Porcine epidemic diarrhea (PED) is a swine wasting disease caused by coronavirus infection. It causes great economic damage to the swine industry worldwide. Despite the continued use of vaccines, PED outbreaks continue, highlighting the need to review the effectiveness of current vaccines and develop additional vaccines based on new platforms. Here, we review existing vaccine technologies for preventing PED and highlight promising technologies that may help control PED virus in the future.

Porcine epidemic diarrhea virus (PEDV) causes severe enteric disease in pigs, particularly neonatal piglets. Attempts to develop a safe and effective vaccine have been unsuccessful. Ginseng stem-leaf saponins (GSLS), a promising oral adjuvant candidate, can improve intestinal immune responses in poultry and mice. However, the low stability limits the further use. Poly lactic-co-glycolic acid (PLGA), a biocompatible and biodegradable nanoparticle, have been widely used in biomedicine for stable and targeted drug delivery. In this study, we developed GSLS-PLGA nanoparticles (GSLS-NPs) and evaluated the mucosal adjuvant efficacy in vitro and in vivo. GSLS-NPs significantly enhanced antigen internalization and pro-inflammatory cytokine secretion by DC2.4 cells. Mice orally administered GSLS-NPs before intramuscular inoculation generated CD11b+CD8α- and CD11b-CD103+ dendritic cells in the spleen and draining mesenteric lymph nodes, respectively, which are the types mainly responsible for antigen presentation. Additionally, enhanced neutralizing and non-neutralizing antibody responses and expanded activities of specific effector and memory CD4+ and CD8+ T cells were also observed in mice immunized with PEDV vaccines plus GSLS-NPs compared to mice receiving the vaccines alone. Furthermore, GSLS-NPs showed a good safety profile and presented great advantages over GSLS aqueous solution. Collectively, our results highlight the potential of GSLS-NPs as a mucosal adjuvant and provide an attractive vaccination strategy for combatting PEDV. Further study is required to evaluate the efficacy of this mucosal adjuvant in swine.

Base on the sequence of S genes, which encode spike proteins, we previously identified three different types (North American, S INDEL and S large-DEL types) of porcine epidemic diarrhea virus (PEDV) that have re-emerged in Japan since 2013. Base on experimental infections with the North American and S large-DEL types, we also hypothesized that PEDV virulence may be linked to the S1 subunit of the S protein. To test this hypothesis, we have now assayed in gnotobiotic piglets various recombinant PEDVs generated by reverse genetics. Piglets inoculated with CV777 maintained in National Institute of Animal Health, along with piglets infected with a recombinant form of the same virus, developed subclinical to mild diarrhea. In contrast, severe watery diarrhea, dehydration, weight loss, astasia, and high mortality were observed in piglets inoculated with recombinant strains in which the S gene was partially or fully replaced with corresponding sequences from the highly virulent Japanese PEDV isolate OKN-1/JPN/2013. Indeed, symptoms resembled those in piglets inoculated with the OKN-1/JPN/2013, and were especially pronounced in younger piglets. Collectively, the data demonstrate that the S1 subunit of the S protein is an important determinant of PEDV virulence, and advance development of new vaccine candidate.

Porcine epidemic diarrhea virus (PEDV) has affected the pork industry worldwide and during outbreaks the mortality of piglets has reached 100%. Lipid nanocarriers are commonly used in the development of immunostimulatory particles due to their biocompatibility and slow-release delivery properties. In this study, we developed a lipid nanoparticle (LNP) complex based on glycyrrhizinic acid (GA) and tested its efficacy as an adjuvant in mice immunized with the recombinant N-terminal domain (NTD) of porcine epidemic diarrhea virus (PEDV) spike (S) protein (rNTD-S). The dispersion stability analysis (Z-potential–27.6 mV) confirmed the size and charge stability of the LNP-GA, demonstrating that the particles were homogeneously dispersed and strongly anionic, that favors nanoparticles binding with the rNTD-S protein, which showed a slightly positive charge (2.11 mV) by in silico analysis. TEM image of LNP-GA revealed nanostructures with a spherical-bilayer lipid vesicle (⁓100 nm). The immunogenicity of the LNP-GA-rNTD-S complex induced an efficient humoral response 14 days after the first immunization (P < 0.05) as well as an influence on the cellular immune response by decreasing serum TNF-α and IL-1β concentrations, which was associated with an anti-inflammatory effect.

