The efficacy of an intranasal (IN) bovine respiratory syncytial virus (BRSV) administered in the face of passive immunity was assessed. Pooled colostrum was administered by intubation to fifty (50) beef-dairy crossbred calves the day they were born. The calves were transported to a research facility and were blocked by age and sex and randomly assigned into two groups, a sham-vaccinated intranasally with a placebo (sterile water) or vaccinated with a tri-valent modified live viral (MLV) vaccine. The calves were 92 days old when vaccinated (day 0). The calves were challenged by aerosolized BRSV on day 80 and day 81 as a respiratory challenge. The study was terminated on day 88. Lung lesion scores (LLS) were significantly lower for calves vaccinated with tri-valent MLV vaccine than those for calves that were sham-vaccinated. Serum neutralization (SN) antibody against BRSV in calves vaccinated with the tri-valent MLV vaccine demonstrated an anamnestic response on day 88. After challenge, the calves sham-vaccinated with the placebo lost weight while those vaccinated with the tri-valent MLV vaccine gained weight. In this study colostrum-derived antibodies did not interfere with the immune response or protection provided by one dose of the tri-valent MLV vaccine.

Microfiltration membranes derived from semi-crystalline polymers face various challenges when synthesized through the extrusion–casting technique, including the use of large quantities of polymer, long casting times, and the generation of substantial waste. This study focuses on synthesizing these membranes using spin-casting followed by stretch-induced pore formation. Recycled high-density polyethylene (HDPE) and virgin polyethylene powder, combined with a calcium carbonate filler, were used as the source materials for the membranes. The influence of the polymer-filler ratio with and without stretching on the morphology, tensile strength, and water flow rate was investigated. Optimal conditions were determined, emphasizing a balance between pore structure and mechanical integrity. The permeable membrane possessed a mean pore diameter of 500 nm, exhibited a tensile strength measuring 32 MPa, allowed water to flow at a rate of 19 ml/min, and had a water contact angle of 126°. These membranes effectively eliminated suspended particles from water, with their performance evaluated against that of commercially available membranes. This research outlines a synthesis route for microfiltration membranes tailored to semi-crystalline polymers and their plastic forms, utilizing the spin-casting technique.

Nystagmus induced by applying an intense vibratory stimulus to the skull (SVIN) indicates vestibular functional asymmetry. In unilateral vestibular loss, a 100-Hz bone-conducted vibration given to either mastoid immediately causes a primarily horizontal nystagmus. Test is performed in darkness to avoid visual fixation (VF) but there is no data about how much VF affects the often-intense SVIN. The aim is to analyze the amount of reduction of SVIN when VF is allowed during testing. Thus, all patients seen in a tertiary hospital for vertigo or dizziness with positive SVIN were included. SVIN was recorded for 10 seconds for each condition: without VF (aSVINwo) and VF (aSVINw). We obtained an aSVINwo and aSVINw as average slow-phase velocities (SPV) without and with VF. VF index (FISVIN) was calculated as the ratio of SPV. Among the 124 patients included, spontaneous nystagmus (SN) was found in 25% and the mSPV (without VF) of SN was 2.62.4º/s. Mean FISVIN was 0.270.29. FISVIN was 0 in 42 patients and >0 FISVIN <1 in 82 (mean FISVIN 0.390.02). Fixation suppression was found in all patients with SVIN in cases of peripheral vestibulopathy. FISVIN clearly delineates two populations of patients: with or without complete visual reduction of nystagmus.

The potential adverse effects of coronavirus disease 2019 (COVID-19) vaccinations raise public concerns. Data from Taiwan’s Vaccine Injury Compensation Program (VICP) can provide valuable insights. This study analyzed preliminary application data for COVID-19 vaccine compensation in Taiwan’s VICP, focusing on applicants receiving vaccines between March 2021 and June 2022. Among the 2941 adverse events, 113 cases (3.8%) were deemed causally associated with vaccination, 313 (10.6%) were indeterminate, and 2515 (85.5%) had no causal association. Nearly half (47.6%) of applicants were over 60 years old, and 76.6% had a history of preexisting chronic dis-eases. Among the 426 vaccine-associated or indeterminate cases, the most common causes were hematological diseases and thrombosis. There were 920 mortality cases reported, and 97.4% were unassociated with vaccination. Only five deaths were judged to be associated with the COVID-19 vaccination, all involving the adenovirus vector vaccine and thrombosis with thrombocytopenia syndrome. In conclusion, most compensation applications were not causally linked to vaccination. Compared to other countries, the number of applications in Taiwan’s VICP is relatively high. These findings may indicate a need to adjust the application requirements for compensation in Taiwan’s program.

Vaccine refusal and hesitancy pose a critical challenge to public health, leading to delays in vaccination and compromising herd immunity. To address this issue, we conducted a comprehensive observational study on the adult Spanish population in 2021. Through an online questionnaire, we explored the sociodemographic and sociocultural factors, beliefs, and opinions of those refusing or holding hesitancy about vaccines, and their vaccination behaviours by vaccine type and sex. Our findings revealed that vaccine refusal rates were relatively low (16.8%), and mainly associated with influenza vaccination (10.3%). Greater refusal of vaccination was observed in over 60 years old, in those expressing hesitancy due to vaccine components and opposing free and compulsory vaccination, unaware that vaccination protects the community and being against consuming cow’s milk and the use of infant formulas for breastfeeding. Vaccine hesitancy was greatest in individuals under 31 years old, women, parents of children under 15 years old, against compulsory vaccination, unaware that vaccination protects the community, with hesitancy due to vaccine costs, and in favour of alternative and complementary treatments. These insights underscore the need for strategies to improve education about vaccination and dispel misconceptions are crucial for effectively reducing vaccine refusal and hesitancy across the population.

Alzheimer’s disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the amyloid precursor protein (APP) gene. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.

The tumor necrosis factor receptor associated factor 1 (TRAF1) plays a key role in promoting lymphocyte survival, proliferation, and cytokine production. Recent evidence showed that TRAF1 plays opposing roles in monocytes and macrophages where it controls NF-B activation and limits pro-inflammatory cytokine production as well as inflammasome-dependent IL-1 secretion. Importantly, TRAF1 polymorphisms have been strongly linked to an increased risk of rheumatoid arthritis (RA). However, whether and how TRAF1 contributes to RA pathogenesis is not fully understood. Moreover, investigating the role of TRAF1 in driving RA pathogenesis is complicated by its multifaceted and opposing roles in various immune cells. In this study, we show that intraarticular injection of TRAF1 deficient macrophages into knee joints of wildtype (WT) mice subjected to the collagen antibody induced arthritis (CAIA) model of RA significantly exacerbated joint inflammation, immune cell infiltration and tissue damage compared to mice injected with WT macrophages. This study may lay the groundwork for novel therapies for RA that target TRAF1 in macrophages.

Background: Tachycardia-induced cardiomyopathy (TIC) is caused by prolonged tachycardia leading to left ventricular dilatation and systolic dysfunction with heart failure. Although TIC is more common in adult, it is rare in early infant. Methods: Clinical testing was performed as part of medical evaluation and management. Next gene se-quencing (NGS) was performed for a patient with TIC. Literature review about TIC was con-ducted. Results: The case was a 5-month-old infant referred the hospital due to symptoms with heart failure at least lasting two months. Heart rate was 200 beats per minute, left ventricular ejection fraction fell below 14%, and electrocardiograms showed atrial flutter, suggesting TIC. After cardiover-sion, there was no recurrence of atrial flutter, and cardiac function was improved at 98 days after tachycardia arrest. There were no pathogenic variants identified according to NGS. Literature review identified 8 early infantile cases with TIC reported. However, there were no previous re-ports such as our case with longer duration of TIC. Conclusions: Improvement of cardiac function depends on the duration of TIC. TIC should be considered in all patients with a dilated cardiomyopathy of uncertain origin and who have tachycardias such as atrial flutter.

Influenza viruses pose a continuing public health challenge due to their high mutation rate and the need for annual vaccine updates. A recent advancement in nanoparticle-based vaccine technology for developing a universal influenza vaccine. We focused on four key studies investigating the use of lipid nanoparticles (LNPs), nanoparticle immunogens, and multivalent epitope-based nanoparticles. The studies demonstrated promising results. The single-dose mRNA -LNP vaccine targeting five influenza B virus antigens effectively protected mice from a broad range of strain. Additionally, nanoparticle immunogens designed to display multiple influenza virus strains induced broad protective immunity in mice. Furthermore, LNPs enhanced the efficacy of mRNA and protein subunit vaccines by stimulating robust T follicular helper cell and humoral responses. Finally, an intranasal multivalent epitope-based nanoparticle vaccine offered broad protection against diverse influenza viruses. These findings highlight the potential of nanoparticle-based approaches for developing a universal influenza vaccine that offers long-lasting and broad-spectrum protection. Further research is needed to evaluate the safety and efficacy of these novel vaccines in humans.

The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to free HPV vaccine is a public health concern. HPV is one of the most common Sexually Transmitted Infections (STIs) in Nigeria with high-risk HPV-16 and 18 genotypes. In this study, we explored the predictors of self-reported HPV infections and HPV genital warts infection among a population of students, non-academic staff, and academic staff of Ibrahim Badamasi Babangida (IBB) university located in Lapai, Nigeria. We also assessed their knowledge about HPV infections and genotypes, and sexual behaviors. An online cross-sectional study was conducted by setting up a structured questionnaire on google form and it was distributed to the University community via Facebook and other social media platforms of the university. The form captured questions on HPV infection, knowledge about HPV infection and genotypes, as well as sexual health of the participants. All variables were described using frequencies and percentage distribution, chi-squared test statistics was used to explore the association between HPV infection (medical records of HPV infection) and the participants’ profile, and logistic regression analysis was performed to examine the factors associated with HPV genital warts infection among the population. This study reveals those participants between the ages of 26 – 40 years (81.3%) and those currently not in a union (26.4%) who have self-reported having HPV-16 and -18 genotypes. Also, participants between 26 – 40 years of age (OR: 0.45, 95%CI: 0.22 – 0.89) reported to be carriers of HPV genital warts. Therefore, this study reveals the factors associated with HPV infection and genital warts peculiar to IBB university students and staff. Hence, we suggest the need for HPV awareness programs and free HPV vaccine availability at IBB university.

