Childbirth education classes represent an antenatal tool for supporting pregnant women and couples in increasing knowledge on pregnancy, delivery, breastfeeding, and newborn care. The aim of this study was to investigate the impact of the additional lesson to the prenatal course regarding the advantage of the vaccination on mitigation of maternal anxiety. An observational study was designed including participants in childbirth education classes, comparing courses enhanced by the extra lesson on vaccination during pregnancy versus those lacking it. Assessment of the impact of prenatal educational on vaccine was measured by using validated questionnaires (State-Trait Anxiety Inventory, STAI; Perceived Stress Scale, PSS; World Health Organization- Five Well-Being Index, WHO-5). A total of 145 pregnant women participated to the investigation by answering to the online survey. Of them, 33 patients (22.8%) belong to the course without lesson on vaccine, while 112 (77.2%) participated to online prenatal education inclusive of additional meeting on usefulness to get vaccinated during pregnancy. No statistical differences were found between study groups in demographics and perinatal outcomes. Participants to enriched course reported lower basal anxiety levels than those without lesson on vaccine (STAI-State, normal score <40, 30 vs. 19%, p-value 0.041; STAI-State, mild score 40-50, 78 vs 67%, p-value 0.037). With reference to the last two weeks, maternal wellbeing level was improved by the added class (score >13 as measurement of wellbeing: 62% vs 80%, p-value<0.05). Moderate perceived stress assessed by PSS was found in those pregnant women without prenatal education on vaccine (64 vs 50%, p-value 0.042). The introduction of a lesson regarding on vaccination during pregnancy in the program of prenatal education courses improves maternal anxiety levels and wellbeing, in addition to reducing perceived stress.

Henipaviruses are single-stranded RNA viruses that have been shown to be virulent in several species including humans, pigs, horses, and rodents. Isolated nearly 30 years ago, these viruses have been shown to be of particular concern to public health, as at least two members (Nipah and Hendra viruses) are highly virulent, as well as zoonotic, and are thus classified as BSL4 pathogens. Although only 5 members of this genus have been isolated and characterized, metagenomics analysis using animal fluids and tissues has demonstrated the existence of other novel henipaviruses, suggesting a far greater degree of phylogenetic diversity than currently known. Using a variety of molecular biology techniques, it has been shown that these viruses exhibit varying degrees of tropism, on a species, organ/tissue, and cellular level. This review will attempt to provide a general overview of our current understanding of henipaviruses, with particular emphasis on viral tropism.

In this article, ‎we examine an allocation issue faced by European Health Union (EHU)‎. ‎Given this situation, ‎we introduce the issue of vaccine selection. ‎The model proposed in this paper helps to implement vaccination optimally using matching theory. ‎By adopting the mechanism presented in this article, ‎this is done more easily and more quickly, ‎so that mortality in society is lower and public satisfaction is increased. ‎This is similar to the issues analyzed in the literature on the design mechanism of non-perishable goods.

Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 among healthy children to those of VarivaxTM (control). Children aged 12 months to 12 years were randomized 1:1 to receive either NBP608 or control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. A total of 499 participants (NBP608, n = 251; control, n = 248) was enrolled. The seroconversion rate (SCR) measured using FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for SCR difference (NBP608 minus control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of –15%. In assessment by gpELISA, the SCR was 99.53% in the NBP608 group; and the 95% LCL for SCR difference was 6.5%, which was higher than the specified non-inferiority margin of –15%. There were no significant differences between the NBP608 and control group with respect to proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to VarivaxTM.

Data on immunogenicity, immune response persistency, and safety of COVID-19 boosters in patients with comorbidities are limited. Therefore, we aimed to evaluate and compare three different boosters in individuals who received two doses of the BBIBP-CorV vaccine including underlying diseases and healthy cases as control. One hundred forty subjects including 63 ones with at least one of three underlying diseases (UD) (including obesity, hypertension, and diabetes mellitus) and 77 healthy ones (HC) who had received a booster dose (either PastoCovac Plus or PastoCovac or BBIBP-CorV) were enrolled. The presence of SARS-CoV-2 antibodies was assessed before the booster injection and 28, 60, 90, and 180 days after it. Moreover, the adverse events (AEs) were recorded on days 7 and 21 post-booster shot for evaluating safety outcomes. Significantly increased titers of anti-spike, anti-RBD, and neutralizing antibodies were observed in both UD and HC groups 28 days after the booster dose, although the titer rise of anti-spike IgG and anti-RBD IgG was insignificantly inferior in the UD group compared to the HC group. All antibodies’ titers declined, with no significant differences between the two groups over time. Notably, all specific antibodies persisted up to 180 days; particularly the neutralizing antibody in both groups. Furthermore, no significant difference in antibody levels was observed between each UD subgroup and the HC group, except for neutralizing antibodies in the hypertension sub-group. PastoCovac Plus and PastoCovac boosters induced higher antibodies’ fold rise in UD individuals than BBIBP-CorV booster recipients. Safety outcomes did not show any serious AEs after the booster injection. The overall incidence of AEs post the booster injection was higher in the UD group than the HC group. Furthermore, the highest systemic AEs rate was reported in the UD group receiving the BBIBP-CorV booster. In conclusion, administration of COVID-19 boosters can equally induce robust and persistent humoral immune responses in individuals with or without UD primarily vaccinated with 2-doses of the BBIBP-CorV. Protein-based boosters with higher antibodies' fold rise and lower AEs in individuals with comorbidities might be considered a better choice for these individuals.

Recently, two respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We developed and validated an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and choice of blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM, respectively, showed high coefficients of determination (r2 = 0.90). Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r2 = 0.90) and SC-TM (r2 = 0.86). Further, both antigens showed high precision (coefficient of variation &lt; 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM but not with the attachment protein.

Feline infectious peritonitis (FIP), caused by the feline coronavirus (FCoV), is a devastating dis-ease in cats. Based on its antigenicity, FCoV can be divided into two serotypes: FCoV-I and FCoV-II. Furthermore, according to its pathogenicity, FCoV can be divided into feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). There are numerous factors that affect the pathogenesis of FIP, among which host immunity and viral genetics can play an es-sential role in the development of FIP. Owing to the lack of specific symptoms, existing individual diagnostic methods can only support the suspicion of FIP, and multiple diagnostic methods and test data need to be combined to make a diagnosis. Although there are still no effective FIPV vaccines or commercial drugs available in the market, various studies have shown that some compounds can be used for treatment. Therefore, FIP is no longer incurable in cats

In comparison to the general population, lung cancer patients are more likely to suffer from severe Coronavirus disease (COVID-19) and mortality associated with it. Considering this increased risk, and in order to prevent symptoms and severe disease, patients with lung cancer have been prioritized for COVID-19 vaccinations, primary and booster doses. Despite this, the pivotal clinical trials did not include these patients, which leaves open questions regarding vaccine efficacy and humoral immune response. This review outlines the findings of recent investigations into the humoral responses of lung cancer patients to COVID-19 vaccination, particularly the primary doses and first boost.

Background: Human papillomavirus (HPV) is responsible for most cervical cancer cases globally, with women living with HIV at higher risk of persistent HPV infection and HPV-associated disease. The HPV vaccine is a promising solution to reducing cervical cancer rates, but its uptake among women living with HIV in Nigeria is unknown. Methods: A facility-based, cross-sectional survey was conducted with 1,371 women living with HIV to assess their knowledge of HPV, cervical cancer, and the HPV vaccine, as well as their willingness to pay for the vaccine at the HIV treatment clinic, Nigerian Institute of Medical Research, Lagos. Willingness to pay for the HPV vaccine was also assessed. Multivariable logistic regression models were developed to identify factors associated with willingness to pay for the HPV vaccine. Results: The study found that 79.1% of participants had not heard of the vaccine, and only 29.0% knew of its efficacy in preventing cervical cancer. Moreover, 68.3% of participants were unwilling to pay for the vaccine, and the average amount they were willing to pay was low. Knowledge of HPV, the HPV vaccine, cervical cancer, and income were factors associated with willingness to pay for the vaccine. Health workers were the primary source of information. Conclusion: The study found that 79.1% of participants had not heard of the vaccine, and only 29.0% knew of its efficacy in preventing cervical cancer. Moreover, 68.3% of participants were unwilling to pay for the vaccine, and the average amount they were willing to pay was low. Knowledge of HPV, the HPV vaccine, cervical cancer, and income were factors associated with willingness to pay for the vaccine. Health workers were the primary source of information.

COVID-19 infection in the pediatric population usually leads to a mild illness, however, a rare but serious complication of MIS-C has been seen in children. MIS-C usually presents 2-4 weeks after COVID-19 infection or exposure, and rare reports have been documented in neonates. Vaccinations for COVID-19 have been approved for children 6 months and above in the United States, and recent reports suggest significantly low prevalence and risk of complications of MIS-C in vaccinated children compared to unvaccinated children. Vaccinations for COVID-19 are safe and recommended during pregnancy and prevent severe maternal morbidity and adverse birth outcomes. Evidence from other vaccine-preventable diseases suggests that through passive transplacental antibody transfer, maternal vaccinations are protective against infections in infants during the first 6 months of life. Various studies have demonstrated that maternal COVID-19 vaccination is associated with the presence of anti-spike protein antibodies in infants, persisting even at 6 months of age. Further, completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy is associated with reduced risk for COVID-19–associated hospitalization among infants aged 6 months or less. Therefore, it can be hypothesized that maternal COVID-19 vaccination can reduce the risk of and severity of MIS-C in infants. In this article, we review the literature to support this hypothesis.

Severe Acute Respiratory Syndrome Coronavirus 2 commonly known as SARS-CoV-2 is the utmost challenging pandemic that attracted scientific community to discover therapeutics as well as vaccination solutions to control SARS-CoV-2. Different diagnostic and detection methods have been improved and re-introduced from the previous observations of SERS and MERS. Due to the high mortality rate and fast spread, researchers all around the globe gathered to develop an effective vaccine. The review article summarizes various types of vaccines, mutants of virus, strategies in tackling virus, vaccine development and its global distribution with the focus on the use of mix and match of vaccines to fight the virus. The reported studies depict the design and production of successful COVID-19 vaccines with good efficacy as the selected vaccine population embrace high-risk personages i.e. above the age of 60, frontline workers and other essential service workers. We have targeted at delivering an outline of the determinations devoted to an effectual vaccine for novel Covid-19 that has restricted the domain by means of human health, economy, as well as life.

