptoms. COVID-19 is an inflammatory disease that affects a portion of individuals infected with the virus, and it is associated with liver injury and other complications leading to hospitalization, critical illness, and death. Remdesivir is an antiviral agent used for treatment of hospitalized patients with COVID-19 to improve time to recovery, reduce duration of mechanical ventilation, decrease the need for supplemental oxygen, and decrease the risk of mortality. Remdesivir-associated hepatotoxicity has been observed as increased transaminases more than 5 times the upper limit of normal in hospitalized patients with COVID-19 but causality has not been proven. It is generally difficult to distinguish between remdesivir-associated hepatotoxicity and COVID-19-induced hepatotoxicity. The purpose of this review is to evaluate the evidence for remdesivir-associated hepatotoxicity. Current evidence suggests that elevated liver enzymes in hospitalized COVID-19 patients are more likely to be due to the infection than remdesivir and that a 5-day course of remdesivir seems to be safe in regards to hepatotoxicity.

Objective: Spontaneous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA vaccination causes a marked increase in antibody titer because of the combined effect of vaccine and infection (“hybrid immunity”). In this study, we discuss the significance of the mRNA vaccine booster inoculation that has been repeatedly performed in Japan.Methods: We describe the temporal trends of antibody titers in cases in which antibody titers were markedly increased by hybrid immunization.Results: The antibody titer increased with hybrid immunization and tended to decrease with time. However, several cases maintained high antibody titers for approximately one year after coronavirus disease 2019 (COVID-19 diagnosis), even without booster vaccination.Conclusions: Most Japanese patients naturally infected with COVID-19 were infected after mRNA vaccination, and many maintained high antibody titers due to hybrid immunity. The significance of additional vaccination in hybrid-immunized cases is highly questionable regarding cost-effectiveness and risk-benefit.

During the last decades, a growing number of studies have shown that infections during pregnancy have an important impact on both pregnant women and their fetuses. Our goal was to identify newborns from pregnancies with SARS-CoV-2 infection and to investigate the extension of neonatal complications using cardiac, abdominal and cerebral ultrasonography, hearing testing and indirect ophthalmoscopy. By contrast, neonates whose mothers were vaccinated against COVID-19 during pregnancy and those from pathology-free pregnancies have been examined. A total of 458 newborns were included, over a period of 10 months, divided into 3 groups, COVID-19 group, vaccine group and control group. Although 6 cardiac malformations were found in the COVID-19 group, no correlation was made compared to the vaccine and control group (p=0.07). Grade 1 intraventricular hemorrhage and hypoxic ischemic encephalopathy were the most prevalent among neonates from mothers with SARS-CoV-2 infection (p=0.002 and p&lt;0.001, respectively). The kidney anomaly found to be most frequent in this group was grade 1 unilateral hydronephrosis (p&lt;0.001). COVID-19 disease during the gestational period had no effect on the auditory or visual function. Despite the fact that our observations are relevant, further studies investigating the effects of SARS-CoV-2 infection during pregnancy and the neonatal outcomes are necessary.

The success of Toxoplasma gondii (intracellular parasite) host cell invasion relies on the apical complex, a specialized microtubule cytoskeleton structure associated with secretory organelles. The genome encodes three isoforms of both α- and β-tubulin which are altered by specific post-translational modifications (PTMs), changing the biochemical/biophysical proprieties of microtubules, and modulating their interaction with associated proteins. Tubulin PTMs are a powerful and evolutionarily conserved mechanism to generate tubulin diversity, forming a biochemical ‘tubulin code’ that can be ‘read’ by microtubule-interacting factors. The T. gondii tubulin PTMs are: α-tubulin acetylation, α-tubulin detyrosination, Δ5α-tubulin, Δ2α-tubulin, α- and β-tubulin polyglutamylation, and α- and α-tubulin methylation. Tubulin glutamylation is a key candidate to assist microtubule remodeling in Toxoplasma, being involved in the regulation of microtubule stability, dynamics, interaction with motor proteins, and severing enzymes. The correct balance of tubulin glutamylation is achieved by the coordinated action of polyglutamylases and deglutamylating enzymes. In this work we will review and discuss the current knowledge on T. gondii tubulin glutamylation. By in silico identification of mammalian protein orthologs we explored and updated the identification of putative proteins related to glutamylation, contributing to a better understanding of the role of tubulin glutamylation in T. gondii.

Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection, however no clinical trial data are available and combined use of direct acting antivirals (DAA) and monoclonal antibodies (mAb) has been reported only anecdotally. To assess the cooperative effects of dual drug combinations in vitro, we used a VERO E6 cell based in vitro system with the ancestral B.1 or the highly divergent BQ.1.1 virus to test pairwise combinations of the licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) and the active metabolite of molnupiravir (EIDD-1931) as well the combination of RDV with four licensed mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested only with the susceptible B.1 virus). According to SynergyFinder 3.0 summary and weighted scores, all the combinations had an additive effect. Within DAA/DAA combinations, paired scores with the B.1 and BQ.1.1 variants were comparable. In the post-hoc analysis weighting synergy by concentrations, several cases of highly synergistic scores were detected at specific drug concentrations, both for DAA/DAA and for RDV/mAb combinations. This was supported by in vitro confirmation experiments showing a more than linear shift of a drug effective concentration (IC50) at increasing concentrations of the companion drug, although the effect was prominent with DAA/DAA combinations but minimal or null with RDV/mAb combinations. These results support a cooperative effects of dual drug combinations in vitro, which should be further investigated in animal models before introduction into the clinic.

(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: Recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects. (3) Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time. (4) Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.

Coronaviruses are a large family of diverse enveloped RNA viruses found in numerous animal species. They are well-known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in human populations. In contrast, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we discuss the significance and perspectives of broad-spectrum therapeutics and vaccines.

The SARS-CoV2 Pandemic affected the global epidemiology of respiratory infections, including Respiratory Syncytial Virus (RSV), thanks to state governments’ implementation of mitigation strategies, like the promotion of face masks and lockdowns. However, after the Pandemic, the dramatic resurge of these diseases was reported worldwide. Our retrospective study, involving three Spoke Pediatric Departments, includes all the infants under one year of age hospitalized for RSV bronchiolitis in a period before the Pandemic period (2017-2020), during the SARS-CoV2 Pandemic (2020-2021) and after the Pandemic (2021-2023). The primary aim was to analyse the temporal trend of RSV in the three periods. Then, clinical and epidemiological characteristics were analysed to highlight clinical differences in the patients affected, in the severity of the in-fections and in the short-term outcomes. Ultimately, we analysed the RSV prevalence in the global bronchiolitis hospitalization in the same over reported periods. Overall, we included 237 patients. Before the Pandemic, the peak was recorded in January and February while after the Pandemic, the peak was in November and December. A higher prevalence of RSV was demon-strated after the Pandemic compared to the period before the Pandemic; no difference in severity was reported overall. In conclusion, an increase in RSV cases after the Pandemic has been demonstrated with an anticipated peak, while no differences were recorded in severity.

Background: To describe epidemiological characteristics and perform a SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo state. Methods: During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value and variants lineages. Results: An increase in the number of SARS-CoV-2 positive cases until the fourth epidemiological week were observed. From the 4th epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a growing increase in SARS-CoV-2 infection within the age group 0-10 throughout the epidemiological weeks, from 2.8% in the 1st epidemiological week to 9.2% in the 8th epidemiological week. We further observed significantly higher Ct values within younger patients samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%) and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sublineage by that time. Our results suggest the initial dissemination steps of the Omicron’s sublinage BA.2 into the younger group, due specific genomic features of the detected sequences. Conclusion: These data provide interesting results related to the spread, emerging and evolution of the Omicron variant in the Southeast Brazilian population.

Knowledge of post-larval swordfish (Xiphias gladius) ecology in the world’s oceans is incomplete as they are rarely found in ichthyoplankton samplings or commercial catches and individuals are difficult to observe in the marine ecosystem. Analyses of stomach contents of apex predators can provide otherwise unobtainable ecological insights. Two well-preserved bills of post-larval swordfish were identified among the partially digested stomach contents of an adult male dolphinfish (Coryphaena hippurus) caught in the northern Tyrrhenian Sea. The lower jaw to fork lengths of the two predated swordfish were estimated at respectively, 18 and 22 cm, corresponding to 81- and 99-day-old swordfish hatched in the 2022 spawning season. This analysis and recent information on the reproductive dynamics of swordfish in the same area reported in the literature shed light not only on the early stages of swordfish growth but also on dolphinfish ecology in the Tyrrhenian Sea. The two species share the same habitat and are both caught with commercial pelagic surface longlines. Environmental shifts associated with climate change could unpredictably modify the reproduction dynamics, growth, recruitment and distribution of both species. This knowledge is important for the sustainable management of regional fisheries.