Varicella (chickenpox) is one of the most common infectious diseases in preschool children and can be prevented by immunization. While immunization program promotes higher vaccine coverage, there are still challenges with implementing vaccination programs particularly in low-income countries. Economic barriers can increase inequality in vaccination, which highlights the importance of distributing cost-effective varicella vaccines. Varicella vaccines have been developed with two main Varicella-Zoster Virus (VZV) strains globally: MAV/06 and Oka strains. Most of the vaccines are based on the Oka strain, while MAV/06 strain vaccines were exclusively developed by GC Biopharma. Although more than 30 million doses of MAV/06 vaccines as cost-effective vaccines have been distributed internationally, there is no comprehensive review on safety, immunogenicity, and effectiveness of MAV/06 vaccines in the literature. This paper aims to summarize and present more than 30 years of accumulated evidence from research on safety, immunogenicity, and effectiveness of MAV/06 vaccines. We expect that MAV/06 vaccines as cost-effective varicella vaccines make a significant contribution to improving global public health and health equality in children.

This study aims to demonstrate the possibility of incorporating a natural antioxidant biomolecule, into polymeric porous scaffolds. To this end, Poly-L-Lactic Acid (PLLA) scaffolds were produced using the Thermally Induced Phase Separation (TIPS) technique and additivated with different amounts of Rosmarinic Acid (RA). The scaffolds, with a diameter of 4 mm and a thickness of 2 mm, were characterized with a multi-analytical approach. Specifically, Scanning Electron Mi-croscopy analyses demonstrated the presence of an interconnected porous network, character-ized by a layer of RA at the level of the pore’s surfaces. Moreover, the presence of RA biomole-cules increased the hydrophilic nature of the sample, as evidenced by the decrease in contact angle with water from 128° to 76°. This approach is cost-effective, and it could be customized with different biomolecules, offering the possibility of producing porous polymeric structures con-taining antioxidant molecules. These scaffolds meet the requirements of tissue engineering and could be offered a potential solution to reduce inflammation associated with scaffold implantation thus improving tissue regeneration.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies using various types of stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity of unlimited proliferation and differentiation to cardiomyocytes, are a promising cell source for myocardial regeneration therapy. This review discusses the current status of cardiac regenerative therapy using iPSCs.

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients who have a thrombophilic predisposition. In this case, a female patient with no family history of thrombophilia who had pediatric antiphospholipid syndrome (APS) developed deep vein thrombosis (DVT) when she was 6 years old; 6 months after receiving a second dose of the BNT162b2 vaccine, DVT reoccurred. The original thrombi were found in the right common iliac vein and the inferior vena cava, with concomitant left pulmonary infarction. The patient was treated with anticoagulants for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine exacerbated the patient’s APS by activating coagulation, causing thrombosis recurrence. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development.

This study aimed to evaluate a cantilever beam-type piezoelectric energy harvester operating on train-induced vibrations for powering Wireless Sensor Networks (WSNs) used in railway track monitoring systems. The harvester's behaviors under different conditions are simulated in MATLAB using the analytical model. Natural frequency, maximum deflection, and stress were calculated with greater precision using eigenfrequency and stationary analysis using COMSOL Multiphysics. At a base excitation of 2 g and a resonant frequency of 4.38 Hz, the simulated results showed that the developed energy harvester prototype could generate up to 14 V of AC output voltage and 550 mW of output power. These findings highlight the promising potential of the proposed energy harvester for transforming train mechanical energy into electrical power. This energy harvester's viability and dependability for real-world applications in monitoring railway tracks are supported by developed analytical and simulation models.

We estimated the risk of blood clots after COVID-19 vaccination accounting for the roles of vaccination in reducing the infection rate, and indirectly lowering the risk of blood clots caused by infection. A self-controlled case series method was used to examine the association between blood clots and COVID-19 vaccination. To deal with the bias due to under-reported infection among non-hospitalized subjects, a case-control study was used to compare the risk of blood clots in infected subjects to control subjects who were hospitalized due to physical injury. We found increased risks of blood clots after vaccination (incidence rate ratio is 1.13, 95% confidence interval (CI): [1.03, 1.24] after the first dose and 1.23, 95% CI: [1.13,1.34] after the second dose). Furthermore, vaccination attenuated the increased risk of blood clots associated with infection (odds ratio (OR) = 2.16, 95% CI: [1.93, 2.42] in unvaccinated versus OR=1.46, 95% CI: [1.25, 1.70] in vaccinated). A causal model was used to explain and weigh up possible risk factors for blood clots after COVID-19 vaccination. After accounting for vaccine efficacy against infection and the protection against infection-associated blood clots, receiving the COVID-19 vaccines decreases the risk of blood clots, especially during high infection rate period.

Globally, habitat fragmentation has increased the proximity between wildlife, humans, and emerging predators such as free-ranging dogs. In these fragmented landscapes, encounters between primates and dogs are escalating, with primates often falling victim to dog attacks while navigating patchy landscapes and fragmented forests. We aim to investigate how these primates deal with the simultaneous threats posed by humans and predators, specifically focusing on the adaptive strategies of Central Himalayan Langur (CHL) in the landscape of fear. To address this, we conducted a behavioral study on the CHL in an agro-forest landscape, studying them for a total of 3912 hours over two consecutive years. Our results indicate that, compared to their most common resting behavior, CHL allocate more time to feeding and locomotion, and less time to socializing in the presence of humans and predatory dogs. Additionally, they exhibit increased feeding and locomotion and reduced social behavior in agro-forest or open habitats. These behavioral patterns reflect adaptive responses to the landscape of fear, where the presence of predators significantly influences their behavior and resource utilization. This study suggests measures to promote coexistence between humans and wildlife through the integration of effective management strategies that incorporate both ecological and social dimensions of human-wildlife interactions.

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden as well, if the absolute risk of infection during child-bearing age increases. Dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with low current burden and high transmission intensity. Low or declining rubella virus transmission intensity is concurrently associated with both greater disease burden and greater vaccine effectiveness. The risk of increasing burden through vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase and a large, immediate burden decrease strongly favors RCV introduction.

Crystallization of glass through conventional thermal annealing in a furnace is a well-understood process. However, crystallization by femtosecond (fs) laser brings another dimension to this process. The pulsed nature of the irradiation necessitates a reevaluation of parameters for optimal crystallization and to understand the particularities in the case of using fs laser. This includes adjusting the laser pulse energy, the repetition rate, and the writing speed to either initiate nucleation or achieve substantial crystal growth. Therefore, a key challenge to this work is to establish reliable calculations for understanding the relation of the size of the crystallized region with respect to an ongoing transition (e.g., solid-to-solid, liquid-to-solid), and accounting for the aforementioned laser parameters. In this context and based on previous work, we simulate a temperature distribution (in space and time) to model the thermal treatment at any point in the glass. By setting the condition that the temperatures are between the glass transition and melting temperature, we can deduce the crystallized region size to be compared with experimental observations. For that purpose, the knowledge of the beam width at the focal point and of the absorbed beam energy fraction are critical inputs that were extracted from experiments found in the literature. After that, management of the crystallization process and the width of the crystallization line can be achieved according to pulse energy e.g. crystallite size, and also the effect of the scanning speed can be understood. Among the main conclusions to highlight, we disclose the laser conditions that determine the extent of the crystallized area and deduce that it is never interesting to increase the pulse energy too much but rather the repetition rate for uniform crystallized line.

Three autonomous communities have been the ones that, in the 2022-2023 season, anticipated the document approved by the Public Health Commission, recommending influenza vaccination for all children aged 6 to 59 months. The main objective of this work is to evaluate the attitude of healthcare professionals towards the first universal vaccination campaign in our region, as well as the acceptability of the vaccines used and the attitude towards the piloting of school vaccination. Cross-sectional, survey-based, descriptive study. All healthcare professionals involved in the campaign were invited to participate. The 91.9% of surveyed professionals thought that flu vaccination from 6 to 59 months was important or very important. 89.8% had previous experience regarding the intramuscular vaccine. The professionals valued the intranasal vaccine significantly more positively; however, there were no differences when asking for each of the vaccines without comparison. The inhaled vaccine was preferred by 97.5% for the following campaign. Piloted school vaccination showed 75% acceptance. The inhaled vaccine was preferred by most professionals and the piloted school vaccination was highly accepted, and independently associated to the importance of vaccination as considered by physicians, being a medical doctor, and participation in the pilot program.

Earthquake-triggered landslides are one of the most significant hazards worldwide. These landslides, involving small or large volumes, can develop in debris flow or avalanche with high mobility and long-runout distance. The motion processes of this kind of landslide also quite complicated. This study reproduced the motion processes of two landslides using the LS-RAPID program. The Aso Bridge landslide occurred on April 16, 2016, with rapid and long-runout distance characteristics. The Kataragai landslide occurred on April 9, 2018, travelling with flow-like behavior. Through field investigations and laboratory experiments, features and mechanical parameters of these two landslides were obtained. In the LS-RAPID program, the pre-failure models and motion processes of these two landslides were established and reproduced. Results indicated that sliding speed and travelling morphology at different intervals were considered as two indicators to describe their motion process. However, while sliding speed of these two landslides have significant differences with sliding speeds of actual landslides, the final morphologies after failure were consistent with those observed in the field investigation.

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s^-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modelling informed by biology can provide new pathphysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.