The poultry industry is affected by many epidemics and Newcastle Disease (ND) is a constant threat, known as a devastating disease for poultry farmers around the world. According to the average death time of chicken embryos, virus strains can be classified as lentogenic, mesogenic, or velogenic. The current research will clarify the vulnerable host range as well as the epidemiology and geographic distribution of ND in Pakistan. The introduction of the virus into poultry can have serious economic consequences, including the loss of production of sick and dying poultry, the cost of control measures (such as population reduction and disinfection measures), and possible trade restrictions in the event of an outbreak. The virus is transmitted by direct contact with sick poultry or carriers. Infected birds can also spread the virus in their feces. It can also be spread through respiratory secretions, contaminated feed, equipment, water, or feces. We will also discuss vaccines that which vaccines are available for NDV in Pakistan and vaccines can fight against this disease or not? In this study, a qualitative risk analysis was carried out to assess Pakistan's vulnerability to the introduction of virulent NDV strains

ABSTRACT. In this paper, we suggest a biomathematical numerical method for analysing mRNA nucleotides sequences based on UA/CG Fibonacci numbers proportions. This method is used to evaluate then compare the spike genes related to the main SARS-CoV2 VARIANTS currently circulating within the world population. The 10 main results proposed to be reproduced by peers are: 1/ SARS-CoV2 genome and spike evolution in one year 2020-2021. 2/ SARS-CoV2 Origins. 3/ Comparing 11 reference variants spikes. 4/ analysing 32 CAL.20C California variant patients spikes. 5/ Toward a meta mRNA Fibonacci gene end message code. 6/ Analysing S501 UK, S484 South Africa and « 2 mutations » INDIA variants. 7/ Suggesting a possible variants spike mRNA palindrome symmetry metastructure improving mRNA stability then infectiousness. 8/ Analysing Fibonacci Metastructures in the mRNA coding for the vaccines PFIZER and MODERNA. 9/ Does the CG-rich modification of the synonymous codons of the spikes of the 2 mRNA vaccines affect the expression and quantity of SARS-CoV2 antibodies? 10/ The exceptional case of the Brazilian variant P.1. Particularly, we suggest the following conjecture at mRNA folding level : CONJECTURE of SARS-CoV2 VARIANTS: The growth of long Fibonacci structures in the shape of "podiums" for almost all of the variants studied (UK, California, South Africa, India, etc.) suggests the probable folding of the Spike mRNA in the form of a "hairpin", which can strengthen the cohesion and the lifespan of this mRNA. Finally, we show that these kinds of Fibonacci matastructures disapear TOTALLY by analysing the published mRNA sequences of PFIZER and MODERNA vaccines. One fact is certain, the two mRNAs of the Moderna and Pfizer vaccines will result in a low functionality of the spike vaccine. This is because their designers by seeking greater stability, have doped to build CG rich sequences which, as soon as they are inserted into the human host, will, paradoxically, seek to mutate, like SARS-CoV2 variants, towards CG ==> UA forms in order to improve their STABILITY and LIFETIME. We conclude using new biomathematics theoretical methods (Master code and numerical standing waves), and comparing the Spikes of the two vaccines Moderna and Pfizer, that there will be very probable differences in stability and shelf life of the two respective mRNAs vaccines. However, “State of the Art” analyzes will disclose that their two protein sequences are strictly identical. By modified their synonymous codons using different strategies, no one can guarantee that the quantity of antibodies generated will be identical in the two cases. We wish to draw attention to the great ADAPTATION power - at the global scale of their genomes - of the most infectious VARIANTS, such as the BRAZIL 20J / 501Y.V3 variant (P.1). This is very worrying for the VACCINES <==> VARIANTS run: We demonstrate how the Brazilian variant P.1 which becomes uncontrollable in Brazil in April 2021 has a level of organization of long metastructures of 17,711 bases covering the genome which is 3.6 more important than that of the 2 reference genomes SARS-CoV2 and worldwide D614G. We suggest that this high level of overall structure of this variant contributes to the stability of this genome and, might explain its greater contagiousness.

Rapid online surveys are an important tool in tracking the public’s knowledge and perceptions during infectious disease outbreaks. In June 2020, during the early phases of COVID-19 vaccines development, a survey had been conducted, aimed at assessing attitudes and opinions about vaccination of 885 Italian adults, in addition to their vaccine literacy levels (i.e. skills of finding, understanding and using information about vaccines). In January 2021, the same questionnaire has been administered to a similar population (n=160). Interactive vaccine literacy was significantly higher than in June 2020 (mean score 3.38 vs 3.27 respectively, P=.0021). The percentage of participants willing to be vaccinated against COVID-19 was assessed by the means of either-or questions, and was equally high in both surveys (>90%), which is quite reassuring, despite metrics based on categorical scales cannot identify hesitant subjects.

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific western blot analysis detected anti-NS1 antibodies also in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

Lassa virus (LASV) is responsible for a type of acute viral haemorrhagic fever referred to as Lassa fever. Lack of adequate treatment and preventive measures against LASV resulted in a high mortality rate in its endemic regions. In this study, a multi-epitope vaccine was designed using immunoinformatics as a prophylactic agent against the virus. Following a rigorous assessment, the vaccine was built using T-cell (N_CTL=8 and N_HTL=6) and B-cell (N_LBL=4) epitopes from each LASV-derived protein with suitable linkers and adjuvant. The physicochemistry, immunogenic potency and safeness of the designed vaccine (~68 kDa) were assessed. In addition, chosen CTL and HTL epitopes of our vaccine showed 97.37% worldwide population coverage. Besides, disulphide engineering also improved the stability of the chimeric vaccine. Molecular docking of our vaccine protein with toll-like receptor (TLR2) showed binding efficiency followed by dynamic simulation for stable interaction. Furthermore, higher levels of cell-mediated immunity and rapid antigen clearance were suggested by immune simulation and repeated-exposure simulation, respectively. Finally, the optimized codons were used in in silico cloning to ensure higher expression within E. coli K12 bacterium. With further assessment both in vitro and in vivo, we believe that our proposed peptide-vaccine would be potential immunogen against Lassa fever.

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

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 &gt;0 FISVIN &lt;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 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.

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.

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.

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.

To investigate the associated mechanisms concerning collagen and the expression of apoptosis-related proteins in porcine skin injuries induced by laser exposure, pig skin was treated with a 1064 nm laser. The healing process of the laser-treated areas, alterations in collagen structure, and changes in apoptosis were continuously observed and analyzed from 6 hours to 28 days post-irradiation. On the 28th day following exposure, wound contraction and recovery were notably sluggish in the medium-high dose groups, displaying more premature and delicate type III collagen within the newly regenerated tissues. The collagen density in these groups was roughly 37-58% of that in the normal group. Between days 14 and 28 after irradiation, there was a substantial rise in apoptotic cell count in the forming epidermis and granulation tissue of the medium-high dose group, in contrast to the normal group. Notably, the expression of proapoptotic proteins bax, caspase-3, and caspase-9 surged significantly 14 days after irradiation in the medium-high dose groups and persisted at elevated levels on the 28th day. During the later stage of wound healing, the augmented apoptotic cell population and insufficient collagen generation in the newborn skin tissue of the medium-high dose groups were closely associated with delayed wound recovery.

Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM). Sixty male C57BL/6J mice were divided initially to two groups, the shifted group (n=30) exposed to circadian shifts for three months and the non-shifted group (n=30) under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 hour light-dark cycle followed by another five days under reversed light-dark cycle. At the end of the three months a colitis was induced by 2 % DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n=15 per group), sham group non-shifted (Sham-NS), sham group shifted (Sham-S) and DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition by DNA extraction followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, GM composition was also modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings shows a possible interplay between circadian rhythm disruption, GM dynamics, and colitis pathogenesis.

Silkworm ovary-derived BmN4 cells rely on chromatin-induced spindle assembly to form microtubule-based square mitotic spindles that ensure accurate segregation of holocentric chromosomes during cell division. The chromosome passenger protein Aurora B regulates chromosomal condensation and segregation, spindle assembly checkpoint, and cytokinesis; however, its role in holocentric organisms needs further clarification. This study examined the architecture and dynamics of spindle microtubules during prophase and metaphase in BmN4 cells and those with siRNA-mediated BmAurora B knockdown using immunofluorescence labelling. Anti-α-tubulin and anti-γ-tubulin antibodies revealed faint γ-tubulin signals co-localized with α-tubulin in early prophase during nuclear membrane rupture, which intensified as prophase progressed. At this stage, bright regions of α-tubulin around and on the nuclear membrane surrounding the chromatin suggested the start of microtubule assembling in the microtubule organizing centers (MTOCs). In metaphase, the number and size of γ-tubulin foci increased and were detected on both sides of the chromosomes. This resulted in a distinctive multipolar square spindle with holocentric chromosomes aligned at the metaphase plate. siRNA-mediated BmAurora B knockdown significantly reduced the γ-tubulin foci during prophase, impacting microtubule nucleation and spindle structure in metaphase. Spatiotemporal BmAurora B expression analysis provided new insights into the regulation of this mitotic kinase in silkworm larval gonads during gametogenesis. Our results suggest that BmAurora B is crucial for the formation of multipolar square spindles in holocentric insects, possibly through the activation of γ-tubulin ring complexes in multiple centrosome-like MTOCs.

(1) Background: National health system databases represent one of the most obvious sources of information about epidemiology of adverse drug reactions including drug-induced allergy and anaphylaxis. (2) Methods: Retrospective analysis of data from national database of pharmacovigilance in the Russian Federation (analyzed period 02.04.2019 - 21.06.2023) was performed. The prevalence of anaphylactic reactions (ARs) was determined, the structure of drugs involved was estimated together with patients’ characteristics. (3) Results: ARs were reported in 8.3% of drug-induced allergic reactions (2304/27,727), mean age of patients was 48.2 ± 15.8 years, 53.2% were females. Main causative groups of drugs were antibiotics, ABs (44.62%), local anesthetics, (19.97%), and cyclooxygenase (COX)-inhibitors (10.07%). Fatal ARs was reported in 9.5% (218/2304), mean age 48.0 ± 16.7 years, 56.2% females. Pediatric population accounted for 5.8% (133/2304), mean age 11.8± 4.5 years, 51.9% females. Elderly population accounted for 2.8% (65/2304), mean age 73.0±5.3 years, 43.5% (27/65) females. ABs were the leading causative groups of ARs in the elderly (40%), children (42.86%), and among fatal cases (50%). (4) Conclusions: ARs accounted for 8.3% of all drug-induced allergic reactions, and ABs were the most common causative agents. Females predominated in all groups except elderly patients.

The oscillation of an elastically mounted rigid cylinder excited by steady fluid flow is investigated. Regarding the nonlinearity of real practical structures like marine risers and the stay cable of a long-span bridge, the dynamic behavior of the circular cylinder is described by double Duffing equations and the aerodynamic force performance of the wake flow is expressed by wake oscillator equation. Unlike previous studies, in the present investigation, attention is focused on coupling the wake oscillator equations, taking into account quadratic terms. Following this approach, the cylinder's combined cross-flow and in-line Vortex-Induced Vibrations (VIV) are modeled more accurately. Empirical coefficients are adjusted through comparison with previous credible experimental studies and the effects of changing coefficients of the quadratic terms on major VIV parameters are investigated. The oscillating amplitude calculated by the present model is close to that of the experiment. The relative error of results obtained by the present coupled model is lower than the previous model. Moreover, the present model successfully predicts the moving trajectories of a circular cylinder under VIV in a figure-of-eight shape.

Legumes play a significant role in the alleviation of food insecurity, maintaining soil fertility and achieving sustainable crop production under adverse environmental conditions. The increased demand in legume production contemplates that attention on the genetic improvement of these crops through various means such as genetic engineering and mutation breeding should take a centre stage in global agriculture. Therefore, this paper provides succinct analysis of currently available literature on morphological and physiological traits in polyploidised leguminous plants to counter the adverse effects of drought stress. The effects of colchicine on various morphological and physiological traits of polyploidised legumes compared to their diploid counterparts were examined. Numerous reports revealed variations in these traits such as improved root and shoot growth, plant biomass, chloroplastidic content, protein, RNA and DNA. The differences observed were also associated with the strong relationship between plant ploidy-induction and colchicine application. Furthermore, the analysis indicated that polyploidisation remains dose-dependent, and may be achievable at a shorter space of time as this antimitotic chemical interferes with chromosome separations in somatic plant cells. The efficiency of this process also depends on the advancement of treatment conditions (in vitro, in vivo or ex vitro) and successful regeneration of polyploidised plants for adaptation under drought stress conditions. As such, the improvement in metabolite profile and other essential growth characteristics serves as a clear indication that induced polyploidy needs to be further explored to confer resilience to environmental stress, and improve crop yield under drought stress conditions in leguminous plants.