The study evaluated the immune response to the Janssen Ad26.COV2.S COVID-19 vaccine in a Ugandan cohort, focusing on spike (S) and nucleocapsid (N) protein-directed antibodies. The aim was to assess the longevity and robustness of the elicited antibodies, aligning with breakthrough infections and prior exposure to SARS-CoV-2. The study involved 319 specimens collected over 12 months from 60 vaccinees aged 18 to 64. Binding antibodies were quantified using a validated ELISA method to measure SARS-CoV-2-specific IgG, IgM, and IgA levels against the S and N proteins. The results showed that baseline seropositivity for S-IgG was high at 67%, increasing to 98% by day 14 and consistently stayed above 95% for up to 12 months. However, S-IgM responses remained suboptimal. An increased S-IgA serpositivity rate doubled from 40% at baseline to 86% just two weeks following the initial vaccine dose, indicating sustained and robust mucosal immunity. An increase in N-IgG levels at nine months post-vaccination suggested breakthrough infections in eight cases. Baseline cross-reactivity influenced spike-directed antibody responses, with those with pre-existing S-IgG antibodies showing higher responses. The vaccine demonstrated robust and long-lasting immune responses, with significant implications for regions where administering follow-up doses is challenging.

COVID-19 was an inflammatory pneumonia caused by a respiratory infection with a coronavirus named SARS-CoV-2. Severely ill COVID-19 patients could die of acute pulmonary and systemic inflammation. Thus, there was a theory that long COVID-19 shared many similarities with systemic autoimmune diseases. There was also a theory that the SARS-CoV-2 virus could infect many cell- and tissue-types distributed throughout multiple organ systems of the body. I aim to review the above theories using unbiased high-throughput datasets cataloguing gene expression. Studies reviewed used the technology of next generation sequencing, either as bulk tissue RNA sequencing, or as single-cell RNAs sequencing; ingenious methods for signal deconvolution were then used to identify individual cell types. Datasets reviewed suggested that severe COVID-19 induced expression of genes associated with pro-inflammatory signaling, tissue development or remodeling, scarring, or cell death. The datasets also provided evidence for several inflammatory syndromes associated with COVID-19, such as neuronal COVID, acute respiratory disease syndrome, vascular inflammation, or multisystem inflammatory syndrome. Indeed, inflammatory signal during severe COVID-19 was reported in many cell types, for example in structural cells, in infiltrating immune cells, in the vascular system, or in circulating cells in the blood. There was also frequently a change in proportions of immune cell-types in the blood, epithelial cells in the lungs, or among infiltrating immune cells.

The Hollow fiber membrane contactor (HFMC) is an intensification process that combines membrane and absorption technologies, being a technology in expansion, so the dynamics of this process is crucial for an increase in industrial scale-up. In this manuscript a rigorous dynamic model of an HFMC is developed and simulated in Python software for the absorption of post-combustion CO2 using a monoethanolamine (MEA) solution, which was validated using available data in literature in steady state. Dynamic simulations were performed to analyze the model's capability to predict the effect of disturbances on the responses of CO2 capture ratio and loading. Four distinct experiments were conducted by step changes and pulse disturbances at the following variables: gas and liquid volumetric flow rates, CO2 composition in flue gases, and CO2 lean load. The gas phase showed a faster response compared to the liquid. The CO2 capture ratio and rich loading presented opposite responses when disturbing both liquid flows, and for the composition and lean loading variations, the capture ratio presented an inverse response characteristic, while the loading showed a delayed response. As the model proved to be capable of returning to the reference state, it can potentially be used for control studies purposes.

This article presents a narrative review of neonatal and paediatric complications in post-dated pregnancy and covers scientific views on the aetiology, pathology, risk factors, symptoms and complications of post-dated pregnancy. A pregnancy extending beyond 42 weeks of gestation is termed as a post term pregnancy. There are multiple complications that can occur in the perinatal period, some of the most common ones are stillbirth, asphyxia, meconium aspiration syndrome, fetal distress syndrome, etc which are found to be greater in post-dated pregnancy and hence ultimately leads to increased mortality and morbidity of the new born. Studies have shown that post-term pregnancy also causes increased risk of developing behavioural and emotional problems in children of paediatric age group. It is surprising not much importance has been given to the maternal and neonatal consequences of post- term pregnancies. It is not well understood why some women experience post-dated pregnancies. It is found that factors such as hormones and genetic build up, are responsible for causing post-term pregnancy in an obese female. The treatment and management of a post-term pregnancy still poses a challenge to clinicians in determining the right choice and right time for a particular intervention so that both mother and fetus can be prevented from having complications.

Studies report variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID-19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes. In addition, sex hormones have complex regulatory mechanisms that affect the immune response to viruses. These hormones also affect metabolism through obesity, and severe disease can result from complications such as thrombosis. This review presents the latest research on the regulatory functions of hormones in viral receptors, immune responses, complications as well as their role in COVID-19 progression. It also discusses the therapeutical possibilities of these hormones by reviewing the recent findings of clinical and assay studies.