Objectives: To study the differences between malignant hypermetabolic axillary lymphadenopathy (MHL) and COVID-19 vaccine-associated axillary hypermetabolic lymphadenopathy (VAHL) using clinical imaging. Methods: A total of 1,096 patients underwent Positron Emission Tomography-Computed Tomography (PET-CT) between June 1, 2021 and April 30, 2022, at Ehime University Hospital. In total, 188 patients with axillary lymphadenopathy after the COVID-19 vaccination were evaluated. The patients were classified into three groups such as VAHL (n=27), MHL (n=21), and equivocal hypermetabolic axillary lymphadenopathy (EqHL; n=140). Differences in lymph nodes (LNs) swellings were statistically analyzed using clinical imagings (echography, CT, and 18F-FDG PET) statistically. Results: MHL included a higher female population (90.5%) owing to a higher frequency of breast cancer frequency (80.9%). Axillary LNs of MHL did not show any LN fatty hilums (0%); however, those of VAHL and EqHL did (15.8 and 36%, respectively). After the logistic regression analysis of the patients who had axillary lymphadenopathy without any LN fatty hilums, the minor axis length and ellipticity (minor axis/major axis) in the largest axillary LN, SUVmax, and Tissue-to-Background Ratio (TBR) were useful in distinguishing malignant lymphadenopathies. Receiver-operating characteristic (ROC) analysis indicated that a cut-off value of ≥7.3 mm for the axillary LN minor axis (sensitivity: 0.714, specificity: 0.684) and of ≥0.671 for ellipticity (0.667 and 0.773, respectively) in the largest LN with the highest SUVmax and TBR were predictive of MHL. Conclusion: Axillary lymphadenopathy ≥7.3 mm of the minor axis and ≥0.671 of ellipticity in LN without fatty hilum suggests malignancy even in patients who have received COVID-19 vaccination. Further examinations such as 18F-FDG PET are recommended for such patients

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

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

We report neutralization titer data against contemporary SARS-CoV-2 sublineages from an ongoing, open-label, phase 2/3 trial of a single 30-μg dose of monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine. Healthy participants had previously received ≥3 doses of a US-authorized mRNA vaccine, with the most recent being a bivalent Omicron BA.4/BA.5-adapted vaccine administered ≥150 days before study vaccination. In this analysis, Omicron XBB.1.5, BA.2.86, and JN.1 serum neutralizing titers were assessed at baseline and 1 month after vaccination in a subset of ≥18-year-olds (N = 40) with evidence of previous SARS-CoV-2 infection. Immunogenicity was also evaluated in a demographically matched group of participants who received bivalent BA.4/BA.5-adapted BNT162b2 in another study (ClinicalTrials.gov Identifier: NCT05472038). The XBB.1.5-adapted BNT162b2 vaccine elicited higher XBB.1.5, BA.2.86, and JN.1 neutralizing titers than those elicited by bivalent BA.4/BA.5-adapted BNT162b2. Overall geometric mean fold rises in neutralizing titers from baseline to 1 month after vaccination were higher among participants who received XBB.1.5-adapted BNT162b2 than those who received bivalent BA.4/BA.5-adapted BNT162b2 for XBB.1.5 (7.6 vs 5.6), slightly higher for JN.1 (3.9 vs 3.5), and similar for BA.2.86 (4.8 vs 4.9). ClinicalTrials.gov Identifier: NCT05997290.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods utilised often for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This Review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups, so they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission, has many potential benefits. These include reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review.

Understanding vaccine hesitancy in organ transplant recipients (OTR) is critical, given clear, alt-hough attenuated, benefits from vaccination. Adult OTR were surveyed regarding vaccine-related values and a novel outcome variable called Vaccine Acceptance Composite Score (VACS) was built as the average Likert score of 7 domains of vaccination confidence. Of 46 OTR included (93.5% kidney transplant recipients), 32.6% were female, 13.3% Black, 6.77% Hispan-ic/Latino/a/x; median age was 58 years. Patients were most concerned about COVID-19 vac-cine-associated risks (46.3%), its potential effect on allograft (47.6%) and motives of government officials involved with vaccine policy (55.6%). Politically conservative patients were likely to have a significantly lower VACS, while those who lived with someone ≥65 had a higher VACS. The VACS was not significantly associated with race, income, religious beliefs, comorbidities, COVID-19 history, or influenza vaccination status. Higher VACS was significantly associated with ≥3 and ≥4 COVID-19 immunizations. This study highlighted political beliefs and elderly household members as correlates of vaccine acceptance among OTR. The VACS may be a useful tool to help standardize multifaceted analyses in vaccination-focused behavioral research, as well as identify individuals and groups at risk for vaccine hesitancy, who may benefit from tai-lored outreach and educational interventions.

The severe and complex COVID-19 symptoms, often needing hospital care, occur suddenly, late in the virus replication stage of SARS-CoV-2 infection. Hospitalised patients have tissue damage due to micro-clots at multiple sites. Could long-covid, also clinically variable, be a milder form caused by “nano-clots”, too small to cause detectable tissue damage? The timing and suddenness of the onset of serious disease needs an explanation. A paper reported on the first 20 children needing urgent hospital care. No child had any symptoms prior to suddenly becoming seriously ill, only one had a positive PCR test but all had positive SARS-CoV-2 antibody test. That finding indicated to me that this onset occurred at the moment of sero-conversion. An emerging viral moiety, the virion-IgG-antibody complex, has concentrations rapidly increasing, then decreasing. It is known that influenza-IgG-antibody-complex consists of many virions bound together by the antibody. It seems a reasonable step to propose that SARS-2, being a large virus and having many spike proteins, can form larger clumps of virus-IgG-antibody complexes than with influenza, the former being sufficiently large to initiate micro-clots. Therefore, my hypotheses is that the SARS-CoV-2 virion-antibody complex initiates micro-clot formation. Either before or after sero-conversion, the complex will be at too low a concentration to initiate micro-clots. To be useful, a hypothesis should be testable, provide explanations and give predictions. My presentation will give examples. I like the way that several apparently separate pieces of a jig-saw puzzle have come together to form a single picture. [I suggest that the reader scrolls down to the addenda [10,11 & 12] before reading the ICAR Poster]

WHO reported an estimated 249 million malaria cases and 608,000 malaria deaths in 85 countries in 2022. A total of 94% of malaria deaths occurred in Africa, 80 % of which were children under 5. In other words, one child dies every minute from malaria. The RTS,S/AS01 malaria vaccine, that uses the Plasmodium falciparum circumsporozoite protein (CSP) to target sporozoite infection of the liver, achieved modest efficacy. The Malaria Vaccine Implementation Program (MVIP), coordinated by the WHO and completed at the end of 2023, found that immunization reduced mortality by only 13%. To further reduce malaria death, development of a more effective malaria vaccine is a high priority. Three major malaria vaccine targets being considered are the level of sporozoite liver infection, merozoite red blood cell (RBC) infection, and mosquito midgut infection. These targets involve specific ligand-receptor interactions. However, current malaria vaccine candidates that target two major parasite population bottlenecks, liver infection and mosquito midgut infection, do not focus on such parasite ligands. Here we evaluate the potential of newly identified parasite ligands as novel malaria vaccine antigens.

Background: Respiratory syncytial virus[ RSV] is a lethal overwhelming defectiveness that influences people all over the world. The infection gets down in the lower respiratory tract and does not disperse to the remainder of the body. The objective of the study: Bioinformatics was used to create an mRNA vaccine against the Respiratory syncytial virus( RSV). Methodology: Lipid nanoparticle vaccines containing the Respiratory syncytial virus's surface fusion protein's mRNA were created for the current screening experimental investigation. Lipid nanoparticles[ LNP] with a particle size of around 90 nanometres that were created using the hot micro-emulsion process comprise the current vaccine delivery system. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current immunization lacks antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies worsen infection by enhancing viral entrance and replication in the host cells, activating cytokines and the complement cascade through the production of immunological complexes, or both. However, the current LPN-RSV mRNA vaccine of the surface fusion protein resulted in the formation of potent neutralizing antibodies with persistent protection, especially for newborns and elderly individuals who get the ideal dose regimen. Conclusion: The invention of the LNP-mRNA RSV vaccine, which might prevent RSV-caused bronchiolitis and fatal pneumonia, made the current study promising

Understanding gene expression changes in chicks after vaccination against Newcastle Disease (ND) can reveal vaccine biomarkers. There is limited data on chicks’ early immune response after ND vaccination. Two trials aimed into this knowledge gap. In experiment one, forty-two 13 days-old specific pathogen free (SPF) chicks were used. Harderian glands (Hg) and tracheas (Tc) from five birds per group were sampled at 12, 24, and 48 hours post-vaccination (hpv) to evaluate the gene transcription levels by RNA sequencing (RNA-seq) and RT-qPCR. Results of RNA-seq were compared by glmFTest, while results of RT-qPCR were compared by t-test. With RNA-seq, significant up-regulation of interferon related genes along with JAK-STAT signaling pathways regulation was observed in the Hg at 24- hpv. None of the DEGs identified by RNA-seq were positive for RT-qPCR. Experiment 2 used one-hundred and twelve SPF and commercial chickens at 1 day-old and 14 days-old. Only the commercial birds had maternal antibodies for NDV. By RNA-seq, twenty core DEGs associated with innate immunity and viral genome replication inhibition were identified. Genes previously unlinked to NDV response, such as USP41, were identified. This research present genes with potential as immunity biomarkers for vaccines, yet further investigation is needed to correlate the core gene expression with viral shedding post-vaccination.

The emergence of the H3N2 influenza virus in 1968 marked a significant event as it crossed the species barrier. Since then, ongoing mutational dynamics have led to the formation of antigenic clusters, prompting the World Health Organization to advocate for regular updates to H3N2 vaccines. Research in the Western Pacific region underscores the necessity for heightened awareness and effective control strategies. Stemming from avian influenza A, the 1968 H3N2 influenza pandemic resulted in the deaths of one million people globally, with its seasonal variants primarily affecting older individuals and causing severe illness due to antigenic drift. To address the challenge of vaccine efficacy against H3N2 mutations, researchers are exploring innovative strategies such as precise antigenic material administration, controlled release patterns, understanding immune system mechanisms, and glycan engineering. This review comprehensively examines various aspects of the Influenza A (H3N2) virus, encompassing its virological characteristics, evolutionary trends, global epidemiology, vaccination strategies, antiviral interventions, and emerging diagnostic approaches. It underscores the impact of antigenic variation on vaccine design and effectiveness, seasonal outbreak patterns, pandemic potential, and the interplay between viral factors and host immune responses. Moreover, the review evaluates antiviral therapies and the issue of drug resistance, emphasising the necessity for multidisciplinary approaches involving researchers, healthcare professionals, and policymakers to comprehend H3N2 and enhance public health interventions.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