Background: Muscle wasting is a common phenomenon in oncology and appears to be alleviated by exercise training. This study aims to determine the degree of aggressiveness of cancer-induced muscle wasting in two different phenotypic muscles, and whether exercise training can attenuate this muscle dysfunction. Methods: Fifty Sprague-Dawley rats were randomly assigned to four experimental groups, two control groups (sedentary and exercised) and two breast cancer model groups (sedentary and exercised) induced by 1-methyl-1-nitrosoureia (MNU). After 35 weeks of endurance training the animals were sacrificed and the gastrocnemius and soleus muscles were harvested for morphometric analysis. Results: A significant reduction in cross-sectional area (P < 0.05) was found in both muscles of sedentary tumor-bearing animals. Interstitial fibrosis was significantly higher in the gastrocnemius of sedentary tumor-bearing animals (P < 0.05), but not in the soleus. A shift from large to small fibers was observed in the gastrocnemius of sedentary tumor-bearing animals. Long-term exercise training was able to prevent this cancer-related mus-cle dysfunction. Conclusions: The Gastrocnemius muscle showed a very pronounced reduction in cross-sectional area and marked interstitial fibrosis in sedentary animals with tumors. The soleus muscle showed a less pronounced but significant reduction in cross-sectional area, and collagen deposition did not differ between tumor groups. These contrasting results confirm that can-cer-induced muscle wasting can affect specific fiber types, and specific muscles, namely fast glycolytic muscles, and that exercise training can act to improve it.

Epithelial cells can undergo apoptosis by manipulating the balance between pro-survival and apoptotic signals. In this work, we show that TRAIL-induced apoptosis can be differentially regulated by the expression of α(1,6)fucosyltransferase (FucT-8), the only enzyme in mammals that transfers the (1,6)fucose residue to the pentasaccharide core of complex N-glycans. Specifically, in the cellular model of colorectal cancer (CRC) progression formed using the human syngeneic lines SW480 and SW620, knockdown of the FucT-8-encoding FUT8 gene significantly enhanced TRAIL-induced apoptosis in SW480 cells. However, FUT8 repression did not affect SW620 cells, which suggests that core fucosylation differentiates TRAIL-sensitive premetastatic SW480 cells from TRAIL-resistant metastatic SW620 cells. In this regard, we provide evidence that phosphorylation of ERK1/2 kinases can dynamically regulate TRAIL-dependent apoptosis and that core fucosylation can control the ERK/MAPK pro-survival pathway in which SW480 and SW620 cells participate. Moreover, the depletion of core fucosylation sensitises primary tumour SW480 cells to the combination of TRAIL and low doses of 5-FU, oxaliplatin, irinotecan or mitomycin C. In contrast, combination of TRAIL and oxaliplatin, irinotecan or bevacizumab reinforces resistance of FUT8-knockdown metastatic SW620 cells to apoptosis. Consequently, FucT-8 could be a plausible target for increasing apoptosis and drug response in early CRC.

When there are multiple key strata in the overburden of deep coal seam and the surface subsid-ence coefficient after mining is small, it indicates that the overlying key strata fail to break com-pletely after mining. On this occasion, the stress concentration on the working face occurs easily, which in turn leads to the occurrence of dynamic disasters such as rock burst. This study adopted a comprehensive analysis method of field monitoring and numerical simulation to explore the in-fluence of key stratum on the evolution law of mining-induced stress in the working face. Dis-tributed optical fiber sensor (DOFS) and surface subsidence GNSS monitoring system were re-spectively arranged inside and at the mouth of the ground observation borehole. According to the monitoring results of strain obtained from DOFS, the height of broken stratum inside the overlying strata was obtained; according to the monitoring results of surface subsidence, the sur-face subsidence coefficient was proved to be less than 0.1, indicating that the high key stratum does not break completely, but enters a state of bending subsidence instead. In order to reveal the influence of key stratum on the mining-induced stress of working face, two 3DEC numerical models with and without key stratum were established for comparative analysis. As the numeri-cal simulation results show, when there are multiple key strata in the overburden, the stress in-fluence range and stress concentration coefficient of coal seam after mining are relatively large. The study revealed the working mechanism of rock burst accidents after large-scale mining and predicted the potential area of rock burst risk after the mining of the working face, which has been verified by field investigation. The research results are of great guiding significance for the revelation of the working mechanism of rock burst in deep mining condition and its prevention and control.

Potato tubers are susceptible to wounding during post-harvest processes, leading to quality decline, perishability and large economic losses. In this study, the potato cultivar, ‘Longshu No.7’, was foliar-sprayed with 3% chitosan (w/v) three times during the pre-harvest period after flowering to evaluate the effect of foliar spraying with chitosan on suberization processing at wounds of harvested potato tubers. Our results demonstrate that foliar-sprayed with chitosan significantly reduced wound-induced fresh weight loss and dry rot disease index by 37.34% and 41.60% on the 28 day after wounding, respectively. Foliar-sprayed with chitosan accelerated the deposition of suberin polyphenolics and lignin at the wound sites of potato tubers with the formation of thicker cell layers. This occurred with increased localized activities of key enzymes in the suberin polyphenolics and lignin pathways, including phenylalanine ammonia lyase, 4-coumaryl-coenzyme A ligase, cinnamyl alcohol dehydrogenase and peroxidase (33.90–64.32%), as well as the contents of cinnamic acid, sinapic acid, flavonoids, lignins and total phenolics (19.70–23.46%) at wound sites of potato tubers on the 7 day after wounding. Our results indicated that foliar application of chitosan accelerated wound-induced suberization of potato tubers and could mitigate post-harvest product damages.

Here we investigated the acute effects of an exhaustive intermittent exercise session on immunological parameters of the elderly and the subsequent incidence of upper respiratory tract infections and compare with the moderate-intensity. To do so, ixty-three old subjects were divided into three groups HIIT (n=21) submitted at one High-intensity interval training, SCG (n=21) kept in a sedentary state, and MICT (n=21) submitted at moderate intensity walking. Blood were collected at 5 time points, before, immediately after, 2h, 24h, and 48h after the intervention. In result the IL-6 and TNF-α were overexpressed immediately after the IL-10 stood overexpressed and correlated with IL-17, denoting an inflammatory process, and evidencing an immunologic competence without enhancement of the prevalence of upper respiratory infection tract (URTIs). So a modulation in the balance of Th1/Th2/Th17 cytokines and leukocytes, these modifications did not cause the effect characterized as an immunological window. Perhaps, the typical inflammation process, with IL-10 and IL-17 participation could also produce benefits to combat infections, a pertinent discussion during a post-pandemic time; we consider it a safe exercise program for older adults.

The polygenic and multifactorial nature of many psychiatric disorders has hampered the personalized medicine approach implementation in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into induced pluripotent stem cells (iPSCs) to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that recapitulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depression disorder, bipolar disorder, and autism spectrum disorder. The future perspective will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways to build a disease model that considers individual variability and tailors personalized treatments.

Chemotherapy-induced peripheral neuropathy (CIPN) develops as a challenging nerve-damaging adverse effect of anticancer drugs used in chemotherapy. The disorder may require a dose reduction of chemo-therapy and its most common sensory symptoms are severe pain, tingling, and numbness in the hands and feet. CIPN affects dramatically the patient's quality of life (QoL). Pain and sensory abnormalities may occur for months, or even years after the termination of chemotherapy. This disease has complicated pathophysiology featured by underlying mechanisms not completely known. Although many pharmaco-logical and non-pharmacological therapeutic approaches have been tested to overcome these symptoms, there is currently no standardized cure to prevent or treat CIPN. According to current guidelines, Duloxe-tine is the only recommended agent for painful neuropathic symptoms. Therefore, finding effective thera-pies for CIPN is mandatory. The purpose of this review is to dissect CIPN, the target and immunothera-py-based approaches to this disorder, as well as to offer new insights for novel therapeutic perspectives.

Seismic monitoring in areas where induced earthquakes could occur is a challenging topic for seismologists due to generally very low signal to noise ratio. Therefore, the seismological com-munity is devoting several efforts to the development of high-quality networks around the areas where fluid injection and storage and geothermal activities take place, also following the national induced seismicity monitoring guidelines. The use of advanced data-mining strategy, such as template matching filters, auto-similarity search and deep-learning approaches is recently further fostering such a monitoring enhancing the seismic catalogues and lowering the magnitude of completeness of these areas. In this framework, we carried out an experiment where a small-aperture seismic array was installed around the gas reservoir of Collalto, in North Italy. The continuous velocimetric data, acquired for 25 days, were analysed through the application of the optimized auto-similarity search technique FAST. The array was conceived as a cost-effective network, aimed at integrating, right above the gas storage site, the permanent high-resolution Collalto Seismic Network. The analysis allowed to detect micro-events down to magnitude Ml=-0.4 within a distance of ~15km from the array. Our results confirmed that the system based on the array installation and the FAST data-analysis might contribute to lower the magnitude of completeness around the site of about 0.7.

The development of gamma rays mutant rice lines would be a solution for introducing variability in already farmer using varieties. In vitro gamma (60Co) mutagenesis reduces chimeras and allows a faster selection of desired traits but requires laboratory process optimization. The objective of the present work was the in vitro establishment of a recalcitrant rice embryogenic calli, the determination of its sensitivity to gamma radiation (Co-60), sequencing MATK and Rubisco for identification purposes, as well as generation optimization. The radiosensitivity of embryogenic calli resulted in an LD50 of 110Gy, while the 20% lethal dose was 64Gy. All sequenced genes matched perfectly with already reported MATK and Rubisco O. sativa genes with a clear SNP that identifies the local variety related to the southeast Asia Region. Callus induction improves with an MS with 2mg/L 2,4D, and the regeneration was achieved with an MS medium with 3mg/L BAP and 0,5mg/L NAA. The optimized radiation condition was 60Gy with an 83% regeneration in a semisolid medium, allowing a balance between mutation and regeneration. When increased to 80Gy, the regeneration rate falls to 29%. An immersion system (RITA®) of either 60 or 120 seconds every 8hours allowed a systematic and homogeneous total regeneration of the recalcitrant line, in contrast with the semisolid medium that resulted in positive but irregular regeneration. Other well-known recalcitrant cultivars, CR1821, CR1113 also had an improving regeneration in the immersion system, demonstrating its potential use for recalcitrant materials. To our knowledge, this is the first report on using an immersion system to allow regeneration of gamma-ray mutants from recalcitrant rice materials.

The tri-trophic interactions between plants, insects, and insect predators and parasitoids are often mediated by chemical cues. The attraction to Herbivore-Infested Plant Volatiles (HIPVs) has been well documented for arthropod predators and parasitoids, and more recently for insectivorous birds. The attraction to plant volatiles induced by the exogenous application of methyl jasmonate (MeJA), a phytohormone typically produced in response to an attack of chewing herbivores, have provided controversial results, both in arthropod and avian predators. In this study, we aimed to examine whether potential differences in the composition of bouquets of volatiles produced by Herbivore-infested and MeJA-treated Pyrenean oak trees (Quercus pyrenaica) were related to differential avian attraction, as results from a previous study suggested. Results showed that the overall emission of volatiles produced by MeJA-treated and Herbivore-infested trees did not differ, and were higher than emissions of Control trees, although MeJA treatment showed more significant reaction and released several specific compounds in contrast to Herbivore-induced trees. These slight differences in the volatile composition may explain why avian predators were not so attracted to MeJA-treated trees as observed in a previous study in this plant-herbivore system. Unfortunately, the lack of avian visits to the experimental trees in the current study does not allow us to confirm this result and points out the need to perform more robust predator studies.