Porcine epidemic diarrhea virus (PEDV) has caused great damage to the global pig industry. The innate immunity plays a significant role in resisting viral infection, however, the exact role of innate immunity in the anti-PEDV response has not been fully elucidated. In this study, we observed that various porcine innate immune signaling adaptors are involved in the anti-PEDV activity. Among these, TRIF and MAVS showed the strongest anti-PEDV activity. The endogenous TRIF, MAVS and STING were selected for further examination of anti-PEDV activity. Agonist stimulation experiments showed that TRIF, MAVS and STING signaling all have obvious anti-PEDV activity. The siRNA knockdown assay showed that TRIF, MAVS and STING are also all involved in anti-PEDV response, and their remarkable effects on PEDV replication were confirmed in TRIF-/-, MAVS-/- and STING-/- Vero cells. For further verification, the anti-PEDV activity of TRIF, MAVS and STING could be reproduced in porcine IPEC-DQ cells. In summary, this study reveals that multiple pattern recognition receptor (PRR) signaling pathways of porcine innate immunity play an important role in the anti-PEDV infection, providing new and useful antiviral knowledge for prevention and control of PEDV spreading.

The epidemiological patterns of Bovine Viral Diarrhea (BVD) in North Africa and Mediterranean Basin (MB) are endemic with highly socio-economic impacts. The objective of the study was conducted to investigate the level of sero-prevalence of BVDV in Libya and the associated risk factor. A total of 1599 serum samples were collected from herds of cattle which belonging to seven Libyan regions. All sera were assayed by using screening ELISA assay for detection of antibodies against BVDV. An overall seroprevalence of BVDV was estimated to be 48.6% (95% CI, 46.08%-50.98%). Considering the age group, a seroprevalence of 36.8% was detected in cattle <1 year, 41.0% in cattle between 1 and 2 years of age and 48.6% in cattle aged more than 2 years. Statistically significant differences (p<0.001) between age groups were reported. Seroprevalence of BVDV was significantly associated with geographical region (P=0.033). This is the first study on BVD in Libya and the results of this study would suggest that BVD is endemic in Libya.

The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3’mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased and improved SwIV replication, in co-infected NPTr and iPAM 3D4/21 cells respectively, compared to single infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell type-dependent-manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

The objective of this study was to evaluate the potential benefits of feeding spray-dried porcine plasma (SDPP) to pigs infected with African swine fever virus (ASFV). Two groups of twelve weaned pigs each were fed with CONVENTIONAL or 8% SDPP enriched diets. Two pigs (trojans)/group) were injected intramuscularly with the pandemic ASFV (Georgia 2007/01) and comingled with the rest of the pigs (1:5 trojan:naïve ratio) to simulate a natural route of transmission. Trojans developed ASF and died within the first week after inoculation but contact pigs did not develop ASF, viremia or seroconversion. Therefore, three more trojans per group were introduced to optimize the ASFV transmission (1:2 trojan:naïve ratio). Blood, nasal and rectal swabs were weekly harvested and at end of the study, ASFV-target organs collected. After the second exposure, rectal temperature of conventionally fed contact pigs increased >40.5˚C while fever was delayed in the SDPP contact pigs. Additionally, PCR Ct values in blood, secretions and tissue samples were significantly lower (P<0.05) for CONVENTIONAL compared to SDPP contact pigs. Under these study conditions, contact exposed pigs fed SDPP had delayed ASFV transmission and reduced virus load, likely by enhanced specific T-cell priming after the first ASFV-exposure.