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

Abstract: Canine ehrlichiosis is a zoonotic disease transmitted by ticks, posing a formidable challenge to both veterinary and public health sectors worldwide. Across continents and regions, the prevalence rates of Ehrlichia canis exhibit significant variation, underlining the necessity for a nuanced and globally informed approach to understanding and combating this disease. The review navigates through this complexity, shedding light on the intricate pathogenesis of the illness. Central to this understanding is the bacterium's adept manipulation of the host's immune response, contributing to the diverse clinical manifestations observed in infected animals. Diagnostic methodologies, crucial for timely intervention and management, are subjected to critical assessment. From traditional microscopy to modern molecular techniques and serology, each approach is scrutinized for its strengths and limitations. By acknowledging these nuances, the review aims to equip practitioners with the knowledge necessary to make informed diagnostic decisions. A central tenet of this review is the advocacy for an integrated "One Health" approach. By leveraging advancements in genomics, proteomics, and artificial intelligence, there is a potential to enhance diagnostic accuracy and develop innovative therapeutic and preventive strategies globally. This collaborative approach recognizes the interconnectedness of human, animal, and environmental health, offering a holistic framework for tackling complex zoonotic diseases like canine ehrlichiosis. In conclusion, this review serves as a beacon of knowledge, illuminating the multifaceted landscape of canine ehrlichiosis. Through its synthesis of scientific literature and emphasis on methodological rigor, it provides a foundation upon which future research and interventions can be built. With a unified commitment to "One Health" principles and the integration of cutting-edge technologies, there exists the potential to mitigate the impact of this disease and safeguard both animal and human well-being worldwide

COVID-19 pandemic disproportionately affected seven South Asian countries because of rampaging virus and weak health system response. Vaccination commenced in all countries during early 2021, once the vaccines became available in the international market. Vaccines were donated by international development partners, friendly countries and procured utilizing domestic resources and financial support from various agencies. All countries opted for a phasing of the vaccination by prioritizing high risk populations which included health care personnel, front line workers and elderly with comorbidities. Seven vaccines that had WHO emergency authorization usage were utilized in South Asia. India produced more than 2.4 billion doses of AstraZeneca vaccine and has indigenously developed five COVID-19 vaccines. Vaccine inequity was obvious and characterized by fewer people in South Asia vaccinated with single dose vis a vis the developed countries. Vaccine hesitancy was another obstacle that kept the vaccination rates low. Difficult to reach areas in Afghanistan, Bhutan, Maldives, Nepal could not fully access vaccines. South Asian countries need to strengthen their health system for efficient deployment of vaccines in future health emergencies. At the same time the global agencies and developed countries must address the issue of vaccine access to low-income countries to mitigate the impact of pandemic all over the world.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

Abstract: Thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge for their delivery wherever needed. Freeze-drying of viral vectored vaccines is a prom-ising approach but remains challenging due to the water removal process from the outer and in-ner parts of the virus. In the case of enveloped viruses, freeze-drying induces increased stresses on the envelope, which often leads to inactivation of the virus. In this study, we design a method to freeze-dry a recombinant Vesicular Stomatitis Virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. Since the envelope of VSV is composed of 50% lipid and 50% protein, the formula-tion study focused on both the protein and lipid portions of the vector. Formulations were pre-pared primarily using sucrose, trehalose, and sorbitol as cryoprotectants; mannitol as a lyopro-tectant; and histidine as a buffer. Initially, the infectivity of rVSV-SARS-CoV-2 and cake stability were investigated at different final moisture contents. High recovery of the infectious viral titer ( 0.5 to 1 log loss) was found at 3-6% moisture content with no deterioration of the freeze-dried cakes. To further minimize infectious viral titer loss, the composition and concentration of the ex-cipients were studied. An increase from 5 to 10% of both cryoprotectants and lyoprotectant, to-gether with the addition of 0.5% gelatin, resulted in the improved recovery of infectious virus titer and stable cake formation. Moreover, the secondary drying temperature of the freeze-drying pro-cess showed a significant impact on the infectivity of rVSV-SARS-CoV-2. The infectivity of the vector declined drastically when the temperature was raised above 20°C. Throughout a long-term stability study, formulations containing 10% sugar (sucrose/trehalose), 10% mannitol, 0.5% gelatin, and 10 mM of histidine showed satisfactory stability for six months at 2-8°C. The development of this freeze-drying process and the optimized formulation minimizes the need for a costly cold chain distribution system.

Background: RSV, or respiratory syncytial virus, is a deadly condition that is present all over the world today. The infection is initially contained in the lower respiratory tract without systemic transmission. The objective of the study: Bioinformatics was used in Egypt to create an mRNA vaccine against the Respiratory syncytial virus (RSV). Methodology: In the present screening experimental study, a lipid nanoparticles vaccine of mRNA of the surface fusion protein of Respiratory syncytial virus was manufactured. The present vaccine delivery system was lipid nanoparticles with a particle size of approximately 90 nanometres, manufactured by the hot micro-emulsion method. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current vaccination lacked antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies exacerbate infection by activating cytokines and complement cascade through the formation of immune complexes or enhancement of the virus entry and replication in the host cells. On the other hand, the current RSV mRNA vaccine of the surface fusion protein consequent on the production of powerful neutralizing antibodies with prolonged immunity especially to infants and elderly candidates who received the optimal dosage regimen.

The last 50 years witnessed the emergence of various so called “hyperpolarization technologies” that allow generating large magnetizations of spin ensembles. This Editorial Essay provides a brief overview of the use of these technologies in various fields, including medicine, chemistry, and quantum sensing. It is concluded that critical questions still need to be addressed to harness benefits of nuclear hyperpolarization in clinical medical imaging while interdisciplinary innovation can unlock potential of novel (yet unexplored) methods. My hope is that this Editorial Essay provides valuable insights into the current state and future directions of spin technologies.

Drugs are known to cause substantial liver injury, with hepatotoxicity ranging from asymptomatic increase of liver enzymes to hepatic failure. HIV/AIDS patients, with compromised immune systems, are especially vulnerable to opportunistic infections such as tuberculosis (TB). Patients with co-infection frequently get combined antiretroviral (ART) and antitubercular (ATD) regimens, which can cause hepatotoxicity. Hepatotoxicity has been linked to commonly administered antiretroviral drug regimens as well as first-line antitubercular agents such isoniazid, rifampin, and pyrazinamide, which are required for the treatment of both drug-sensitive and drug-resistant tuberculosis. As a result, there is an urgent need to investigate treatments based from traditional herbs known for their hepatoprotective abilities against ART and ATD-induced liver injury. Many researchers have investigated the effectiveness of medicinal plants in treating chemically caused hepatotoxicity. Medicinal plants are high in phytochemicals and secondary metabolites, both of which have a variety of medicinal benefits. Currently, there is a lack of specific therapeutic regimens to address this adverse effect, and management often relies on symptomatic treatment or therapy withdrawal. Traditional medicinal plants may have the potential to restore normal liver function, enzyme activity, and cellular structure in response to ART and ATD-induced hepatotoxicity. This review aims to examine the scientific evidence supporting the use of medicinal plants as hepatoprotective agents against liver damage induced by ART and ATDs.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

The theory of heavy ion double charge exchange (DCE) reactions proceeding by effective rank–2 isotensor interactions is presented. Virtual pion–nucleon charge exchange interactions are investigated as the source for induced isotensor interactions, giving rise to the Majorana DCE (MDCE) reaction mechanism. MDCE is of a generic character, proceeding through pairs of complementary (π±,π∓) reactions in the projectile and target nucleus. The dynamics of the elementary processes is discussed where the excitation of pion–nucleon resonances are of central importance. Investigations of initial and final state ion–ion interactions show that these effects are acting as vertex renormalizations. In closure approximation, well justified by the finite pion mass, the second order transition matrix elements reduce to pion potentials and effective two–body isotensor DCE interactions, giving rise also to two–body correlations in either of the participating nuclei. Connections to neutrinoless Majorana double beta decay (MDBD) are elucidated at various levels of dynamics, from the underlying fundamental electro–weak and QCD scales to the physical scales of nuclear MDBD and MDCE physics. It is pointed out that heavy ion MDCE reactions may also proceed by competing electro–weak charge exchange processes, leading to lepton MDCE by electrons, positrons, and neutrinos.

Introduction the outbreak of the Israel-Gaza conflict, initiated by a major attack on the civilian population in Israel provided a tragic opportunity to study the community wide association between severe emotional stressors related to acts of war and the incidence and clinical characteristics of Takotsubo cardiomyopathy (TCM) in this scenario. Methods Eight consecutive cases of TCM diagnosed during the first 50 days of the Israel-Gaza conflict were retrospectively collected from two southern medical centers who provided care to most of the war victims throughout the period of monitoring. The medical records were thoroughly reviewed and analyzed. Results During the monitoring period, the incidence of TCM increased substantially compared to the control period. Eight patients were included in the analysis. All patients were female and 100% of patients presented within the first 3 weeks of conflict whereas after this initial phase, despite the continuing war, the incidence of TCM reverted to pre-conflict levels. Two patients (25%) were under 50 years of age. All patients had hazardous clinical characteristics including severe left ventricular (LV) dysfunction (≤35%) and prolonged QTc interval (>500 ms). Five patients (62.5%) experienced complications. Nevertheless, no in-hospital mortality was reported. Conclusions Repeated exposure to severe emotional stress, on both personal and national level, due to mass crisis such as war is associated with an increased incidence of TCM potentially with high-risk phenotype in comparison to TCM following other, less potent, psychological insults.

The chemotactic cytokine fractalkine (FKN, chemokine CX3CL1) has unique properties resulting from the combination of chemoattractants and adhesion molecules. The soluble form (sFKN) has chemotactic properties and potently attracts T cells and monocytes. The membrane-bound form (mFKN) facilitates diapedesis and is responsible for cell-to-cell adhesion, especially by promoting the strong adhesion of leukocytes (monocytes) to activated endothelial cells with the subsequent formation of an extracellular matrix and angiogenesis. FKN signaling occurs via CX3CR1, which is the only known member of the CX3C chemokine receptor subfamily. Signaling within the FKN-CX3CR1 axis plays an important role in many processes related to inflammation and the immune response, which often occur simultaneously and overlap. FKN is strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokine secretion, and it may act locally as a key angiogenic factor in the highly hypoxic tumor microenvironment. The importance of the FKN/CX3CR1 signaling pathway in tumorigenesis and cancer metastasis results from its influence on cell adhesion, apoptosis and cell migration. This review presents the role of the FKN signaling pathway in the context of angiogenesis in inflammation and cancer. The mechanisms determining the pro- or anti-tumor effects are presented, which are the cause of the seemingly contradictory results that create confusion regarding the therapeutic goals.