The inherent trace quantity of primary fatty acid amides found in biological systems presents challenges for analytical analysis and quantitation, requiring a highly sensitive detection system. The use of microfluidics provides a green sample preparation and analysis technique through small-volume fluidic flow through micron-sized channels embedded in a PDMS device. Microfluidics provides the potential of having a micro total analysis system where chromatographic separation, fluorescent tagging reactions, and detection are accomplished with no added sample handling. This study describes the development and optimization of a microfluidic-laser indued fluorescence (LIF) analysis and detection system that can be used for the detection of ultra-trace levels of fluorescently tagged primary fatty acid amines. A PDMS microfluidic device was designed and fabricated to incorporate droplet-based flow. Droplet microfluidics have enabled on-chip fluorescent tagging reactions to be performed quickly and efficiently, with no additional sample handling. An optimized LIF optical detection system provided fluorescently tagged primary fatty acid amine detection sub-fmol (436 amol) LODs. The use of this LIF detection provides unparalleled sensitivity, with detection limits several orders of magnitude lower than currently employed LC-MS techniques and might be easily adapted for use as a complementary quantification platform for parallel MS-based -omics studies.

Direct laser writing based on non-linear 3D nanolithography (also known as 3D laser lithography, 3DLL) is a powerful technology to manufacture polymeric micro-optical components. However, practical applications of these elements are limited due to the lack of knowledge of their optical resilience and durability. In this work, we employ 3DLL for the fabrication of bulk (i.e. fully filled) and woodpile structures out of different photopolymers. We then characterize them using S-on-1 laser induced damage threshold (LIDT) measurements. In this way, quantitative data of LIDT values can be collected. Furthermore, this method permits to gather damage morphologies. The results presented in this work demonstrate that LIDT values depend on the material and the geometry of the structure. Bulk non-photosensitized hybrid organic-inorganic photopolymer SZ2080 structures are found to be the most resilient with a damage threshold being of 169±15 mJ/cm².

Traditional winglets are designed as fixed devices attached at the tips of the wings. The primary purpose of the winglets is to reduce the lift-induced drag, therefore improving aircraft performance and fuel efficiency. However, because winglets are fixed surfaces, they cannot be used to control lift-induced drag reductions or to obtain the largest lift-induced drag reductions at different flight conditions (take-off, climb, cruise, loitering, descent, approach, landing, and so on). In this work, we propose the use of variable cant angle winglets which could potentially allow aircraft to get the best all-around performance (in terms of lift-induced drag reduction), at different flight phases. By using computational fluid dynamics, we study the influence of the winglet cant angle and sweep angle on the performance of a benchmark wing at Mach numbers of 0.3 and 0.8395. The results obtained demonstrate that by adjusting the cant angle, the aerodynamic performance can be improved at different flight conditions.

This work examines atomic and molecular signatures in laser-induced plasma in standard ambient temperature and pressure environments, including background contributions to the spectra that depend on the laser pulse-width. Investigations include solids, gases, and nano-particles. Abel inversions of measured line-of-sight data reveal insight into the radial plasma distribution. For nominal 6 nanosecond laser pulses and for pulse-energies in the range of 100 to 800 mJ, expansion dynamics and turbulence due to shock phenomena are elucidated to address local equilibrium details that are frequently assumed in spatially averaged emission spectroscopy. Chemical equilibrium computations reveal temperature dependence of selected plasma species. Specific interests include atomic hydrogen (H) and cyanide (CN). Atomic hydrogen spectra indicate axisymmetric shell structures and isentropic expansion of the plasma kernel over and above the usual shockwave. The recombination radiation of CN emanates within the first 100 nanoseconds for laser-induced breakdown in a 1:1 CO2:N2 gas mixture when using nanosecond laser pulses to create the micro-plasma. The micro-plasma is generated using 1064 nm, 150 mJ, 6 ns Q-switched Nd:YAG laser radiation. Measurements of the optical emission spectra utilize a 0.64 m Czerny-Turner type spectrometer and an intensified charge-coupled device.

The steady streaming (SS) phenomenon is gaining increased attention in the microfluidics community, because it can generate net mass flow from the zero-mean vibration. We developed numerical simulation and experimental measurement tools to analyze this vibration induced flow, which has been challenging due to its unsteady nature. Validity of these analysis methods is confirmed by comparing the three-dimensional (3D) flow field induced around a cylindrical micropillar under circular vibration. In the numerical modeling, we directly solved the flow in the Lagrangian frame so that the substrate with a micropillar becomes stationary, and the result was converted to the Eulerian frame to compare them with the experimental results. The present approach enables to avoid the introduction of moving boundary or small perturbation approximation. The flow field obtained by the micro particle image velocimetry (PIV) measurement supported the three-dimensionality observed in the numerical results, which could be important for controlling the mass transport and manipulating particulate objects in the microfluidic systems.

The resonance spectra of neutral silver indicate self-absorption for the studied Ag I lines at the wavelengths of 327.9 nm and 338.2 nm. The center dip is associated with self-reversal due to self-absorption in the plasma. The Q-switched radiation of 355 nm, 532 nm, or 1064 nm from a Nd:YAG laser device generates the plasma at the surface of silver nano-material targets, with experiments conducted in standard ambient temperature and pressure laboratory air. Procedures for recovery of the spectral line shapes confirm that over and above the effects of self-reversal, line shape distortion are important in the analysis. The work discusses parameters describing self-absorption when using fluence levels of 2 to 33 J/cm² to generate the plasma. Furthermore, subsidiary calibration efforts that utilize the hydrogen alpha line of the Balmer series show that the Ag I lines at 827.35 nm and 768.7 nm are optically thin.

Pre-existing fracture and secondary cracks in rock mass are formed by natural power, such as magma condensed to igneous rocks and tectonic movement. The orientation and inclination of these fractures obey certain laws relating to the stress, temperature, minerals, water and so on. Therefore, cracks react differently under the same external loading on the condition of various inclination, fissure apertures, stiffness and joint roughness. To simulate the crack propagation, experiments on hollow cylinder cut by one oblique interface mimicking single fracture accumulated numerous data discovering the failure criterion in accordance with the Mohr-Coulomb criterion. And theory on the Terzaghi’s effective principle take an essential role in controlling the behavior of triggering fault. This paper introduced a series of oblique plane cutting the cylinder regarded as fractures at different inclination to concentrate on how the fracture characteristics effect the stress and strain distribution inside the specimen, especially, the relationship between displacement and water head. The key point of this numerical simulation is coupling the solid phase and the fluid phase, specifically, the mechanic and seepage field. According to the statics, curves referring to deformation and water head could be described as increasing lines. Besides, simulation on coupling solid phase and fluid phase can supply crucial evaluation on activating existing fault, and thus predicting induced seismicity in reservoirs or estimating damage in shale gas exploration.

المستخلص تصنيع لقاح مكون من الحمض النووي الريبوزي الرسول الخاص بالبروتينات المسئولة عن انتاج البروتينات نيورامنيديز والهيم اجليوتونين لفيروسي الانفلونزا الخنازير والطيورمحاط بجزيئات دهنية بحجم النانوميتر عدوى انفلونزا الخنازير وانفلونزا الطيور مشكلة خطيرة تؤرق العالم كله هذه الايام خصوصا انها مميتة لكثير من اطفال العالم . بعد فترة التعافي من الاصابة تتكون المناعة المكتسبة ضدها لمدة عام تقريبا. هذه الانفلونزا تسبب تسمم فيروسي في الدم بالاضافة للالتهاب الرئوي وهذامن بين اكبرالاسباب للوفاة بين الاطفال قبل سن عامين عالميا بشكل مباشر. الهدف من الدراسة هو انتاج لقاح الحمض النووي الريبوزي الرسول من نوع الام بالنانوتكنولوجي لبروتينات الهيم اجليوتونين والنيورامنيديز الموجودة على سطح هذه الفيروسات التي تساعدتها في الاتصاق بالعائل الذي ستتكاثر داخل خلاياه بالجهاز التنفسي. هذه الدراسة دراسة استكشافية ومن خلالها استطاعنا تصميم هذا اللقاح باستعمال نظام توصيل للقاح بالنانوتكنولوجي حجم جزيئاته 70نانوميمتر. اللقاح الجديد اظهر فاعلية بنسبة 60% واظهر فاعلية حيوية مقاربة واثار جانبية اقل بالمقارنة باللقاحات المتوفرة حاليا بالسوق الدوائي ضد هذا النوع من الفيروسات الوبائية. ABSTRACT Background: Worldwide, Swine and Avian influenza, or the H1N1 and H5N1 serotypes of the Influenza A virus, is a highly contagious illness. In recent years, the global incidence of mortality rate has surpassed 284,000 fatalities. Aim of the study: The production of mRNA vaccine lipid nanoparticles (LNP) to combat the deadly strains of Avian and Swine influenza (H1N1 and H5N1 of the influenza A serotype). Methodology: Polymerase chain reaction (PCR) was used to clone genes of interest encoding Haemagglutinin (HA) and Neuraminidase (NA) of Influenza A virus strains (H5N1 and H1N1) known as Avian flu and Swine flu, respectively. The genes were then inserted using the EcoR1, BAM Hind II restriction endonuclease type II, and Ligase enzyme into the pET-21(+) transcription vector plasmid. On the other hand, the hybrid transcription vectors were mixed with T7 RNA polymerase and ribonucleotides within a test tube after being linearized using EcoR II. Following their purification via reversed-phase high-performance liquid chromatography (RP-HPLC), the mRNAs of the HA and NA were encased in 70 nm LNPs and subjected to reverse-phase high-performance liquid chromatography (RP-HPLC). Lastly, immunogenicity studies were performed in stages 1/2 of randomized human and preclinical clinical trials. Results: The bivalent vaccination had around 63% efficacy in preclinical studies and approximately 60% efficacy in randomized human clinical trials. As shown by the ELISA test, strong neutralizing antibodies against HA were prevalent. Conclusion: The current study is a promising effort because of the development of the novel LNP-mRNA vaccine, which could lower the incidence of Avian and Swine flu infectious disorders.

Introduction: Type 1 diabetes mellitus is a chronic disease of autoimmune etiology that is highly prevalent in childhood. In the last decade, the possibility of using the Bacillus Calmette-Guérin vaccine for the treatment of this disease has been studied thanks to its immunomodulatory action . Objectives: The objective of this work is to carry out a systematic review of the available scientific evidence on the relationship between the tuberculosis vaccine and the treatment of diabetes in childhood. Secondarily, the aim is to study the incidence of Type 1 Diabetes Mellitus in a cohort of children from the Basque Country according to whether or not they have received the vaccine. Methods: An exhaustive bibliographic search has been carried out on the evidence available to date. For the epidemiological study in Euskadi, a comparison of accumulated incidences between vaccinated and unvaccinated population groups was made. Results: According to the literature analyzed, There is more and more evidence about the possible use of the tuberculosis vaccine in Type 1 Diabetes Mellitus. The results of our study were not conclusive, but we believe that it is necessary to continue with long-term studies to eliminate biases. Conclusions: The Bacillus Calmette-Guérin vaccine could be used for the treatment of autoimmune, allergic, infectious or oncological processes, although more studies are still necessary in this regard.

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

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.

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

Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6] or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T cell epitope P2 (P2-VP8*) or expressed P2-VP8* as a fusion protein with lumazine synthase (LS-P2-VP8*) to allow the formation and secretion of protein particles that present VP8* on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as positive and negative control, respectively. Upon challenge with virulent Wa HRV, significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8*-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8*-specific IgG anti-body-secreting cells in ileum, spleen and blood seven days post-challenge as well as VP8*-specific IFN--producing T cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8* compared to P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for further development of mRNA-based rotavirus vaccines.