Several methods can be used to evaluate antibody avidity, one of which is the modified ELISA, in which a chaotropic agent is added to disrupt the binding between the antigen and the antibody. Although the avidity index provides relevant information about the functionality of antibodies, it does not allow us to characterize which antigens the antibodies are strongly bound to. To this end, we adapted the Immunoblot and Dot-Blot techniques by adding potassium thiocyanate (KSCN) after incubating nitrocellulose membranes with serum from mice immunized with Neisseria meningitidis outer membrane vesicles (OMVs) or serum from mice immunized with recombinant receptor-binding domain (RBD) of SARS-CoV-2, with different adjuvants for each antigen. In terms of results, when standardizing the incubation time of sera with KSCN, we observed that 5 minutes was the ideal time for both assays, however, when using different dilutions of serum from mice immunized with RBD, there was an influence on the strength of antigen-antibody binding. For the N. meningitidis assay, the antibodies maintained high avidity for the antigens present in the OMVs, PorA, NadA, and Opa, especially in the presence of the aluminum hydroxide adjuvant. The research showed that standardizing the Immunoblot and Dot-Blot in the same assay optimizes time and resources, allowing qualitative analysis for two different antigens, and resulting in more robust information for immunization studies against these pathogens.

(1) Background: Non-surgical endodontic treatment has been repeatedly shown to be clinically successful, however, clinical data are scarce. This practice-based retrospective clinical study aimed to investigate endodontic outcome over 40 years and to identify relevant factors from clinical protocols. (2) Methods: Two experienced dental practitioners in two different private dental practices treated 174 patients with 243 teeth from 1969 to 1993. After obturation, either a new restoration (amalgam, resin composite, glass-ionomer cement), or re-cementation of pre-existing prosthetic restorations or its renewal followed. Metal posts (operator A) or screws (operator B) were inserted when indicated. The primary outcome (tooth survival) was achieved when the endodontically treated tooth was in situ, painless and in full function. Secondary outcome was to investigate the impact of potential prognostic factors on survival rates. (3) Results: Overall mean 40-years survival was 56.1% of all treated teeth after 40 years of clinical service resulting in an annual failure rate of 1.1%. Most investigated clinical factors (Jaw, tooth position, number of intracanal dressings, post/screw placement, sex) had no significant influence on survival. Among postendodontic restorations, resin composite was advantageous. (4) Conclusions: Even with materials and techniques from the 1970’s and 1980’s, successful root canal treatment was achievable. Except postendodontic restorations, most of the evaluated factors had no significant influence on clinical long-term survival of root-canal treated teeth.

Long Covid or post-acute sequelae of SARS-CoV-2 infection (PASC) can manifest as long-term symptoms in multiple organ systems, including respiratory, cardiovascular, neurological, and metabolic systems. In patients with severe COVID-19, immune dysregulation is significant, and the relationship between metabolic regulation and immune response is of great interest in determining the pathophysiological mechanisms. We aimed to characterize the metabolomic footprint for recovering severe COVID-19 patients in three consecutive time points and compare metabolite levels to controls. Our findings add proof of dysregulated amino acid metabolism in the acute phase, and dyslipidemia, glycoprotein level alterations, and energy metabolism disturbances in severe COVID-19 patients 3-4 months post hospitalization.

A change in biological properties of the SARS-CoV-2 virus can enhance its transmissibility and virulence, complicate the disease course, and reduce the effectiveness of anti-viral therapy and vaccination. We have studied 16 genetic lineages of the Omicron variant. The viral reproduction course was analyzed based on plaque morphology in the agar layer and the maximum titer in Vero E6 cells. BALB/c mice and Syrian hamsters were used as animal models. Viral load and infectious SARS-CoV-2 titer were determined in the nasal tissue and lungs. The severity of infectious process was assessed using histological methods. An increased plug size was observed in CH.1.1 and BQ.1.2.1 strains after six passages. This was due to substitutions D614G, H655Y, and N764K in the coronavirus S protein. The same changes in gene variants Gamma and BA.1 were caused by the substitution R682W, which is not present in lineages CH.1.1 and BQ.1.2.1. A similar substitution, namely R682P, was observed in the BA.5.1 strain. We characterized BA.1 (as a reference), BA.5.2, and XBB.3 strains in vivo as representatives of the main circulating genetic lineages. For the BA.1 strain, ID50 was 1.3 and 14 TCD50 in Syrian hamsters and BALB/c mice, respectively. An insignificant increase in the BA.5.2 virulence compared to that of BA.1 was noted (ID50 was 07. and 10 TCD50, respectively). The XBB.3 pathogenicity in laboratory animals is similar to that of BA.1 (ID50 was 1.8 and 15 TCD50, respectively). Experiments showed a consistent decrease in the virulence of Omicron strains compared to previously circulating SARS-CoV-2 variants. A co-evolutionary change in amino acid sequences, affecting the conformation of the coronavirus S protein and its surface epitopes in representatives of different genetic lineages, was noted. The emergence of potential proteolysis sites and alterations of the furin cleavage site have been observed in numerous Omicron coronavirus variants.