Abstract: Lipidic carriers employed for the entrapment, encapsulation and precise targeting the bioactive compounds offer significant advantages to the biomedical, pharmaceutical, nutraceutical and cosmeceutical industries. These lipid and phospholipid-based vesicles can improve the solubility, permeation, pharmacokinetics, pharmacodynamics and bioavailability of the encapsulated material. As a matter of fact, nano-sized phospholipid vesicles have attained the highest success rate in commercialization among the available drug encapsulation technologies. Nevertheless, developing industrially acceptable products still remains a challenge. Among the main disadvantages of conventional lipidic carriers are their instability in the biological environments, and their sensitivity to changes in the pH, temperature and enzymes. To overcome these problems, the new generation of phospho/lipid-based carrier systems was developed using ingredients from microorganisms living in extremely harsh environments (i.e., archeaeobacteria). The present entry aims to review unique features of archaeolipids and recent developments in their application for the encapsulation of genetic material as well as their role and function as adjuvants and vaccine candidates.

Gardasil 4, a human papilloma virus vaccine, has been shown to protect against various cancers, including cervical cancer. Common side effects include injection site pain, fever, headaches, and muscle aches. In some individuals, the severe side effect of postural orthostatic tachycardia syndrome (POTS) has been reported. POTS is characterized by the abnormal response of lightheadedness, blurry vision, and dizziness while transitioning to an upright posture. POTS predominately affects women, with more than eighty-five (85) percent of POTS patients being female. POTS on average, takes five years and eleven months to receive the diagnosis. Additionally, ​A strong association between POTS and Ehlers Danlos Syndrome Type III (EDS) exists. Eighty (80) percent of patients with EDS have POTS. This severe side effect dictates that providers need to be aware of this strong association of HPV vaccinations and POTS. ​In this report we will present a case of a young women with a past medical history significant for EDS type III who was diagnosed with POTS after receiving Gardasil 4 vaccination. This case demonstrates the need for physicians to be aware of the association of POTS with EDS type III and HPV vaccination. Physician awareness of the associations, signs and symptoms of POTS and earlier testing at the first presentation of signs and symptoms will limit the negative impact on patient’s quality of life.

Parental refusal of childhood vaccines is a growing public health concern. Numerous reasons exist for this refusal, including religious, personal, and philosophical beliefs, and safety concerns. However, parental refusal of childhood vaccines is not simply an individualized problem for the family; this impacts herd immunity and affects the entire community. To improve vaccination rates among the pediatric population, understanding the thought process and decision-making behind parental opposition and refusal of vaccinations is essential. Using a survey developed to assess attitudes towards recommended childhood vaccines and the COVID-19 vaccine, this study examined the correlation between vaccine literacy and hesitancy among parents and legal guardians of elementary school-aged children in the Midwest. Responses were analyzed using Chi-squared tests on “R” software. Significant negative correlations were found between COVID-19 hesitancy and vaccine literacy, and resistance towards all vaccines and vaccine literacy. No significant negative correlations were found between hesitancy towards all vaccines and vaccine literacy, or hesitancy and literacy among different income and education brackets. Our results suggest that vaccine education may lessen vaccine hesitancy among parents and may be an essential factor in improving vaccination rates among the pediatric population.

Vaccines decrease morbidity and mortality. Nevertheless, their benefits depend on public response. During COVID-19, vaccine hesitancy and refusal were rampant, threatening public health. A thorough understand-ing of opponents' arguments is required to address the diffusion of unreliable information on social media and prevent vaccine hesitancy from developing into vaccine refusal. Accordingly, the article examines vac-cine opponents' justifications on social media. Textual content analysis of reader comments on three health-related Israeli Facebook pages was conducted. Data collection encompassed the Israeli COVID-19 vaccination period from October 2020 to May 2022. The comments were analyzed according to the health beliefs model (HBM). We found that vaccine opponents were characterized by low perceptions of the severity of the disease combined with high perceptions of the damages of the vaccine; low perceived benefits of vac-cine compliance; vaccine hesitancy and fear along with public distrust as barriers to change; and call for ac-tion to resist the vaccine and spread related anti-establishment views on the web. As vaccination hesitancy was found to develop into public distrust in the state systems and escalate into conspiracy beliefs and an-ti-vaccination activism, its early detection may prevent future vaccine resistance.

To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in the phosphate and composition of the renal filtrate, and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully this will raise questions and stimulate new ideas for further research.

The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

Hepatitis C virus (HCV) is a major medical health burden and leading cause of chronic liver disease and cancer worldwide. More than 58 million people are chronically infected with HCV, with 1.5 million new infections occurring each year. An effective HCV vaccine is a major public health and medical need as recognized by the World Health Organization. However, due to the high variability of the virus and its ability to escape the immune response, HCV rapidly accumulates mutations making a vaccine a formidable challenge. An effective vaccine must elicit broadly neutralizing antibodies (bnAbs) in a consistent fashion. After decades of studies from basic research through clinical development, the antigen of choice is considered to be the E1E2 envelope glycoprotein due to conserved, broadly neutralizing antigenic domains located in the constituent subunits of E1, E2, and the E1E2 heterodimeric complex itself. The challenge has been elicitation of robust humoral and cellular responses leading to broad virus neutralization due to the relatively low immunogenicity of this antigen. In view of this challenge, structure-based vaccine design approaches to stabilize key antigenic domains have been hampered due to the lack of E1E2 atomic-level resolution structures to guide them. Another challenge has been development of a delivery platform in which a multivalent form of the antigen can be presented in order to elicit a more robust anti-HCV immune response. Recent nanoparticle vaccines are gaining prominence in the field due to their ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both the cellular and humoral components of the immune system. This review focuses on recent advances in understanding the E1E2 heterodimeric structure to facilitate a rational design approach and the potential for development of a multivalent nanoparticle-based HCV E1E2 vaccine. Both aspects are considered important in the development of an effective HCV vaccine that can effectively address viral diversity and escape.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as a potential therapeutic strategy. The potential role of the mannose-modified lipid calcium phosphate nanoparticle vaccine in enhancing the anti-tumor immune response was investigated. The aim of this study was to investigate the effect of mannose modification on the immune response of nanoparticles in regulating the tumor microenvironment through systematic review and analysis and to explore its potential clinical application in tumor therapy. Currently, despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and overexpression of immunosuppressive factors limit its clinical application. Therefore, this study will explore how to intervene in the immunosuppressive mechanism in the tumor microenvironment through mannose-modified lipid calcium phosphate nanoparticle vaccines so as to improve the immunotherapy effect of tumor patients and provide new ideas and strategies for the field of tumor therapy.

Luminescent carbon dots (CDs) were locally synthesized in the core of CYTOP fibers using IR femtosecond laser direct writing (FLDW), a one-step simple method serving as a post-treatment of the genuine fiber. This approach enables the creation of several types of modifications such as ellipsoid voids. The CDs and photoluminescence (PL) distribute at the periphery of the voids. The PL spectral properties were studied through Excitation Emission Matrix in the visible range and excitation/emission spectrum in UV/visible range. Our finding reveals the presence of at least 3 distinct luminescent species, facilitating a broad excitation range extending from UV to green, and light emission spanning from blue to red. The average laser power and dose influence the quantity and ratio of these luminescent CD species. Additionally, we measured the spatially resolved lifetime of the luminescence during and after the irradiation. We found longer lifetimes at the periphery of the laser-induced modified regions and shorter ones closer to the center, with a dominant lifetime ~ 2ns. Notably, unlike many other luminophores, these laser-induced CDs are insensitive to oxygen, enhancing their potential for display or data storage applications.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A&gt;G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

Human Immunodeficiency Virus (HIV) infection and its latent recurrent infection make vaccine development a significant challenge for traditional vaccines; however, the mRNA delivery of multiepitope antigens capable of creating antibodies against the surface proteins of HIV-1 and HIV-2 along with their respective Nef proteins, responsible for the latent infection can bring a most effective, as well as affordable solution to the unresolved epidemics of HIV. In this paper, we present the complete design of a multiepitope vaccine to prevent acute infections and inactivate Nef proteins that block the MHC-1 and MHC-2 pathways to hide the virus for later reinfection.

The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have abnormally hard outer shell (low M disorder; i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far was found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2 especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 amd later in Omicron, is associated with attenuation according to the Shell-Disorder-Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.

Despite the importance of influenza vaccination for healthcare workers (HCWs), their uptake remains challenging. This study aimed to measure influenza vaccine hesitancy among HCWs in Nakhon Phanom province, Thailand. A representative cross-sectional survey was conducted at six hospitals during August – September 2020 using a self-administered questionnaire. HCWs delaying getting influenza vaccines, accepting but unsure, or refusing with doubts were categorized as hesitant. Those accepting without any doubts were classified as non-hesitant. Vaccine hesitancy determinants were identified by multivariable logistic regression analysis. A total of 338 participants (97%) completed the questionnaires; most were female nurses working at district hospitals without pre-existing chronic medical conditions. Nearly 60% of participants (197/338) exhibited influenza vaccine hesitancy, and significant factors included age above 50 years adjusted odds ratio [aOR] 3.2, 95% CI 1.3-8.5), fair knowledge of influenza/vaccination (aOR 0.4, 95% CI 0.2-0.8), and negative influence of other HCW (High level– aOR 2.3, 95% CI 1.1-4.8; Moderate level- aOR 2.1, 95% CI 1.1-4.4). Imparting updated information to the HCW combined with positive guidance from influential peers may help reduce this hesitancy.

The coronavirus pandemic was declared by the World Health Organization (WHO) in 2020, and a global genetic vaccination program has been rapidly implemented as a fundamental solution. However, many countries around the world have reported that so-called genetic vaccines, such as those using modified mRNA encoding the spike protein and lipid nanoparticles as the drug delivery system, have resulted in post-vaccination thrombosis and subsequent cardiovascular damage, as well as a wide variety of diseases involving all organs and systems, including the nervous system. In this article, based on these circumstances and the volume of evidence that has recently come to light, we call the attention of medical professionals to the various risks associated with blood transfusions using blood products derived from people who have suffered from long COVID and from genetic vaccine recipients, including those who have received mRNA vaccines, and we make proposals regarding specific tests, testing methods, and regulations to deal with these risks. We expect that this proposal will serve as a basis for discussion on how to address post-vaccination syndrome and its consequences following these genetic vaccination programs.