(1) Background: Various cutaneous adverse drug reactions (ADRs) are observed with the development of mRNA COVID-19 vaccines. To gain insight into the clinicopathologic features, we analyzed the correlation of histological and clinical data in 48 patients with these ADRs.; (2) Methods: Single-center retrospective study in patients with ADRs post-mRNA COVID-19 vaccination (mRNA-1273 and BNT162b2 vaccines).; (3) Results: Distant generalized ADRs prevailed (91%), often appearing clinically as spongiotic dermatitis or maculo-papular exanthema. Histopathological analysis revealed spongiotic changes (46%) and dermal superficial perivascular lympho-histiocytic infiltrates (17%). Eosinophils were found in 66% of biopsies, neutrophils in 29%, and plasma cells only in 8% of biopsies. Most ADRs occurred post-second vaccine dose (44%). Histologically spongiotic changes were associated with clinical features of spongiotic dermatitis in only 50% and maculo-papular exanthema in the remaining patients. ADRs represented an aggravation of preexisting skin disease in 23% of patients. ADRs regressed within 28 days or less in 53% of patients and persisted beyond a month in the remaining patients.; (4) Conclusions: Our study demonstrates a diverse spectrum of generalized ADRs, revealing correlations between histology and clinical features but also instances of divergence. The majority of ADRs are self-limited with a few extending beyond a month.

Background Glioblastoma (GBM) is a poor prognosis malignant grade 4 glioma. After surgical resection, standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. The DC vaccination increased the amount of intratumoral-activated cytotoxic T lymphocytes and decreased the number of FoxP3-positive regulatory T cells. Based on these da-ta, we have developed a phase II protocol with the DC vaccine concomitant to standard RT-CT in patients undergoing surgery for GBM. Methods This is a single-arm, monocentric, phase II trial evaluating progression-free survival (PFS) and the safety of a DC vaccination integrated with standard therapy in resected GBM patients. The vaccine administration begins at the end of the RT-CT (Induction Phase) and is subsequently al-ternated with TMZ cycles (Maintenance Phase). The primary endpoints are PFS and safety. Among the secondary endpoints, are the in vitro and in vivo Immune response evaluations. Results By December 2022 , nine patients had been enrolled in the first step. Two patients progressed within three months after leukapheresis and none had experienced DC vaccine-related G3-4 tox-icity. Five patients had a positive DTH test against KLH. By June 2023. The median OS from leu-kapheresis was 23.1 months and 24.7 from surgery. Conclusions This combination therapy is well-tolerated, and we have achieved the two endpoints required for the first step. Therefore, the study will proceed to enroll the remaining 19 patients.

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

Researchers and organizations are pursing 100 Day Vaccine Development to reduce the impact of any new pandemic-causing virus. They propose monitoring viral emergence and developing vaccines for discovered viruses which would undergo safety testing in humans. If one of these viruses emerges, phase III trials would then take place. There are two problems with this approach - first, phase III trials are too long for the 100-day goal and second, the virus that emerged might not have been discovered in their surveillance. An alternative approach would be to first develop vaccines for viral families similar to the pan coronavirus vaccines being proposed for next generation COVID vaccines. Phase III trials for them would be run even if a virus in the family wasn’t having an outbreak. If a virus in a family for which a vaccine has been developed has an outbreak and the phase III trialed vaccine is not effective against it, develop a booster based on the phase III trialed vaccine. Since booster development and approval takes less than 100 days, the 100 Day Vaccine Development goal would be met.

Dengue is a pan-tropical arthropod-borne disease, endemic in over 100 countries. The dengue virus comprises four antigenic serotypes (DENV 1-4). The envelope (E) and non-structural 1 (NS1) proteins are highly immunogenic, and the E protein carries epitopes eliciting neutralizing antibodies. In previous studies, mice immunizations with two DNA vaccines encoding the E ectodomain (pE1D2) and NS1 proteins (pcTPANS1) from DENV2 induced high protection. Based on these findings, we constructed new plasmids containing the codon-optimized genes from these proteins for expression in mouse and human cells, named pEotmD2 and pNS1otmD2. Compared to the pE1D2, the pEotmD2 mediated lower expression of the recombinant protein in human and mouse cell lines, while the pNS1otmD2 plasmid was slightly more efficient than the pcTPANS1 in these cells. Immunogenicity and protection were evaluated in BALB/c mice immunized with the original and codon-optimized plasmids followed by challenged with DENV2. In accordance with the in vitro experiments, the antibody response and protection elicited by the pE1otmD2 plasmid was lower than those observed with the pE1D2. In contrast, the pNS1otmD2 vaccine enabled slightly higher levels of the humoral and protective responses than the pcTPANS1. Overall, our study revealed different effects of codon optimization on these two dengue DNA vaccines.

The recent introduction of foot-and-mouth disease virus serotype O (O/EA-2 topotype) in Southern Africa region has changed virus dynamics and the FMD vaccine requirements. This study describes an assessment of the heterologous antibody responses induced by O Manisa vaccine (three PD50/dose) against a representative O/EA-2 virus collected from an FMD outbreak in Zambia. Commercial and subsistence cattle herds were monitored following vaccination, where the benefits of employing a double vaccination schedule were compared to single-dose vaccination. Testing using virus neutralisation showed cattle that received two vaccine doses had a mean reciprocal log virus neutralisation titre of 2.02 (standard error [SE] = 0.16, n = 9) for commercial herds and 1.65 (SE = 0.17, n = 5) for subsistence herds , 56 days after first vaccination (dpv). Significantly lower mean titres were observed for single-dosed commercial herds (0.90, SE = 0.08, n = 9) and subsistence herds (1.15, SE = 0.18, n = 3), 56 dpv. Comparison of these results and those generated by solid-phase competitive ELISA by cohen’s kappa coefficient observed a statistically significant (ρ = 0.598 for 1:10 dilution, and ρ = 0.562 for 1:30 dilution of SPCE % inhibition results, p &lt; 0.001 for both dilutions) positive correlation.

As of the end of 2022, despite the disruptions caused by the COVID-19 pandemic, the global HIV epidemic persists, with 39 million individuals living with the virus and 1.3 million new infections reported in that year. Opportunistic infections associated with AIDS claimed the lives of over 630,000 people in 2022, contributing to a cumulative death toll exceeding 40.4 million since the disease's emergence in 1981. Although advances in HIV diagnosis and antiretroviral therapy have transformed the disease into a manageable chronic condition, issues like drug resistance, low compliance, and high treatment costs persist. Until a vaccine becomes available, a comprehensive approach involving prevention and therapy is essential, particularly for high-risk populations. Research shows that prevention strategies are more cost-effective than treatment. The development of antiretroviral drugs has also spurred the creation of antivirals for other infections. The emergence of COVID-19 vaccines has opened new avenues for HIV vaccine development, as lessons from vaccine platform technologies like mRNA, viral vectors, and protein subunits can be applied to HIV. This review explores the most promising prophylactic and therapeutic HIV vaccine trials, emphasizing the need for a multi-pronged approach combining vaccines with non-vaccine strategies. Though significant progress is anticipated, the road to a viable HIV vaccine remains long, especially for high-risk populations, such as medical workers, blood transfusion recipients, and drug users. The combinatorial approach, capitalizing on various aspects of immunity, may hold the key to defeating HIV in the future.

Background Healthcare workers (HCWs) have suffered considerable morbidity and mortality during the COVID-19 pandemic. Few data on COVID-19 vaccine effectiveness (VE) are available from middle-income countries in Europe. We evaluated primary series COVID-19 VE against laboratory-confirmed COVID-19 among HCWs in Georgia. Methods HCWs in six hospitals in Georgia were invited to enroll in a prospective cohort study conducted during March 19–December 5, 2021. Participants completed weekly symptom questionnaires. Symptomatic HCWs were tested by RT-PCR and/or rapid antigen test (RAT), and participants were routinely tested for SARS-CoV-2 by RT-PCR or RAT, regardless of symptoms. Serology was collected at enrolment, and quarterly thereafter, and tested by electrochemiluminescence immunoassay for SARS-CoV-2 antibodies. We defined primary series vaccination as two doses of COVID-19 vaccine received ≥14 days before symptom onset. We estimated VE as (1-hazard ratio)*100 using a Cox proportional hazards model with vaccination status as a time-varying covariate. Estimates were adjusted by potential confounders that changed the VE estimate by more than 5%, according to the change-in-estimate approach. Results Overall, 1561/3849 (41%) eligible HCWs enrolled and were included in the analysis. The median age was 40 (IQR: 30-53), 1318 (84%) were female, and 1003 (64%) had laboratory evidence of prior SARS-Cov-2 infection. At enrolment, 1300 (83%) were unvaccinated; By study end, 1082 (62%) had completed a primary vaccine series (69% BNT162b2 (Pfizer-BioNTech); 22% BBIBP-CorV (Sinopharm); 9% other). During the study period, 191(12%) participants had a new PCR- or RAT-confirmed symptomatic SARS-CoV-2 infection. VEa gainst PCR- or RAT- confirmed symptomatic SARS-CoV-2 infection was 58 (95%CI: 41; 70) for all primary series vaccinations, 68% (95%CI: 51; 79) for BNT162b2, and 40% (95%CI: 1; 64) for BBIBP-CorV vaccines. Among previously infected HCWs, VE was 58% (95%CI: 11; 80). VE against medically attended COVID-19 was 52% (95%CI: 28; 68), and VE against hospitalization was 69% (95% CI: 36; 85). During the period of predominant Delta variant circulation (July-December 2021), VE against symptomatic COVID-19 was 52% (95%CI: 30; 66). Conclusions Primary series vaccination with BNT162b2 and BBIBP-CorV was effective at preventing COVID-19 among HCWs, most of whom had previous infection, during a period of mainly Delta circulation. Our results support the utility of COVID-19 primary vaccine series, and the importance of increasing coverage, even among previously infected individuals.

The analysis reported here is unique in that it is the first study of the original data from the Pfizer/BioNTech BNT162b2 mRNA vaccine clinical trial (CA4591001) to be carried out by a group unaffiliated with the trial sponsor. Our study is a forensic analysis of the 38 trial subjects who died between July 27, 2020, the start of Phase 2/3 of the clinical trial, and March 13, 2021, the data end date of their 6-Month Interim Report. Phase 2/3 of the trial involved 44,060 subjects who were equally distributed into two groups and received Dose 1 of either the BNT162b2 mRNA vaccinated or the Placebo control (0.9% normal saline). At Week 20, when the BNT162b2 mRNA vaccine received Emergency Use Authorization from the U.S. FDA, subjects in the placebo arm were given the option to be BNT162b2 vaccinated. All but a few accepted. Surprisingly, a comparison of the number of subject deaths per week during the 33 Weeks of this study found no significant difference between the number of deaths in the vaccinated versus placebo arms for the first 20 weeks of the trial, the placebo-controlled portion of the trial. After Week 20, as subjects in the Placebo were unblinded and vaccinated, deaths among this still unvaccinated cohort of this group slowed and eventually plateaued. Deaths in the BNT162b2 vaccinated subjects continued at the same rate. Our analysis revealed inconsistencies between the subject data listed in the 6-Month Interim Report and publications authored by Pfizer/BioNTech trial site administrators. Most importantly, we found evidence of an over 3.7-fold increase in number of deaths due to cardiovascular events in BNT162b2 vaccinated subjects compared to Placebo controls. This significant adverse event signal was not reported by Pfizer/BioNTech. Potential sources of these data inconsistencies are identified.

Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differentiation difficult, and while treatment is largely similar between vaccine injury and long covid, there are important distinctions. Furthermore, diagnostics are important for monitoring treatment progress and assessing the extent of subclinical vaccine injury in population having received a covid-19 vaccine. The development of rigorous diagnostics is an important step towards the recognition of both long covid and vaccine injury, as those suffering these conditions have faced immense challenges in having their conditions recognized, treated, and compensated by insurance companies or national health services.