Non-coding RNAs, specifically microRNAs (miRNAs), exhibit altered expression and contribute significantly to the pathological processes observed in numerous diseases, encompassing various types of human cancers. Recent discoveries regarding miRNAs underscore their crucial roles in tumor pathogenesis and their responses to diverse therapeutic interventions. miRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in the miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive target genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many types of cancers functioning as either oncomiRs or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer. Profiling deregulated miRNAs in many cancer types has been shown to correlate with disease diagnosis, indicate optimal treatment options, and predict response to a specific therapy. Specific miRNA signatures can track all stages of disease including many cancer types and hold potential as biomarkers and therapeutic targets as well as therapeutics as miRNA mimics and inhibitors (antagomirs). As such, identifying specific miRNAs and mRNAs they regulate in many types of cancer along with downstream pathways can be used as potential therapeutic targets. Because a single miRNA can regulate a pool of targets involved in similar cellular processes and pathways, thereby amplifying the cellular response, this potentially makes miRNAs powerful therapeutics to restore cell functions that are altered as part of a disease phenotype. However, because a single miRNA regulates multiple gene expressions their cellular effects are numerous leading to potential off-target effects. Besides their intended targeting issues, there is a need to reduce the immunogenic reactions and determine the minimal dosing to achieve the desired effect while minimizing side effects. As such, a careful risk evaluation of miRNA therapeutics is needed to minimize off-target effects and to avoid overdosing of miRNA drugs. Furthermore, a limited understanding and validation of the specific roles of miRNAs limits their clinical application. In addition, there are many challenges concerning the delivery, sensitivity, specificity, toxicity, and applicability of the potential utility of miRNAs as therapeutic targets or therapeutics. Thus, future work will warrant if miRNAs can be used as cancer biomarkers as well as therapeutics for clinical application.

The COVID-19 pandemic necessitated a profound shift to online education, impacting students across various educational levels. This research, drawing from a comprehensive survey of 1,000,000 students, delves into the surge in demand for online education during the pandemic and its potential enduring implications. The study scrutinizes factors steering this transition, the perceived effectiveness of online education, challenges encountered by students, and their anticipated preferences for the future. Results unveil nuanced perspectives among K-12, undergraduate, and postgraduate students, with safety, flexibility, and accessibility emerging as pivotal influencers. The findings offer valuable insights into challenges faced and future preferences, enlightening educational stakeholders about the dynamic needs of students and contributing to the ongoing evolution of the post-pandemic educational landscape.