Infectivity assays are the key analytical technology for development of manufacturing processes for virus-based therapeutics. Here, we introduce a novel assay format that utilizes label-free bright field images to determine the kinetics of infection-dependent changes in cell morphology. In particular, cell rounding is directly proportional to the amount of infectious virus applied, enabling rapid determination of viral titers in relation to a standard curve. Our kinetic infectious virus titer (KIT) assay is stability-indicating and, due to its sensitive readout method, provides results within 24 hours post-infection. Compared to traditional infectivity assays, which depend on a single readout of an infection endpoint, cumulated analysis of kinetic data by a fit model results in precise results (CV &lt; 20%) based on only three wells per sample. This approach allows for a high throughput with ~400 samples processed by a single operator per week. We demonstrate the applicability of the KIT assay for VSV-GP and NDV, but it can potentially be extended to a wide range of viruses that induce morphological changes upon infection. The versatility of this assay, combined with its independence from specific instruments or software, makes it a promising solution to overcome the analytical bottleneck in infectivity assays within the pharmaceutical industry and as a routine method in academic research.

Stallion mules have been used as working equids in several countries. Aggressiveness, under the influence of testosterone, resulted in the necessity for surgical castration before work training. The gonadotropin-releasing hormone (GnRH) vaccine may be an alternative method for immunocastration in mules. The objectives were to evaluate the effect of GnRH vaccine on anti-GnRH antibody production, serum testosterone level, clinical adverse effects, and behavior toward human manipulation. Twenty-five mules were separated into 3 groups: Control-intact, Control-castrated, and Treatment. Treatment was further divided into subgroups according to condition (intact or unilateral cryptorchid) and age. Treatment received 195 µg GnRH vaccine intramuscularly at week 0, 4, and 8. Anti-GnRH antibody increased at week 6 and 10, then gradually decreased to baseline at week 22. Treatment-intact-young had the highest anti-GnRH antibody, resulting in lower serum testosterone levels during week 2-6 and 12-16 compared to Control-intact. Subcutaneous edema adjacent to the injection site was detected only in Treatment-intact after booster vaccination. During week 6-22, the behavioral scores of Treatment significantly changed toward at ease with human contact compared to a score before vaccination. In conclusion, mules responded to GnRH vaccine, which could temporarily suppress testosterone for up to 16 weeks.

Inflammation is a cause of number of disorders. Many anti-inflammatory drugs are available to cure and prevent inflammation and its related disorders. Some of the drugs are from plant and animal origin. Among animals snake venom is also utilized as treatment option of certain disorders. In the current study the venom of N. oxiana from Northern areas of Pakistan is assayed to determine its anti-inflammatory activity. The Naja oxiana is also called central Asian cobra is endemic to Central Asia. Naja oxiana belong to family Elapidae and it is highly venomous snake. The venom has many enzymatic proteins as well as nonenzymatic proteins that is neurotoxins. The venom is lethal having very high mortality rate and the death may occur due to respiratory failure in 45 minutes to 24 hrs depending upon the nature and amount of venom. As the venom is highly toxic so initially after venom milking its protein estimation was done and toxicity profile and LD50 was determined to find out its therapeutic dose at which anti-inflammatory activity was observed. The toxicity and anti-inflammatory activity was determined on mice model. Inflammation was induced by carrageenan induced peritonitis method. The inflammatory markers ROS, TNF-α and IL-β were determined by ELIZA in peritoneal fluid. The LD50 of crude venom, fraction 1 and fraction 2 was found as 34 µg/kg, 7.4 µg/kg and 416 µg/kg respectively. Anti-inflammatory activity crude venom, fraction 1 and fraction 2 was found at dose 19 µg/kg, 1.8 µg/kg and 267 µg/kg respectively. The levels of inflammatory markers reduced after therapeutic dose administration of venom and its fractions that indicates that it can be utilized as anti-inflammatory agent and so can be effective in various disorders.

In this study, we define screening maps for Italy that classify sites based on their potential for triggering landslides. To this end, we analyze seismic hazard maps and hazard disaggregation results on a national scale considering four spectral periods (0.01s, 0.2s, 0.5s, and 1.0s) and three return periods (475, 975, and 2475 years). First, joint distributions of magnitude (M) and distance (R) from hazard disaggregation are analyzed by means of an innovative approach based on image processing techniques to find all modal scenarios contributing to the hazard. In order to obtain the M-R scenarios controlling the triggering of earthquake-induced landslides at any computation node, mean and modal M-R pairs are compared to empirical curves defining the M-R bounds associated with landslide triggering. Three types of landslides are considered (i.e., disrupted slides and falls, coherent slides, and lateral spreads and flows). As a result, screening maps for all of Italy showing the potential for triggering landslides based on the level of seismic hazard are obtained. The maps and the related data are freely accessible at the following web address: https://distav.unige.it/rsni/slideq.php.

The intricate mechanisms of the immune response elicited by vaccines and the interplay between the immune system and the central nervous system (CNS) are poorly understood. This review explores these mechanisms, emphasizing the interplay between the immune system and the central nervous system (CNS). A critical aspect is the examination of how vaccine-induced immune responses can interact with the CNS, influencing neuroinflammation and neuroimmune interactions. Furthermore, the link between vaccination and persistent symptoms observed in long-COVID patients is discussed. Vaccination initiates a complex cascade of events, starting with the production of specific proteins, such as S1/S2 spike proteins, leading to robust immune activation in the axillary lymph nodes. The role of macrophages and antigen-presenting cells (APCs) in cytokine production, antigen presentation, and the stimulation of B and T cells highlights the sophistication of the adaptive immune response. The migration of immune cell-derived exosomes to the brain plays a dynamic role in CNS inflammation, neurodegenerative processes and long COVID. On the other hand, the prolonged presence of viral and vaccine-derived spike proteins may contribute to the complex pathophysiology of Long-COVID, shedding light on the delicate balance between beneficial immune responses and possible adverse neurological outcomes of vaccination. It is worth rigorous monitoring and further research to understand the mechanisms of neuroinflammation and the persistence of spike proteins and their long-term effects on the brain, emphasising the importance of a nuanced approach to vaccine safety and efficacy in the context of COVID-19 and beyond.Principio del formulario

Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune response against ASFV. Studies, espe-cially in sensible host species, focused on unravelling protective mechanisms will contribute to the development of safer and more effective vaccines. The present study provides a detailed analysis of phenotypic and functional data on cellular responses induced by intradermal immunization and subsequent boosting of domestic pigs with the naturally attenuated field strain Lv17/WB/Rie1, as well as the mechanisms underlying protection against intramuscular challenge with the virulent genotype II Armenia/07 strain. The transient mild to moderate increase of IL-8 and IL-10 in serum observed after immunization might be directly correlated with survival. Protection was also associated with a robust ASFV-specific polyfunctional memory T cell response, where CD4CD8 and CD8 T cells were identified as the main cellular sources of virus-specific IFNγ and TNFα. In parallel to cytokine response, these T-cell subsets also showed specific cytotoxic activity as evidenced by the increased expression of the CD107a degranulation marker. Along with virus-specific multifunctional CD4CD8 and CD8 T responses, the increased levels of antigen experienced cytotoxic CD4 T cells observed after challenge in immunized pigs might also contribute to control virulent infection by killing mechanisms targeting infected antigen-presenting cells. Future studies should elucidate whether the memory T-cell responses evidenced in the present study persist and provide long-term protection against further ASFV infections.

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

Cameroon introduced the malaria vaccine in its routine immunization programme on 22 January 2024, in the 42 districts out of 200, among the most at risk of malaria. A cross-sectional analysis of data on vaccine key events in the introduction roadmap and vaccine uptake during the first 30 days was conducted. In addition to available gray literature related to the introduction of the malaria vaccine, data on malaria vaccine uptake by vaccination session, collected through a digital platform, were analyzed. A total of 1,893 reports were received from 22 January 2024 to 21 February 2024 from 766 health facilities (85% of overall completeness). Two regions out of 10 recorded less than 80% of completeness. As of 21 February 2024, 13,811 children have received the first dose of the malaria vaccine, including 7,124 girls (51.6%) and 6,687 boys (48.4%). Thirty six percent of children were vaccinated through outreach sessions versus 61.5% through sessions in fixed posts. The overall monthly immunization coverage with the first dose was 37%. Early results have shown positive attitudes towards and acceptance of malaria vaccines. Suboptimal completeness of data reporting and low coverage highlight persistent gaps and challenges in vaccine rollout.

Mycobacterium tuberculosis was responsible for 1.3 million deaths worldwide in 2022. Bacillus Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB); however, it has limited protective efficacy in adults. In this study, we constructed a recombinant vaccinia virus expressing Ag85B from M. tuberculosis using a novel attenuated vaccinia virus (KVAC103). We then analyzed the immunogenicity of prime-boost inoculation strategies using recombinant KVAC103 expressing Ag85B (rKVAC85B) compared to BCG. In both the rKVAC85B prime-boost and the BCG prime-rKVAC85B boost inoculation regimens, rKVAC85B induced the generation of specific IgG and the secretion of IFN-γ by immune cells. In vitro analysis of Mycobacterium growth inhibition revealed a comparable immune-mediated pattern of outcomes. Furthermore, bacterial loads in the lungs were significantly lower in mice inoculated with the BCG prime-rKVAC85B boost, than in the BCG-only group following a rechallenge infection with both H37Rv and HN878 strains of M. tuberculosis. These findings collectively suggest that KVAC103, incorporated into a viral vector, is a promising candidate for a novel TB vaccine platform that is effective against multiple TB strains, including H37Rv and HN878, and that rKVAC85B effectively stimulates immune responses against TB infection.