Background: To our knowledge, the sudden onset of symptomatic pulmonary hypertension after COVID-19 vaccination has not been described. Both cases presented here resulted in functional limitations and likely permanent organ damage. Case Summary: We report two cases of acute onset pulmonary hypertension in previously healthy adult males within three weeks of receiving the second dose of the Pfizer (BNT162b2) mRNA COVID-19 vaccine from different lots. Both patients experienced the sudden onset of severe fatigue and dyspnea on exertion with negative COVID-19 PCR testing. The diagnosis was made by serial transthoracic echocardiography in the first case and by both transthoracic echocardiography and right heart catheterization in the second. Discussion: Pulmonary hypertension is a serious disease characterized by damage to lung vasculature and restricted blood flow through narrowed arteries from the right to left heart. The onset of symptoms is typically insidious, progressive and incurable, leading to right heart failure and premature death. The World Health Organization (WHO) classifies pulmonary hypertension into 5 categories and recently re-defined as a resting mean pulmonary artery pressure greater than 20 mmHg. Sudden onset pulmonary hypertension would only be expected in the settings of surgical pneumonectomy or massive pulmonary emboli with compromise of at least 50% of the lung vasculature.

Traditional vaccines are produced by using weakened or inactivated forms of disease-causing pathogens to produce the target antigen they are designed to protect against. Messenger RNA vaccines are a class of vaccines that employ a minute segment of genetic material, known as messenger RNA (mRNA), which contains directives for the cells in the body to generate a particular protein. This genetic material is synthesized in the laboratory and packaged into a lipid nanoparticle, which protects and helps it enter cells for further protein synthesis. During vaccination with mRNA vaccine, the lipid nanoparticles containing the mRNA are injected into the muscle of vaccinees. Once inside the cells, the mRNA instructs the cells to produce a protein which is then displayed on the surface of the cell, triggering an immune response. During this, the immune system recognizes the displayed protein as foreign and mounts a defense by producing antibodies and activating immune cells to target and eliminate the protein. Furthermore, these immune responses generate a memory cell, facilitating the immune system to promptly react in case of encountering the authentic pathogen as an infection in the future. The mRNA vaccines are flexible and the sequence can be easily synthesized in the lab based on the genetic information of the target pathogen. Additionally, mRNA vaccines can be developed for new strains or variants of the target disease easily. This was particularly evident during the COVID-19 pandemic, where mRNA vaccines like the Pfizer-BioNTech and Moderna vaccines were developed and authorized for emergency use within a year. But currently, available mRNA vaccines require extensive cold chain, antigen delivery, potential immune response variability optimization, and sophisticated manufacturing process. The efforts to explore next-generation mRNA vaccine development are aimed to further improve the effectiveness, stability, and delivery methods. One focus of research has been to enhance the stability of mRNA vaccines, particularly temperature sensitivity which makes storage and distribution easier, particularly in regions with limited access to cold chain infrastructure. Self-amplifying mRNA vaccines, on the other hand, are designed to generate multiple copies of the mRNA within cells which potentially leads to a higher production of the target protein, resulting in a stronger immune response. Additionally, studies are exploring new delivery systems to improve the target and efficiency of mRNA vaccines using specialized nanoparticles and liposomes to specifically deliver mRNA to certain cell types or immune cells. Another area of interest is the development of combination vaccines, where multiple mRNA sequences are included in a single vaccine protecting against multiple diseases targeting strains or variants of a particular pathogen simultaneously. While current mRNA vaccines are administered via intramuscular injection, studies are underway to deliver directly into the skin offering enhanced immune response and the ability to use smaller vaccine doses.

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

Vaccine hesitancy remains a public health challenge. It has been argued that the sources of vaccine-related information may serve as important condiments to one’s decision to be vaccinated. However, little empirical attention is given to the subject. We contribute to this debate by assessing the level of COVID-19 vaccine hesitancy and the role of information explaining hesitancy, using the Nelson Mandela Bay Municipality of South Africa as a case study. Findings confirm high level of vaccine hesitancy, representing 78.8 percent of the respondents (which is above the national level of 41%). Furthermore, findings reveal that vaccination decisions are influenced by family, which is the most trusted among all institutions in the society, especially on sensitive matters and those shrouded by myths and misinformation. Additionally, the majority trusts health care workers and mass media as sources of health-related and general information; however, the use of popular personalities to convey health information is not supported. The findings reveal key socio-demographic and institutional drivers of COVD-9 vaccine hesitancy, such as age, inadequate information on the vaccine, trust issues, conspiracy beliefs, vaccine-related factors, and perceived side effects associated with the vaccine. Recommendations based on the findings are provided.

The phenomenon of vaccine hesitancy is a growing threat to public health with far-reaching implications. The widening gap between the vaccinated and the proportion needed for herd immunity raises two critical research questions that are of interest to practitioners, researchers, and policymakers: (1) What determines one’s decision to be vaccinated? and (2) What is the implication of COVID-19 vaccine hesitancy on economic recovery? In this study, we use empirical data in the context of South Africa to investigate factors affecting COVID-19 vaccine hesitancy and their implications for economic recovery. Findings reveal key socio-demographic and institutional drivers of COVD-9 vaccine hesitancy, which include age (the youth are more hesitant), inadequate information on the vaccine (those who perceive they have adequate information are vaccinated), trust issues in government institutions, conspiracy beliefs, vaccine-related factors, and perceived side effects associated with the vaccine. Additionally, an individual’s decision to remain hesitant about COVID-19 vaccination has implications for businesses and the economy by limiting movement and trade, increasing unemployment, and causing a resurgence of new variants. Based on the findings, action plans such as information dissemination, convenience vaccination centers, consistency communications, and targeted campaign strategies are recommended for improving vaccine intakes and a positive economic recovery.

Introduction. Covid-19 faced the world with serious health and socioeconomic issues. At the very beginning of the pandemics, the vaccine was considered by health authorities and the medical community the only way to curb the spread of the virus. One of the measures that have been proposed to increase vaccinations was the mandatory policy. The purpose of this study was to compare determinants of voluntary and mandatory vaccination among students of Albanian University. Methodology: This cross-sectional study by means of an online survey, was conducted among students enrolled in the private University “Albanian University”, Tirana, Albania during the last week of winter semester 7-14 Feb 2022. Results: 878 students participated in this study, among them 612 (69.7%) were females, 266 (30%) were males. 506 (57%) of the participants were enrolled in Medical Sciences (MS), 372(42.3%) were Non-Medical Science (Non-MS) group. 773 (88%) was vaccinated against Covid-19, 105 (11.8%) were not vaccinated. 466 (53%) reported voluntary vaccination, 412 (46.9%) reported mandatory vaccination. Among students that vaccinated voluntary 266 (57%) were from MS group, 200(42.9%) from Non-MS group. 237(57.5%) of students in mandatory vaccination group were from MS group, 175 (42.4%) from Non-MS. Conlusion. Vaccine safety and efficacy were hindering factors of vaccination. Also, based on the results of this study, the students felt encouraged to vaccinate by the academic staff. This clearly demonstrates that the staff does not lack the skills to enhance stu-dents' knowledge about the risk of infectious diseases and the importance of vaccination. Therefore, to influence as much as possible students’ attitude toward vaccination, comprehensive educational programs including modification of existing curricula should be considered.

Background Several vaccines have been approved for prevention of the coronavirus disease discovered on 31st December in Wuhan, China. Pakistan procured vaccines from various countries. However, the lack of knowledge and reluctance of the general population to embrace the use of the vaccines are considered to be the major determinants of the slow vaccination rate. Hence, it is necessary to evaluate the willingness of the general population about their perception of the COVID-19 vaccination. Methods A cross sectional survey based on a self-structured questionnaire comprising 18 questions was conducted (from April 21-June 21) on 400 Pakistani participants to evaluate their knowledge, attitude and perception towards the COVID-19 vaccination. Chi-square independent t-test and one-way Anova including a multiple step wise linear regression were used to draw conclusions about the results. P< 0.05 was considered significant. Results A total of 400 participants responded in the KAP survey of which 46.5% were female and 53.5% were male. The mean age of participants was 36.08 years. This survey showed a poor knowledge (50.5%), a fair attitude (75.1%) and a poor perception (58.1%) towards the COVID-19 vaccination. Higher mean knowledge and attitude scores was reported in the age group 21-40, females and unmarried urban citizens. Regression analysis showed that age, education, residence and employment status influenced the knowledge and perception score to a considerable extent. Conclusions The findings reflect an inadequate knowledge and perception on the one hand but a better attitude towards the COVID-19 vaccination. This KAP survey will help in better understanding the opinion of the general population towards vaccination and will be useful for policy makers and health care authorities aiming to increase the vaccination rate.

Rabies is a life-threatening and vaccine-preventable infectious disease and is triggered by an RNA virus, part of the Rhabdoviridae family, Lyssavirus genus. It is transmitted from infected saliva due to biting, but also from contact with infected blood or organs from rabid animals to humans. Children are at high risk due to their inability to defend themselves from infected animals and most deaths occur with a particularly high incidence in this category (under the age of 15 years). Postexposure prophylaxis (PEP) is standard and life-saving if given early after exposure. We are reporting the case of a ten-year-old female child, who was bitten by an unvaccinated cat ten days before admission to the Paediatric Intensive Care Unit at National Institute for Infectious Diseases „Prof. Dr Matei Bals”, Bucharest. The child had category III cat bites and did not receive PEP. Suggestive clinical manifestations such as an altered general state, psychomotor agitation, auditory and visual hallucinations, and hypersomnia followed by aerophobia and hydrophobia were present. Despite the maximal treatment introduced from early admission (Human Rabies Immunoglobulin, anti-rabies vaccination, orotracheal intubation plus mechanical ventilation, vital functions’ support, parenteral feeding, symptomatic drugs) the evolution of the patient was unfavourable, namely death two months after admission. The diagnosis was established in both pre-mortem by identifying the rabies virus in the cerebrospinal fluid based on reverse transcription-polymerase chain reaction (RT-PCR) and post-mortem by a histopathological examination (which reveals the presence of Babes-Negri bodies in the hippocampus). The objective is to understand the mechanism of infection and mortality from rabies virus in children. Conclusion: The most effective prevention methods are early administration of specific prophylaxis (immunoglobulin and vaccination) and, most importantly, early elimination of animal rabies outbreaks, while rapid diagnosis is helpful in the management of human rabies in humans. The rate of human exposure may be significantly decreased by controlling rabies through pet immunization programs.

Background: This study describes the attitudes and practices of Brazilian adults regarding the mandatory vaccination for COVID-19 and the hesitancy to children´s vaccination. Methods: The participants answered an online questionnaire disseminated on social networks. An adaptation of the SAGE-WG questionnaire was used to measure the children's vaccination hesitancy. Results: Among 1,007 participants, 677 (67.4%) believed that vaccination for COVID-19 among adults should be mandatory. Just over half of the participants (51.5%) believe that parents and guardians should be free to decide whether their children should be vaccinated against COVID-19, and 9.1% were unsure about this. Younger, non-religious people who have higher self-perceptions of risk for COVID-19, and who evaluate the federal government's performance in combating the disease as bad or very bad, have a higher agreement with mandatory vaccination, a lower agreement that parents and guardians should be free to vaccinate their children, and lower child vaccination hesitancy scores. Conclusion: In Brazil, mandatory COVID-19 vaccination for adults is far from a consensus, and an expressive part of the population believes that parents and guardians should be free to choose whether or not to vaccinate their children. These perceptions and vaccine hesitancy for children are associated with religious and political inclinations.