background: The Islamic Republic of Iran has been under sanctions since 1979. These sanctions were further reinforced between the years 2005 and 2012. This study utilizes available data from Iran post-sanctions to review the impact of economic sanctions on both the mental health and the quality of life of Iranian citizens.Methods: A comprehensive scoping review was conducted to identify studies examining the impact of sanctions on health in Iran. Searches were initiated in 2012 using PubMed/Medline, Embase, Web of Science, Scopus, and the Scientific Information Database (Iranian Database) with keywords such as sanctions, implications, mental health, quality of life, civilian mental health, and Iran. Subsequent to the screening process, secondary reports and letters to the editor were excluded. Only original studies—those collecting data via observation, interviews, surveys, experiments, or literature reviews—were retained for analysis. In addition to these search strategies, reference scanning was undertaken to identify additional articles pertinent to the scope of the current study. This thorough approach facilitated the discovery of relevant and significant articles exploring the effects of sanctions against Iran on the mental health and overall well-being of its civilian population. Following the search, duplicate articles were meticulously identified and removed by the authors. Data were subsequently extracted and summarized, focusing on study characteristics and the observed effects of sanctions on civilian mental health and quality of life in Iran.Result: Out of 165 items identified in the preliminary search, ten articles met the inclusion criteria. These selected articles highlighted the pronounced effects of sanctions on various health-related domains.Conclusion: Since 2012, Iran has been subject to intensified sanctions. There is evidence to suggest that the economic sanctions, imposed by Western nations, and have exerted a negative and detrimental impact on the health of individual Iranians.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) utilizes Angiotensin Converting Enzyme 2 (ACE2) as its main receptor for cell entry. We have bioengineered a soluble ACE2 protein termed ACE2 618-DDC-ABD that has increased binding to SARS-CoV-2 and prolonged duration of action. Here we investigated the protective effect of this protein when administered intranasally to k18-hACE2 mice infected with the aggressive SARS-CoV-2 delta variant. k18-hACE2 mice were infected with the SARS-CoV-2 delta variant by inoculation of a lethal dose (2x104 PFU) and followed for up to 14 days. ACE2-618-DDC-ABD (10mg/kg) or PBS was administered intranasally six hours prior and 24 and 48 hours post viral inoculation. All animals in the PBS-control group had succumbed to the disease on day 7 post infection (0% survival) whereas, by contrast, there was only one casualty in the group that received ACE2-618-DDC-ABD (90% survival). Mice in the ACE2-618-DDC-ABD group had minimal disease as assessed by a clinical score and stable weight and both brain and lung viral titers were markedly reduced. These findings demonstrate the efficacy of a bioengineered soluble ACE2 decoy with extended duration of action in protecting against the aggressive delta SARS-CoV-2 variant. Together with previous work these findings demonstrate the universal protective potential against current and future emerging SARS-CoV-2 variants.

Introduction: On March 11, 2020, the World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) as a pandemic. The spread of the Delta variant of coronavirus started in June 2021 and accounted for the fifth peak of COVID-19 in Iran in July 2021. According to reports from other countries, vaccination protects against severe diseases caused by COVID-19, including the Delta variant. Studies have also shown that vaccination provides strong protection against SARS-CoV-2 infection, COVID-19-related hospitalization, and mortality. This retrospective cohort study was designed based on the medical care monitoring center (MCMC) database of Sayyad Shirazi Hospital.Methods: The following patient data were extracted for this study: demographic characteristics, signs and symptoms, ICU admission, need for aggressive oxygen therapy, including intubation, mortality, and vaccination status. Results: Being vaccinated was associated with a 4.14-fold increase in survival (adjusted OR=4.14; 95% CI: 2.22 to 7.69; P<0.01), and individuals in a younger age group demonstrated a 5.58-fold higher likelihood of surviving (adjusted OR=5.58; 95% CI: 4.25 to 8.14; P<0.01). The risk of severe COVID-19 was significantly lower in vaccinated individuals, showing a 3.12-fold decrease in risk (adjusted OR=3.12; 95% CI: 2.06 to 4.72; P<0.01), and in younger age groups, the risk exhibited a 3.28-fold decrease (adjusted OR=3.28; 95% CI: 2.66 to 4.04; P<0.01).Conclusion: The present results suggest that receiving at least one dose of COVID-19 vaccine had a significant relationship with decreased COVID-19 severity and mortality in vaccinated patients compared to unvaccinated patients.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe adverse event that was first observed during the global vaccination campaign against SARS-CoV-2 infection, specifically in those receiving adenoviral vector-based vaccines for Coronavirus disease 2019 (COVID-19). VITT develops 4 to 42 days post-vaccination and is characterized by the development of platelet-activating anti-platelet factor 4 (PF4) antibodies, leading to thrombocytopenia and thrombosis at unusual sites. The rise in awareness and subsequent prompt recognition of VITT was paramount in reducing mortality. Moreover, as vaccination campaigns around the world continue, a better understanding of VITT not only has important clinical implications but is also crucial for future vaccine development. In this review, we summarize the clinical features, pathophysiology, and incidence rates of VITT as well as highlight other anti-PF4 antibody-mediated disorders of growing clinical significance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, represents a serious threat to public health. The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry into host cells and is heavily glycosylated. In this study, we systemically analyzed the roles of 22 putative N-linked glycans in SARS-CoV-2 S protein expression, membrane fusion, viral entry, and stability. Using α-glycosidase inhibitors, castanospermine and NB-DNJ, we confirmed that disrupting the N-linked glycosylation process blocked the maturation of the S protein, leading to impairment of S protein-mediated membrane fusion. Single substitution of each of the 22 N-linked glycosylation sites with glutamine revealed that 9 out of the 22 N-linked glycosylation sites were critical for S protein folding and maturation, resulting in reduced S protein-mediated cell-cell fusion and viral entry. Of note, N1074Q mutation markedly affected S protein stability and induced significant receptor-independent syncytium (RIS) formation in HEK293T/hACE2-KO cells, and removal of the furin-cleavage site partially compensated instability of N1074Q mutation. Although the corresponding mutation in the SARS-CoV S protein (N1056Q) did not induce RIS in HEK293T cells, the mutants N669Q and N1080Q exhibited increased fusogenic activity and induced syncytia formation in HEK293T cells. Therefore, N-glycans on the SARS-CoV and SARS-CoV-2 S2 subunits are of great importance in maintaining the prefusion state of the S protein. The study revealed the critical roles of N-glycans in S protein maturation and stability, which have implications for the design of vaccines and anti-viral strategies.