COVID-19 vaccine hesitancy and its enablers would shape community uptake of non-covid vaccines such as oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera endemic region of the Democratic Republic of Congo. We conducted a community-based survey in Bukavu. The survey included characteristics, intention to take OCV and COVID-19, reasons for COVID-19 hesitancy, and thinking and feeling about COVID-19 vaccines. Poisson regression analyses were performed. Of the 1708 respondents, 84.66% and 77.57% were hesitant to OCV alone and to both OCV and COVID-19, respectively. Hesitancy to COVID-19 vaccines rose OCV hesitancy by 12% (crude Prevalence Ratio, [cPR]=1.12, 95%CI[1.03-1.21]). Independent predictors of OCV hesitancy were living in semi-urban area (adjusted Prevalence Ratio [aPR]=1.10, 95%CI[1.03-1.12]), religious refusal of vaccines (aPR=1.06, 95%CI[1.02-1.12]), concerns about vaccine safety (aPR=1.05, 95%CI[1.01-1.11]) and adverse effects (aPR=1.06, 95%CI[1.01-1.12]), as well as poor knowledge (aPR=1.07, 95%CI[1.01-1.14]). Conversely, the belief about COVID-19 vaccine effectiveness reduced OCV hesitancy (aPR=0.76, 95%CI[0.62-0.93]). COVID-19 vaccine hesitancy and its drivers exhibiting a significant domino effect on OCV uptake. Addressing vaccine hesitancy through community-based health literacy interventions would likely improve the introduction of novel non-COVID-19 vaccines in post-COVID-19 era.

This paper presents a comprehensive analysis of the SEIRS COVID-19 pandemic model with saturated incidence rate. By modifying the existing model and proposing a new simplified version, we investigate the dynamics of disease transmission, including the impact of saturation terms on disease spread. Through stability analysis at disease-free and endemic equilibria, we aim to enhance understanding of the spread of COVID-19 and inform effective control strategies. Drawing on mathematical models and epidemiological insights, this study contributes to the ongoing efforts to combat the global pandemic.

The development of effective vaccines against SARS-CoV-2 remains a critical challenge amidst the ongoing global pandemic. This study introduces a novel approach to enhance mRNA vaccine efficacy by leveraging the untranslated region (UTR) of TMSB10, a gene identified for its significant mRNA abundance in antigen-presenting cells. Utilizing the GEO database, we identified TMSB10 among nine genes with the highest mRNA abundance in dendritic cell subtypes. Subsequent experiments revealed that TMSB10's UTR significantly enhances the expression of a reporter gene in both antigen-presenting and 293T cells, surpassing other candidates and a previously optimized natural UTR. Comparative analysis demonstrated that TMSB10 UTR not only facilitated higher reporter gene expression in vitro but also showed marked superiority in vivo, leading to enhanced specific humoral and cellular immune responses against the SARS-CoV-2 Delta variant RBD antigen. Specifically, vaccines incorporating TMSB10 UTR induced significantly higher levels of specific IgG antibodies and promoted a robust T-cell immune response, characterized by increased secretion of IFN-γ and IL-4 and the proliferation of CD4+ and CD8+ T cells. These findings underscore the potential of TMSB10 UTR as a strategic component in mRNA vaccine design, offering a promising avenue to bolster vaccine-induced immunity against SARS-CoV-2 and potentially other pathogens.

The aim of the present work is to explore a different non-traditional approach to higher dimensional spacetime which differs from the usual approaches such as large extra space dimensions, warped extra space dimensions and multiple extra time dimensions. This approach will be referred to as "Dynamic" higher dimensional spacetime. By this term will be introduced a new kind of higher dimensional spacetime (more than the usual 3+1 dimensions), which behaves dynamically in the sense that time is not a fixed dimension but is the extra plus one dimension to the spatial dimensions of the phenomenon we are studying. For a higher dimensional phenomenon, the lower dimensional time will behave as space and the new time will be a plus one dimension, meaning if we study a 3-dimensional phenomenon then time is the usual 4th dimension but if we are studying a 4-dimensional phenomenon then its time will be an extra 5th dimension and for this phenomenon the 4th dimension will behave as space. All spatial dimensions are indistinguishable from each other and behave in the exact same way, which means that the important parameter is not the dimension we are studying (for example the 4th or the 5th) but the number of dimensions in which a phenomenon can interact and how higher dimensional phenomena interact with lower ones. This non-traditional approach to higher dimensional spacetime may appear confusing at first but will become clearer in the rest of the paper. For this reason, we will first associate the time dimension with propagation relative to space dimensions and change orthogonal to them in order to give the reader a better intuition. Following that, we will describe how higher - dimensional phenomena would appear to us, the 3 - dimensional observer and try to set some guidelines on how we should mathematically model higher - dimensional phenomena in order for us to make accurate predictions of their behaviour. Then we will express the general framework of a "Dynamic" higher - dimensional spacetime and turn our gaze to 4+1 – dimensional phenomena. We will explore how a mass term arises for 4 – dimensional waves by generalizing the frequency – speed – wavelength relation of 3D waves and give a basic description on a possible way to describe a 4+1 – dimensional disturbance in a scalar Energy Field in order to make accurate predictions on our 3+1 dimensional plane. In this framework we will derive the Klein – Gordon equation by generalizing the wave equation and ignoring all lower than 4+1 - dimensional disturbances and compere our mass term findings with the Klein – Gordon equation mass term and with results from gravity – induced quantum interference experiments. Lastly, we will describe how a "Dynamic" 5 - dimensional spacetime would appear in a 3D observer and examine whether our findings are compatible with quantum mechanics and the special theory of relativity.

Among the many Lysosomal Storage Disorders (LSDs) that would benefit from the establish-ment of novel cell models, either patient-derived or genetically engineered, is Mucopolysaccha-ridosis type II (MPS II). In fact, even though a specific therapeutic approach does exist for this disorder (Enzyme Replacement Therapy, ERT, with recombinant human IDS) and haematopoiet-ic stem cell transplantation (HSCT) may also hold promise whenever the disorder is diagnosed soon enough, both approaches have their own drawbacks. Here we present our results on the establishment and characterization of two MPS II pa-tient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population is isolated from LSD patient samples obtained from the oral cavity. Taking into account our results on the molecular and biochemical characterization of those cells and our first insights on their subcellular MPS phenotype, we consider these cells will be a valuable tool for both pathophysiological assessments and drugs screenings. Ultimately, we believe patient-derived dental pulp stem cells (DPSC) may represent a feasible alternative to induced pluripotent stem cells (iPSC) in many labs with standard cell culture con-ditions and limited (human and economic) resources.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

Alzheimer's disease (AD) remains a significant challenge in the field of neurodegenerative disor-ders, even nearly a century after its discovery, due to the elusive nature of its causes. The develop-ment of drugs that target multiple aspects of the disease has emerged as a promising strategy to address the complexities of AD and related conditions. The immune system's role, particularly in AD, has gained considerable interest, with nanobodies representing a new frontier in biomedical research. Advances in targeting antibodies against amyloid-β (Aβ) and using messenger RNA for genetic translation have revolutionized the production of antibodies and drug development, open-ing new possibilities for treatment. Despite these advancements, conventional treatments for AD, such as Cognex, Exelon, Razadyne, and Aricept, often have limited long-term effectiveness, under-scoring the need for innovative solutions. This necessity has led to the incorporating of advanced technologies like artificial intelligence and machine learning into the drug discovery process for neurodegenerative diseases. These technologies help identify therapeutic targets and optimize lead compounds, offering a more effective approach to addressing the challenges of AD and similar conditions.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

The statistical analysis of impact of the top 50 solar flares of X-class (1997-2023) on the global seismic activity, as well as on the earthquake preparation zones located in illuminated part of the globe and in the area of 5000 km radius around the subsolar point was carried out. It is shown by a method of epoch superposition that for all cases the increase of seismicity is observed, especially in the region around the subsolar point (up to 38%) during 10 days after the solar flare in comparison with preceding 10 days. The case study of aftershock sequence of strong M=9.1 earthquake (Su-matra-Andaman Islands, 26.12.2004) after the solar flare of X7.2 class (20.01.2005) demonstrated that the number of aftershocks with magnitude M≥2.5 increases more than 20 times after the solar flare with a delay of 7 days. For the case of the Darfield earthquake (M=7.1, 04.09.2010, New Zealand) it was shown that strong solar flares of class X and M probably triggered two strong aftershocks (M>6) with the same delay of 6 days on the Port Hills fault, which is the most sensitive to external electromagnetic impact from point of view of the fault electrical conductivity and orientation. Based on the obtained results the possible application of natural electromagnetic triggering of earthquakes is discussed for a short-term earthquake prediction using confidently recorded strong external electromagnetic triggering impacts on the specific earthquake preparation zones, as well as ionospheric perturbations due to aerosol emission from the earthquake sources recorded by satellites.

Secondary movement disorders (SMDs) represent a heterogeneous group of neurological conditions characterized by abnormal, involuntary movements resulting from various underlying causes. This comprehensive review aims to thoroughly understand SMDs, including their epidemiology, pathophysiology, clinical manifestations, diagnostic approach, and management strategies. SMDs encompass a spectrum of movement abnormalities, including dystonia, chorea, athetosis, myoclonus, tics, and tremors. They can arise from a multitude of etiologies, such as drug-induced effects, post-infectious processes, metabolic disturbances, and structural brain lesions. The epidemiology of SMDs varies depending on the underlying cause, with some conditions being more prevalent in specific populations or age groups. Understanding the pathophysiology of SMDs is crucial for accurate diagnosis and targeted management. Diagnosing SMDs requires a comprehensive approach, including a detailed history, physical examination, laboratory investigations, neuroimaging studies, and sometimes electrophysiological studies. Management of SMDs is multifaceted and may involve pharmacological, non-pharmacological, and surgical interventions. Individualized treatment plans are essential, considering the underlying cause, severity of symptoms, and patient preferences. Emerging concepts in the field of SMDs include advancements in genetic research, identification of biomarkers, and development of novel therapeutic approaches. There is a growing focus on patient-centered care and improving the quality of life for individuals with SMDs. In conclusion, SMDs pose diagnostic and therapeutic challenges, requiring a multidisciplinary approach for optimal management. Continued research and collaboration are essential for advancing our understanding and treatment of these complex disorders.