Introduction: Studies conducted in real-life scenarios on vaccine protection against COVID-19 constitute an important global priority, but one that is currently mostly neglected in low- and middle-income countries such as Angola. Here, we analyze for the first-time vaccine protection against COVID-19 in a real-life scenario after 6 months of implementing a multi-vaccination plan in Angola, providing estimation of odds ratios in vaccinated individuals and vaccine efficacy against infection by SARS-CoV-2 in a period that coincided with the identification of the Omicron variant in the country. Methods: We used a negative test case-control design to assess the effectiveness of vaccination against confirmed SARS-CoV-2 infection. A total of 4.232 vaccinated and unvaccinated individuals with the result of a rapid antigen diagnostic test against SARS-CoV-2 performed from December 27 to 28, 2021 were included in the study. Data were extracted from the Digital Vaccination Record Platform (Rediv) of the Ministry of Health of Angola. All ethical procedures related to the authorization necessary to carry out the study were followed. Statistical analyzes were performed using version 7.5.2.0 of CDC's Epi Info. Frequency distributions and measures of central tendency were used to characterize the study universe. The general and sex-adjusted and age-adjusted odds ratios, were evaluated by comparing the chances of vaccination between cases and controls, and their associated 95% CI, which were calculated using the Mantel-Haenszel stratification method. The risk classification of Axel Kroeger, Piscoya and Alarcon was used to interpret the odds ratio. The Breslow-Day statistic was used to assess the homogeneity of the odds ratios. Vaccine efficacy was calculated using the odds ratio applying the accepted statistical vaccine efficacy formula:(1 − odds ratio) × 100. For all estimates, a P value < 0.05 was considered statistically significant. Results: The population consisted of 63.63% male and 36.37% female. The mean age was 36 years with a standard deviation of 13. 83. Regarding vaccination status, 83.27% of individuals were vaccinated and 16.73% were unvaccinated, with 21.81% positive and 78.19% negative for SARS -CoV-2. The odds of SARS-CoV-2 infection were 0.85 (95% CI 0.70 – 1.03) times lower in vaccinated compared to unvaccinated individuals, with P=0.09. The overall vaccine efficacy (VE) was 15% (95% CI -3 – 30). Conclusion: There was no statistically significant decrease in the chances of SARS-CoV-2 infection in vaccinated versus unvaccinated individuals. However, the overall vaccine efficacy was 15%.

We determined the levels of neutralizing antibodies against the SARS-CoV-2 ancestral strain, Delta and Omicron variants of concern (VOCs) in 125 healthcare workers, who received Coro-naVac as their primary vaccination and later received either a single ChAdOx1 or a combination of two consecutive boosters using either two ChAdOx1 doses or a ChAdOx1 or BNT162b2 as the primary and second boosters, respectively, or 2 doses of BNT162b2. The titers 12 weeks after primary vaccination were inadequate to neutralize the all strains. After a single ChAdOx1 boost-er, the levels of neutralization at Day 30 varied significantly, only a small proportion of partici-pants developing neutralizing titers against Omicron at Day 7 and 30. The two doses of ChA-dOx1 as the booster induced lowest activity. A combination ChAdOx1 and BNT162b2 induced greater neutralization than by two doses of ChAdOx1. Two doses of BNT162b2 as the booster had the maximal activity against Omicron VOC.

The 10-valent pneumococcal vaccine was introduced in Pakistan’s Expanded Program on Immunization (EPI) in 2013 as a 3+0 schedule without catchup. We conducted three annual cross-sectional surveys from 2014-2016 to measure vaccine-type (VT) carriage in infants from a rural part of Pakistan. Nasopharyngeal specimens were collected by random sampling of infants from 2 union councils of Matiari. Samples were then transported to Infectious Disease Research Laboratory (IDRL) at the Aga Khan University within 6-8 hours of collection. Serotypes were established using sequential multiplex PCR. Of the 665 children enrolled across three surveys, 547 were culture positive for pneumococcus. VT carriage decreased from 21·8% in 2014 to 12·7% in 2016 (p-value for trend <0·001). Those who were not vaccinated or partially vaccinated were found to be at higher risk of carrying a VT serotype (aOR 2·53, 95% CI 1·39, 4·63 for non-vaccinated) and (aOR 3·35, 95% CI 1·82, 6·16 for partially vaccinated). On the other hand, being enrolled in the most recent survey was negatively associated with VT-carriage (aOR 0·51, 95% CI 0·28, 0·93). We found that PCV10 was effective in decreasing the carriage of vaccine-type serotypes in Pakistani infants.

The COVID-19 pandemic has highlighted the adverse consequences created by an infodemic specifically on compliance with public health guidance and vaccine uptake. COVID-19 vaccine hesitancy is a complex construct that is related to health beliefs, misinformation exposure, and perceptions of governmental institutions. This study draws on theoretical models and current data on the COVID-19 infodemic to explore the association between perceived risk of COVID-19, levels of misinformation endorsement, and opinions about the government response on vaccine uptake. We surveyed a sample of 2,697 respondents from the US, Canada, and Italy using a mobile platform between 21-28 May, 2021. Using multivariate regression, we found that country of residence, risk perception of contracting and spreading COVID-19, perception of government response and transparency, and misinformation endorsement was associated with the odds of vaccine hesitancy. Higher perceived risk was associated with lower odds of hesitancy, while lower perceptions of government response, and higher misinformation endorsement were associated with higher hesitancy.

The novel coronavirus disease (COVID-19) has created immense threats to public health on various levels around the globe. The unpredictable outbreak of this disease and the pandemic situation are causing severe depression, anxiety and other mental as physical health related problems among the human beings. To combat against this disease, vaccination is essential as it will boost the immune system of human beings while being in the contact with the infected people. The vaccination process is thus necessary to confront the outbreak of COVID-19. This deadly disease has put social, economic condition of the entire world into an enormous challenge. The worldwide vaccination progress should be tracked to identify how fast the entire economic as well as social life will be stabilized. The monitor ofthe vaccination progress, a machine learning based Regressor model is approached in this study. This tracking process has been applied on the data starting from 14^th December, 2020 to 24^th April, 2021. A couple of ensemble based machine learning Regressor models such as Random Forest, Extra Trees, Gradient Boosting, AdaBoost and Extreme Gradient Boosting are implemented and their predictive performance are compared. The comparative study reveals that the AdaBoostRegressor outperforms with minimized mean absolute error (MAE) of 9.968 and root mean squared error (RMSE) of 11.133.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated influenza virus vaccines (LAIVs) are thought to induce both humoral and cellular immune responses by mimicking a natural infection, but their effectiveness have recently come into question. Thus, the opportunity exists to find alternative approaches to improve overall influenza vaccine effectiveness. Two alternative IBV backbones were developed with re-arranged genomes, re-arranged M (FluB-RAM) and a re-arranged NS (FluB-RANS). Both re-arranged viruses showed temperature sensitivity in vitro compared to the WT type B/Bris strain, were genetically stable over multiple passages in embryonated chicken eggs and were attenuated in vivo in mice. In a prime-boost regime in naïve mice, both re-arranged viruses induced antibodies against HA with hemagglutination inhibition titers considered of protective value. In addition, antibodies against NA and NP were readily detected with potential protective value. Upon lethal IBV challenge, mice previously vaccinated with either FluB-RAM or FluB-RANS were completely protected against clinical disease and mortality. In conclusion, genome re-arrangement renders efficacious LAIV candidates to protect mice against IBV.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) infects dromedary camels and zoonotically infects humans, causing a respiratory disease with severe pneumonia and death. With no approved antiviral or vaccine interventions for MERS, vaccines are being developed for camels to prevent virus transmission into humans. We have previously developed a chimpanzee adenoviral vector-based vaccine for MERS-CoV (ChAdOx1 MERS) and reported its strong humoral immunogenicity in dromedary camels. Here, we looked back at total RNA isolated from three immunised dromedaries pre and post-vaccination during the first day; and performed RNA sequencing and bioinformatic analysis in order to shed light on the molecular immune responses following a ChAdOx1 MERS vaccination. Our finding shows that a number of transcripts were differentially regulated as an effect of the vaccination, including genes that are involved in innate and adaptive immunity, such as type I and II interferon responses. The camel Bcl-3 and Bcl-6 transcripts were significantly upregulated, indicating a strong activation of Tfh cells, B cell, and NF-kB pathways. In conclusion, this study gives an overall view of the first changes in the immune transcriptome of dromedaries after vaccination; it supports the potency of ChAdOx1 MERS as a potential camel vaccine to block transmission and prevent new human cases and outbreaks.

Sexually transmitted infections (STIs) such as Gonorrhea is associated with serious morbidity and mortality rates in the world considering the multiple virulence factors possessed. The disease is manifested as salpingitis, pelvic inflammatory disease (PID), and bacteremia and is controlled by macrophages, dendritic cells, neutrophils, T cells, epithelial cells and cytokines. Dihydroliponamide acetyltransferase, a component of the mitochondrial pyruvate complex can be used as immunogenic target. Recent changes in the strain allowed the bacteria to acquire resistance against antibiotics.Vaccination remains an alternative to prevention against the disease. This study predicts an effective epitope-based vaccine against dihydrolipoamide acetyltransferase of Neisseria Gonorrhea using immunoinformatics approaches. Sequences retrieved from NCBI were passed on several prediction tests to analyze for possible B-cell, T-cell MHC class I epitopes and class II. Two epitopes showed high binding affinity for B-cells, while thirteen epitopes showed high binding affinity for MHCI and forty-five for MHCII. A population coverage of 100% for combined MHC I and II dictates the huge number of individuals who will benefit from formulating the vaccine. We recommend invivo and invitro studies to prove our prediction results.

This review will explore the four major pillars required for design and development of an saRNA vaccine: antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). In will report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects.

Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.

Dengue virus (DENV), the causative agent of dengue fever (DF), is one of the most important mosquito-borne viruses that can infect humans. Although much effort has been made on prevention and control of dengue, there are currently no anti-viral drugs or worldwide approved vaccines yet. In this study, we immunized six-week-old Balb/c mice with DNA vaccine candidates E and NS1-2a of DENV serotype 2 or the combination of them (E+NS1-2a) via an electroporation (EP)-assisted intramuscular gene delivery system and evaluated the immune response and protection. The highest specific antibody titres and cytokine levels secreted by splenocytes as well as the highest survival rate were observed in the E+NS1-2a group, followed by E group and NS1-2a group. Our data suggested that the combination of E and NS1-2a delivered by EP may be a superior preventive strategy against DENV.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

To develop a modern plague vaccine, we used hypo-endotoxic Yersinia pestis bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. Similar holin-endolysin system from phage λ containing mutated holin gene S and intact genes R-Rz coding for the endolysins caused generation of mixtures of BGs that had (i) practically preserved and (ii) completely lost their original rigidity. The addition of protein E to the work of this system shifted the equilibrium in the mixture towards the collapsed sacs. The collapse of the structure of BGs can be explained by endolysis of peptidoglycan sacculi. Immunizations of laboratory animals with the variants of BGs followed by infection with a wild-type Y. pestis strain showed that bacterial envelopes protected only cavies. BGs with peptidoglycan maximally hydrolyzed had a greater protectivity compared to BGs with preserved peptidoglycan skeleton.