The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

Viruses rely on host cells to replicate their genomes and assemble new viral particles. Thus, they have evolved intricate mechanisms to exploit host factors. Host cells, in turn, have developed strategies to inhibit viruses, resulting in a nuanced interplay of co-evolution between virus and host. This dynamic often involves competition for resources crucial for both host cell survival and virus replication. Iron and iron-containing cofactors, including iron-sulfur clusters, are known to be a heavily battled resource during bacterial infections where control over iron can tug the war in favor of the pathogen or the host. It is logical to assume that viruses also engage in this competition. Surprisingly, our knowledge about how viruses utilize iron (Fe) and iron-sulfur (FeS) clusters remains limited. The handful of reviews on this topic primarily emphasize the significance of iron in supporting the host immune response against viral infections. The aim of this review, however, is to organize our current understanding of how viral proteins utilize FeS clusters, to give perspectives on what questions to ask next and to propose important avenues for future investigations.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

This academic article examines the effectiveness of international humanitarian intervention in conflict zones. Humanitarian intervention refers to the use of military, diplomatic, or economic measures by external actors to protect civilians, promote human rights, and alleviate suffering in areas affected by armed conflict. The research employs a comprehensive approach, incorporating content analysis, case study, and historical analysis in its methodology. It explores the key challenges faced by international actors in implementing humanitarian interventions and evaluates their impact on conflict resolution and post-conflict reconstruction. Through this thorough analysis of case studies and scholarly literature, this article contributes to the ongoing debate surrounding the efficacy of international humanitarian intervention.

ICT and digital technology adoption, sustainable development, community empowerment and local wisdom and destinations uniqueness are keywords that will be further explored in the de-velopment of tourism villages in Kenderan as the most importance of tourism destinations de-velopment from the village level. Therefor this research is aimed at developing suitable model for post smart or wise tourism village through proposing Culture and Tradition Festival and the application of a circular economy. Circular economy development in tourism villages focuses on the application of sustainable production principles in the tourism value chain, namely in creating tourism experiences together with tourists (co-creation of experience) and integrated in a tourism system that supports environmental sustainability. This research is applied research conducted with a sequential mixed method research by conducting qualitative research through expert judgment and quantitative research by circulating questionnaire to tourists visiting Kenderan village, while the collected data is analyzed by Structural Equation Modelling to see the rela-tionship between variables. The results of this research show that creative event as the locality aspects of tourist village, digital competence, and sustainability practice are the building blocks of post smart tourism village, while digital competence and sustainable practice have significant mediating effect of locality on post smart tourism village. To make tourism village possesses sustainable competitive advantages, the village must explore and promote its locality aspects to differentiate its tourist village by identifying the valuable, rare, inimitable and non-substitutable tourism resources. The implication of this research is that to develop smart tourism destination wiser and distinctive, tourist village should explore their local values and resources, embed them into its tourism basic components and core resources, and co create, distribute, deliver and promote it to global market through technology adoption and global sustainability value.

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.

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.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of corona-virus disease 19 (COVID-19) and employs angiotensin-converting enzyme 2 (ACE2) as the recep-tor. Although the expression of ACE2 is crucial for cellular entry, we found that the interaction of ACE2 with the Spike (S) protein in the same cells led to its downregulation through degradation in the lysosomal compartment via the endocytic pathway. Interestingly, the ability of the S protein from previous variants of concern (VOCs) to downregulate ACE2 was variant-dependent and correlated with disease severity. The S protein from the Omicron variant, associated with milder disease, exhibited a lower capacity to downregulate ACE2 than that of the Delta variant, which is linked to a higher risk of hospitalization. Chimeric studies between the S proteins from the Delta and Omicron variants revealed that both the receptor-binding domain (RBD) and S2 subunit played crucial roles in the reduced ACE2 downregulation activity observed in the Omicron var-iant. In contrast, three mutations (L452R/P681R/D950N) located in the RBD, S1/S2 cleavage site, and HR1 domain were identified as essential for the higher ACE2 downregulation activity ob-served in the Delta variant than that in the other VOCs. Our results suggested that dysregulation of the renin-angiotensin system due to the ACE2 downregulation activity of the S protein of SARS-CoV-2 may play a key role in the pathogenesis of COVID-19.