Aquaculture is rapidly becoming one of the pivotal sectors in the farm economy, driven by the increasing demand for high-quality animal protein at an affordable cost, especially with the escalating human population. However, the expansion of high-density fish populations also brings forth a challenge – the rapid transmission and spread of infectious disease agents among them. To combat this, vaccination is emerging as a reliable and standardized method for providing immunity against viral and bacterial outbreaks. The ideal vaccine is expected to be safe, effective, economical, and easily administered. The fish vaccination industry continually publishes new information on fish immunology and vaccinology, contributing to the improvement of vaccine formulation and efficacy. This review aims to offer insights into the current status of bacterial, viral, and parasitic diseases, discuss existing vaccinations, and address potential industry-threatening diseases like infectious edwardsiellosis, motile aeromonas septicemia, TiLV, salmon anemia, vibriosis, and white spot disease. Technological advancements have played a crucial role in enhancing our understanding of fish immunological mechanisms, leading to improved vaccine administration and the development of recombinant live attenuated, subunit, DNA, and RNA vaccines. However, challenges such as oral tolerance, vaccine degradation, and stressful environments persist, impacting vaccine efficacy. Addressing these challenges and gaining a deeper understanding of the fish immune system and host-pathogen interactions will be pivotal for future improvements, contributing to the sustainability of aquaculture and enhancing global food security.

In contemporary construction, the prevalence of vibration serviceability issues in lightweight and slender structures has become increasingly common, owing to advancements in building materials and construction methods. While these structures often meet the criteria for ultimate limit states, they can still elicit complaints due to excessive vibrations induced by human activity. To address this challenge, the Integral Resonant Control (IRC) technique has emerged as a favored approach for actively damping vibrations in various systems. This study introduces a fresh perspective on implementing a multi-input multi-output (MIMO) IRC scheme for active vibration control (AVC) specifically tailored for pedestrian structures utilizing inertial mass actuators. Building upon a common framework and design methodology outlined in previous research, this work presents a novel application of MIMO IRC for AVC. The designed controller is rigorously tested and implemented on a laboratory floor structure to validate its efficacy.

Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobinuria, chronic cold agglutinin disease, immune thrombocytopenia, haemophagocytosis, hemophagocytic lymphohistiocytosis, and many other blood related conditions. The observation of adverse events has motivated investigation into the cardiovascular mechanisms of harm by Covid-19 vaccines, and the biodistribution of vaccine contents. Biodistribution may not be limited to the body of the vaccine recipient, as a growing body of evidence demonstrates the possibility of secondary exposure to vaccine particles. These can be via bodily fluids and include the following routes of exposure: blood transfusion, organ transplantation, breastfeeding, and possibly other means. As covid-19 vaccines are associated with an increased risk of stroke, the persistence of vaccine artifacts in the blood presents a possible threat to a recipient of a blood donation from a vaccinated donor who suffered from vaccine induced thrombosis or thrombocytopenia. (VITT) We assess the feasibility and significance of these risks through an overview of the case report literature of blood disorders in vaccinated individuals, pharmacovigilance reports from the US Vaccine Adverse Events Reporting System (VAERS) and a meta-analysis of the available literature on organ transplants from vaccinated organ donors. Our analysis establishes biological mechanistic plausibility, a coherent safety signal in pharmacovigilance databases for secondary vaccine contents exposure (for the cases of blood transfusion and breastfeeding) and also an elevated level of adverse events in organ transplants from VITT-deceased donors, echoing increases in organ transplantation related complications seen in national statistics for some countries. Secondary exposure to vaccine artifacts is a potential explanation for some of the cases put forth, and requires a deeper investigation.

This research follows the publication of recent scoping and systematic reviews of existing literature on vaccine literacy (VL), its relationship to vaccine hesitancy (VH), and associated variables, such as vaccination beliefs, attitudes, and behaviors towards immunization. In this review, 17 articles were selected, published between December 2022 and November 2023, in which VL tools were used, most of which support the notion of a negative association between VL and VH, although not confirmed by others. Moreover, the definitions of the variables under consideration were not homogeneous between studies, some aimed to evaluate the association of VL with vaccine confidence, while others were more focused on outcomes such as willingness to be vaccinated or vaccine uptake. The complexity of the factors underlying VL, and the heterogeneity of the methods applied in the studies, in particular the limitations of cross-sectional surveys, still make it difficult to have a comprehensive understanding of the role of VL. Therefore, it is important to develop future assessment tools that consider not just the measurement of psychological factors connected to the motivational aspect of VL, but also those related to knowledge and competencies. For this purpose, a theoretical framework is proposed, where the positioning of VL at the intersection between antecedents and beliefs/attitudes leading to behaviors explains why and how VL serves as a tool and a critical, direct, or mediating driver of vaccination choices, overcoming VH and increasing vaccination rates, operating at personal, as well as at organizational and community level.

Rabbit hemorrhagic disease virus disease 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly between infected individuals. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Within the spectra of lanthanide atoms quite often overlapping spectral lines (blends) are observed. On the example of complicated blend situations within Pr I and La I it is shown that in such cases a combination of optogalvanic and laser-induced fluorescence detection is necessary to find all transitions contributing to the observed spectral signature.

The wealth of data obtained during the past 20 years using Laser-Induced Breakdown Spectroscopy (LIBS) indicates that the technique is very promising to detect small chemical contents of alloying elements. The potential of LIBS was looked more seriously during the past two decades or so as more data were obtained on Aluminum and steel to study the phenomena in the condition of local thermodynamic equilibrium and time-delay between a Q-switch laser and an intensified CCD camera. Since the past decade, some data on compounds were also shown to be useful in determining small concentrations of harmful elements. This manuscript is intended to show that the technique of LIBS performance is very promising in fields such as micro-machining, in alloying element analysis, surface cleaning and environmental applications even with lightweight spectrometers having a relatively low resolution, which can potentially be air-borne.

Hiccups can significantly reduce the quality of life of patients and can occur as a drug side effect. Previous report using the Drug Adverse Event Database revealed sex-specific differences in the incidence of drug-induced hiccups. However, the pathogenesis of drug-induced hiccups remains unknown, and there is limited evidence on its treatment or prevention. This study examined molecular initiating events (MIEs), which are the starting point of adverse events, to investigate the drug-induced pathways of hiccups. We extracted drugs suspected to cause hiccups using FDA Adverse Event Reporting System, a large database on adverse drug reactions. Information on drugs suspected to be associated with hiccups were extracted from the overall population and sex-specific subgroups divided. In each data table, the predicted activity values of nuclear receptors (NRs) and stress response pathways (SPs) for each drug were calculated using the toxicity predictor, a machine-learning model. Univariate analysis extracted NRs and SPs associated with hiccups, and a multivariate analysis was performed to evaluate independent factors. Transforming growth factor-beta and antioxidant response element were considered an independent factor for hiccups in the male and female subgroups, respectively. This report first examined one of the mechanisms of drug-induced hiccups and identified MIEs associated with drug-induced hiccups.

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.

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, specially, in patients under-lying pre-existing renal function impairment, cardiovascular disease or diabetes that could rap-idly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network) and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on tra-ditional “gold standard” biomarkers known as serum creatinine, glomerular filtration rate and urinary output, new reliable serum and urinary biomarkers are still needed for an effective uni-fied diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination, as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Mucosal vaccines can target specific mucosal surfaces, such as the respiratory, genital, or intestinal mucosa. Conventional systemic immunization, such as intramuscular injections, do not provide mucosal immunity, including IgA, nor do they prevent pathogens from entering the mucous membranes. Nasal immunization protects mucosal membranes, but nasal antigen presentation appears to entail adjuvant to stimulate immunogenicity. Current treatments for mucosal diseases such as inflammatory bowel disease (IBD) and allergic dermatitis only aimed to temporarily relieve symptoms. Moreover, these treatments not only have drug resistance or side effects, but the disease can recur, leading to switching to other treatments. Therefore, there is a need to develop safe and effective treatments that provide better long-term outcomes to reduce the risk of recurrence. Regulatory T (Treg) cells have been used to suppress inflammation. To find advances in mucosal treatment, we investigated the therapeutic effects of intranasal pep27 mutant immunization. Here, a new method of Treg induction through intranasal immunization without adjuvant has been developed to potentially overcome allergies and mucosal inflammation of the lung-gut axis in animal models. The implementation of the pep27 mutant for these therapies should be preceded by studies of Treg resilience through clinical translational studies of dietary changes.

The worldwide competition to vaccinate against COVID-19 has highlighted the importance of immunization measures in containing the virus. Saudi Arabia, like the rest of the globe, must assess socio-demographic subtleties, chronic illnesses, vaccination effects, and public health policy implications as it navigates this complicated environment. This cross-sectional study examined Saudi COVID-19 vaccine in many ways. It examined the socio-demographic makeup of vaccine recipients, the prevalence of chronic conditions in this population, vaccine administration patterns, post-vaccination side effects, and vaccine-infection rates. A questionnaire-based online survey of 401 participants ensured gender, nationality, age, weight, and educational diversity. We analyzed vaccine manufacturer choice for each dosage, side effects after the first and second doses, and chronic diseases in the sample. Pfizer/BioNTech vaccines are preferred for all three doses, reflecting worldwide vaccination acceptance patterns. Side effects were not significantly different between vaccination kinds. Interestingly, immunization reduced infection rates, demonstrating the efficacy of COVID-19 vaccines. The data fills important information gaps and illuminates Saudi COVID-19 vaccination kinetics. These data support the global preference for mRNA vaccines, demonstrating the faith in this breakthrough technology. They also sponsor COVID-19 vaccine safety and effectiveness studies. The dramatic drop in infection rates among vaccinated people shows how vaccinations suppress the pandemic. These findings inform Saudi Arabia's immunization efforts. As booster doses become more common, long-term vaccination research is crucial. Vaccine reluctance, especially in certain demographics, must be addressed. Due to vaccines' protective potential, equitable vaccine distribution and large immunization programs are essential for herd immunity and pandemic management. This thorough cross-sectional study helps policymakers and healthcare practitioners build successful and inclusive COVID-19 immunization regimens in Saudi Arabia.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

This study concerns calculation and comparison of Fe, Co, Ni and Cu deposition rates in tungsten codeposition process based on electrodeposition of numerous tungsten alloys. 8 different tungsten alloys containing from 2 to 5 metals were electrodeposited in constant conditions in order to compare exact reduction rates. Calculated rates enabled control of the alloy composition precise enough to obtain a high-entropy WFeCoNiCu alloy with well-balanced composition. Introduction of copper to form the quinternary alloy was found to catalyze the whole process, increasing deposition rates of all components of the high-entropy alloy.