Treatment of osteochondritis dissecans of the knee, has always been a challenge for orthopedic surgeons. We present a case report of a 38-year-old male with severe right knee pain after suffering from an indirect trauma and axial rotation of the knee, limiting knee functionality and impeding ability to walk, with diagnosis of osteochondritis dissecans in the trochlea of the knee, who underwent arthroscopic treatment with matrix induced autologous chondrocyte implantation (MACI). After the surgery, physical therapy protocol for MACI was implemented, magnetic imagen resonance images with cartilage mapping were used to evaluate recovery of the lesion. A total recovery was observed evaluated with the modified Cincinnati knee rating system (mCKRS). A discussion is provided with evidence and general recommendations for the use of MACI in the treatment of adult OCD of the knee.

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.

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.

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.

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.

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.

Modern engineering faces challenges in ensuring technical standards for service, durability, and sustainability. Political, administrative, and budgetary factors, coupled with climate change, pose tasks to structural integrity, affecting industries and economies. Marine infrastructures represent a strategic asset of the country as it handles a large part of the economic exchanges. This article analyzes five essential factors that play a fundamental role in the performance analysis of coastal structures: Chloride-induced corrosion, degradation models, maintenance strategies, monitoring, and climate change. Starting with reinforcement corrosion, considered as the main cause of distress, particularly in coastal zones for the long-term behavior of structures. Additional pressure from the influences of climate change is becoming evident and extreme, leading to reduction in capacity. To guarantee the lifespan, degradation models contribute by estimating the long-term performance of the asset as a strategic piece to the development of effective maintenance solutions. Additionally, quantifying the condition of the structure from monitoring data, plays a crucial part that provides information on the current situation of the structure. Finally, this review summarizes the challenges associated with the maintenance of aging marine structures considering aspects such as corrosion, monitoring, and the future challenges this area will face due to climate change.

2,4-dichlorophenoxyacetic acid (2,4-D) is a globally used herbicide and is frequently found in water samples. This fact has prompted studies on its effects in non-target organisms, revealing significant alterations on liver structure and function. In this review, we evaluated the literature on the hepatotoxicity of 2,4-D, focusing on morphological damages, biomarkers of toxicity and affected liver functions. Searches were conducted on PubMed, Web of Science and Scopus and 83 articles were selected after curation. Among the studies, 72% used in vivo models and 30% used in vitro models. Additionally, 48% used the active ingredient, and 35% used commercial formu-lations in exposure experiments. The most affected biomarkers were related to a decrease in an-tioxidant capacity, including alterations in the activities of catalase and superoxide dismutase, and in the levels of malondialdehyde. Changes in energy metabolism, lipids, liver function, and xenobiotic metabolism were also identified. Furthermore, we found studies about the effects of 2,4-D in mixtures with other pesticides, as well as hepatoprotection trials. The reviewed data in-dicate that the reduction in antioxidant capacity and oxidative stress play an important role in 2,4-D-induced hepatotoxicity. However, the mechanism of action of the herbicide is still not ful-ly understood and further research in this area is needed.

Photodynamic therapy (PDT) has garnered significant attention in the fields of cancer treatment and drug-resistant bacteria eradication due to its non-invasive nature and spatiotemporal controllability. Iridium complexes have captivated researchers owing to their tunable structure, exceptional optical properties, and substantial Stokes displacement. However, most of these complexes suffer from aggregation-induced quenching, leading to diminished luminous efficiency. In contrast to conventional photosensitizers, photosensitizers exhibiting aggregation-induced luminescence (AIE) properties retain the ability to generate a large number of reactive oxygen species when aggregated. To overcome these limitations, we designed and synthesized a novel iridium complex named Ir-TPA in this study. It incorporates quinoline triphenylamine cyclomethylated ligands that confer AIE characteristics for Ir-TPA. We systematically investigated the photophysical properties, AIE behavior, spectral features, and reactive oxygen generation capacity of Ir-TPA. The results demonstrate that Ir-TPA exhibits excellent optical properties with pronounced AIE phenomenon and robust capability for producing singlet oxygen species. This work not only introduces a new class of metal iridium complex photosensitizer with AIE attributes but also holds promise for achieving remarkable photodynamic therapeutic effects in future cellular experiments and biological studies.

Transit-oriented development (TOD), such as metro depot and over-track building complexes, has expanded rapidly in China. Over-track building construction has the advantage of comprehensive utilization of land resources, ease of commuting to work, and provide funds for subway construction. However, there still has a pending problem, disturbance of railway vibration, for TOD. Excessive noise and vibration seriously affect people’s life. To address this challenge, field measurements are used to obtain the vibration source characteristics and vibration propagation of the ground and the superstructure in this study. And the typical metro depot with over-track building in Wuhan was selected. The effects of vibration on the surrounding ground and adjacent buildings caused by the operation of trains have been measured, and the propagation law of train-induced ground vibration acceleration in the time and frequency domains has been analyzed. The distribution and propagation laws of vibration noise, structural noise and secondary structure noise in sensitive areas such as the throat area, depot area, test section and access section of the over-track buildings and their impact laws on the over-track buildings are obtained. And the effectiveness of the vibration and noise reduction methods used were evaluated. Results show that within 43 m from the train running track, the train running induced vertical vibration acceleration level in the high-rise building peak size of 58.8 dB, the average value of 55.62 dB; vibration frequency components are mainly 40-60 Hz. The findings might provide useful insight for designing vibration mitigation systems in new metro depots with over-track buildings.

Target pests of genetically engineered crops producing both defensive allelochemicals and Bacillus thuringiensis (Bt) toxins often sequentially or simultaneously uptake allelochemicals, Bt toxins, and/or insecticides. How the three types of toxins interact to kill pests remains underexplored. Here we investigated the interactions of Bt toxin Vip3A, plant allelochemical flavone, and insecticide emamectin benzoate in Spodoptera frugiperda. Simultaneous administration of flavone LC25 + Vip3A LC25, emamectin benzoate LC25 + Vip3A LC25, and flavone LC15 + emamectin benzoate LC15 + Vip3A LC15 but not flavone LC25 + emamectin LC25 yielded a mortality significantly higher than their expected additive mortality (EAM). One-day preexposure to one toxin at LC5 followed by 6-day exposure to the same toxin at LC5 plus another toxin at LC50 showed that the mortality of flavone LC5 + Vip3A LC50, emamectin benzoate LC5 + Vip3A LC50, and Vip3A LC5 + emamectin benzoate LC50, were significantly higher than their EAM, while that of flavone LC5 + emamectin benzoate LC50 was significantly lower than their EAM. No significant difference existed among the mortalities of Vip3A LC5 + flavone LC50, emamectin benzoate LC5 + flavone LC50, and their EAMs. The results suggest that the interactions of the three toxins are largely synergistic (inductive) or additive, depending on their combinations and doses.

This paper deals with the quantitative analysis of measured fracture-induced electromagnetic radiation (FEMR) in the vicinity of the Dead Sea Transform using the Angel-M1 instrument, which enables the recording of FEMR signals in a 3D manner. Results show both the possibility of estimating the sizes of micro-fractures that are the sources of the radiation, and of assessing the direction of their location to the measuring device and the range of magnitude Mw of the impending "events" (EQ's) associated with the present FEMR measurements. Moreover, the relation between the measured FEMR activity (the number of FEMR hits per unit time) and the FEMR event magnitudes shows consistency with the Gutenberg-Richter relationship for the region. Such measurements could therefore constitute a preliminary 'field reinforcement' towards an EMR valid method for a real earthquake forecast, which would provide much earlier warnings than the seismic ones. Obviously, the present observed FEMR measurements can only be used as an assessment of the stress concentration and micro-fracturing in the region since they relate to the very initial nucleation phase of a "virtual" (extremely low Richter scale value) earthquake, but they do provide the necessary feasibility test for a prediction method since all lab-measured FEMR features were confirmed also in the field.

Cotton (Gossypium spp.) is a major source of natural fiber and an important cash crop. The cotton growth habit and architecture determine its productivity and influence management strategies for commercial production. The GATA transcription factors (TFs) control various developmental processes in plants, such as flower, bract and embryo development, and petal differentiation. As stable transformation is still a bottleneck in many plant species, TRV-VIGS was used to manipulate gene expression in different plants, including Gossypium hirsutum L. In this study, we undertook the TRV-based VIGS to functionally characterize two candidate genes, Gohir.D05G103700 and Gohir.D12G153600, identified through the expression QTL analysis for five floral induction and meristem identity genes using the upland cotton mini-core collection. Virus-induced silencing of the Gohir.D05G103700 gene resulted in up to a 1.4-fold reduction in the transcript level in two inoculated plants, G3 and G4, and Gohir.D12G153600 gene resulted in up to a 2.3-fold reduction in transcript level in a single inoculated plant P05 relative to the mock-treated plant. The TRV2-Gohir.D05G103700 inoculated plants precisely G3 and G4 also exhibited loss of the supernumerary (fourth) floral bract in the squares, whereas the TRV2-Gohir.D12G153600 inoculated plants did not show any observable phenotypic change relative to the mock-treated plants.  Altogether, this study suggested that TRV-VIGS can be used to characterize genes in cotton relatively rapidly and the cotton Gohir.D05G103700 gene is a positive regulator of the indeterminate growth habit in cotton, which could be manipulated to obtain a cotton plant with architecture best suited for the cultivation area.

Heavy metal contamination is listed among the most alarming threats to the environment and human health. The detrimental effects of heavy metals in the natural environment span from a reduction of biodiversity to toxic effects on marine life - through microplastic born heavy metals -, to impairment of microbial activity in the soil, and to detrimental effects on animal reproduction. A host of different chemical and biological technologies have been proposed to alleviate environmental contamination by heavy metals. Relatively less attention has been paid to the microbial precipitation of heavy metals, as a side mechanism of the most general process of microbially induced calcite precipitation (MICP). This process is currently receiving a great deal of interest from both a theoretical and practical standpoint, because of its possible practical applications in concrete healing and soil consolidation, and its importance in the more general framework of microbial induced mineral precipitation. In this study, we analyse the ability of the marine bacteria Vibrio harveyi in co-precipitating CaCO3 minerals, together with Cd, Cr, Pb, and Zn added in form of nitrates, from solutions containing CaCl2. The precipitated carbonatic minerals were a function of the different heavy metals present in the solution. The process of co-precipitation appears to be rather effective and fast, as the concentrations of the 4 heavy metals were reduced in 2 days by 97.2%, on average, in the solutions.

A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article's main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a promising approach but remains a challenging technology of regenerative medicine for damaged myocardium. Efforts have been focused on improving the efficiency by understanding fundamental mechanisms. One of the major challenges is that the plasticity of cultured fibroblast varies batch to batch with unknown mechanisms. Here, we noticed that a portion of in vitro cultured fibroblasts have been activated to differentiate into myofibroblasts, marked by the expression of αSMA, even in the primary cell culture of tissues. Both forskolin, which activates adenylyl cyclase and increases cAMP concentration, and TGFbeta inhibitor SB431542 can efficiently suppress myofibroblast differentiation of cultured fibroblasts. However, SB431542 improved but forskolin blocked iCM reprogramming of fibroblasts that were infected with retroviruses of Gata4, Mef2c and Tbx5 (GMT). Moreover, inhibitors of cAMP downstream signaling pathways, PKA or CREB-CBP, significantly improved the efficiency of iCM reprogramming. Consistently, inhibition of p38/MAPK, another upstream regulator of CREB-CBP, also improved reprogramming efficiency. We then investigated if inhibition of these signaling pathways in primary cultured fibroblast could improve their plasticity for reprogramming, and found that preconditioning of cultured fibroblasts with CREB-CBP inhibitor significantly improved the cellular plasticity of fibroblasts to be reprogrammed, yielding ~2-fold amount of reprogrammed iCMs compared to that of untreated control cells. In conclusion, suppression of cAMP/PKA/CREB signaling axis improves fibroblast plasticity for direct cardiac reprogramming.