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become a dominant strain. This phase 2 study aims to evaluate the immunogenicity of SCTV01E-2, a tetravalent protein vaccine, with a specific emphasis on its effectiveness against Omicron EG.5, comparing it with its progenitor vaccine, SCTV01E (NCT05933512). As of September 12, 2023, 429 participants aged ≥18 years were randomized to SCTV01E (N=215) or SCTV01E-2 (N=214) groups. Both vaccines showed increases in neutralizing antibody (nAb) against Omicron EG.5, with a 5.7-fold increase and a 9.0-fold increase in SCTV01E and SCTV01E-2 groups 14 days post-vaccination, respectively. The predetermined statistical endpoints were achieved, showing that the geometric mean titer (GMT) of nAb and the seroresponse rate (SRR) against Omicron EG.5 were significantly higher in the SCTV01E-2 group compared to SCTV01E. Additionally, SCTV01E and SCTV01E-2 induced a 5.5-fold and a 5.9-fold increase of nAb against XBB.1, respectively. Reactogenicity was generally mild and transient. No vaccine related SAEs, AESIs or deaths were reported. In summary, SCTV01E-2 elicited robust neutralizing responses against Omicron EG.5 and XBB.1 without safety concerns, underlining its potential as a versatile COVID-19 vaccine against SARS-CoV-2 variants.

The current globally dominant SARS-CoV-2 variants are showing immune escape and reduced susceptibility to antiviral drugs. Therefore, agencies responsible for drug evaluation and regula-tion such as the FDA and EMA are revising their emergency authorization use of several COVID-19 neutralizing antibodies. These NAbs proved to be unlikely effective against new variants espe-cially Omicron descendants and several pharmaceutical companies are pursuing the development of more potent neutralizing antibodies. To address the issue of using in silico prediction for the rapid assessment of anti-SARS-CoV-2 MAbs neutralization power, we used a computational method we developed previously, to evaluate 10 SARS-CoV-2 antibodies propensity to neutralize the new Omicron’s subvariants Eris (EG.5) and Pirola (BA.2.86) based on comparative binding affinity and previous experimental and clinical observations. Nine of these MAbs were once granted emergency use authorization, and one is currently under clinical investigation. The rapid, cost-effective in silico evaluation provided reliable predictions consistent with published clinical and experimental data. Furthermore, our data showed new potential therapeutic MAbs combi-nation that could be effective for the treatment countermeasure of the new Omicron’s subvariants Eris (EG.5) and Pirola (BA.2.86).

The host glycosylation mechanism synthesizes the carbohydrates of glycoproteins of viral envelopes. Due to the loss of the Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene by some mammalian species, including humans (negative-CMAH), Neu5Gc is no longer synthesized. Uptake of Neu5Gc by negative-CMAH species, through the intake of food products derived from positive-CMAH mammals, leads to incorporating Neu5Gc-glycans in the glycocalyx (xenosialylation). Neu5Gc, being a Mammalian-associated Carbohydrate Antigen (MCA), acts as a non-self-antigen, inducing an inflammatory reaction (Xenosialitis), and triggering the production of circulating antiNeu5Gc antibodies to attack/remove all incorporated Neu5Gc. In the state of Xenosialitis, the virus-neutralizing antibodies produced by a heavily xenosialylated patient following exposure to viral infection (including SarsCoV2) or anti SarsCoV2 vaccination cross-react against all incorporated non-self Neu5Gc-MCA glycans due to their resemblance with viral envelope antigens synthesized by the host glycosylation mechanism. In addition, the circulating anti-XeSias antibodies determine the massive removal of the circulating neutralizing FC-xeno-contaminated antibodies by the serum, living only the hyper-inflammatory agalattosylated antiviral IgG antibodies. Therefore, we hypothesize that the combination of antibody cross-reaction against non-self Neu5Gc-MCA glycans and the massive removal of the xeno-contaminated newly formed neutralizing antibodies in favor of hyper reactive antibodies, could be the cause of the massive inflammatory reaction (cytokine storm, coagulopathies, neuropathies) observed in Covid 19 patients or after anti-SarsCoV2 vaccination. This analysis is an invitation to investigate the post-infectious and/or post-vaccination adverse phenomena in the light of xenosialization as a key to understanding the severe post viral and post vaccine complications, including SARS-CoV2 infection or related vaccination.