Diarrhea and fever are prevalent childhood illnesses with potentially severe consequences, especially when they co-occur. This study investigates the prevalence and determinants of diarrhea, fever, and their coexistence among children under-five in Bangladesh. Data from the 2017-18 Bangladesh Demography and Health Survey (BDHS) were analyzed using multivariable stepwise logistic regression with backward selection. This study found that 5.0% for diarrhea, 34.0% for fever, and 3.0% for the coexistence of both illnesses. Common factors associated with childhood diarrhea and fever included the mother's education, her attitude toward wife-beating, and the child’s age (12-23 months). Diarrhea was associated with households with improved water sources and children in the Barisal division, while fever was linked to underweight children and those from more affluent backgrounds. The coexistence of both was significantly linked to underweight children, higher birth orders, and children from the Rajshahi division. Notably, child illnesses were associated with parental education, higher socio-economic status, and access to improved drinking water sources. Diarrhea affects one in 20 children, fever affects one in three, and the coexistence of both conditions affects one in 35 children in Bangladesh. The findings need further research and policy reviews to develop effective interventions and improve child health in Bangladesh.

In this paper, by using the variational method, a sufficient condition for the unique existence of the stationary solution of the reaction-diffusion ecosystem is obtained, which directly leads to the global asymptotic stability of the unique equilibrium point. Moreover, delayed feedback ecosystem with reaction-diffusion item is considered, and utilizing impulse control results in the globally exponential stability criterion of the delayed ecosystem. It is worth mentioning that the Neumann zero-boundary value that the infected and the susceptible people or animals should be controlled in the epidemic prevention area and not allowed to cross the border, which is a good simulation of the actual situation of epidemic prevention. And numerical examples illuminate the effectiveness of impulse control, which has a certain enlightening effect on the actual epidemic prevention work . That is, in the face of the epidemic situation, taking a certain frequency of positive and effective epidemic prevention measures is conducive to the stability and control of the epidemic situation. Particularly, the newly-obtained theorems quantifies this feasible step. Besides, utilizing Laplacian semigroup derives the $p$th moment stability criterion for the impulsive ecosystem.

Abstract. Marek's disease virus is an oncogenic avian herpesvirus and the problem of oncogenicity of this virus for humans remains unexplored. This pathology appeared in broiler chickens of 30 days and older, that is from now on the contact with poultry meat carries the risk of infecting people. This article analyzes the risks of the emergence of the epidemic potential of the Marek's disease virus in the Russian Federation taking into account the characteristics of modern pig and poultry farming. It was found that COVID 19 can serve as an additional factor in reducing the resistance of the population to herpesvirus infections. The COVID 19 epidemic is accompanied by folic acid deficiency which also increases the risk of contamination of diseases associated with DNA viruses, including an extended risk of animal viruse infection. Since, according to our estimates, Marek's disease occurred in at least 25% of broiler poultry farms in the Russian Federation, a possible expand in mortality from neoplasms of the reproductive system for the Russian Federation as a whole can contribute to the dynamics of oncological diseases of reproductive organs and breast cancer. Since 2011 a contagious form of intestinal pathology, vesicular enteritis, has widely spread at poultry farms in the Russian Federation. During periods of extending incidence of vesicular enteritis, we recorded cases of inflammation of the facial nerves and subfebrile temperature in contact persons, bursts of oncological diseases in veterinary personnel (ovarian cancer, breast cancer), abnormal and synchronous increases in the incidence of infectious larengotracheitis and Marek's disease in chickens under the age of 40 days which requires additional monitoring studies.

Molecular mechanisms associated with the pathogenesis of Vesicular stomatitis virus (VSV) in livestock remain poorly understood. Several studies have highlighted the relevant role of macrophages in controlling the systemic dissemination of VSV during infection in different animal models, including mice, cattle and pigs. To gain more insight on the molecular mechanisms used by VSV to impair the immune response in macrophages, we used microarrays to determine the transcriptomic changes produced by VSV infection in primary cultures of porcine macrophages. The results indicated that VSV infection induced the massive expression of multiple anorexic, pyrogenic, proinflammatory and immunosuppressive genes. Overall, the interferon (IFN) response appeared suppressed, leading to the absence of stimulation of interferon-stimulated genes (ISG). Interestingly, VSV infection promoted the expression of several genes known to downregulate the expression of IFNb. This represents an alternate mechanism for VSV control of the IFN response, beyond the recognized mechanisms mediated by the matrix protein. Although there was no significant differential gene expression in macrophages infected with a highly virulent epidemic strain compared to a less virulent endemic strain, the endemic strain consistently induced higher expression of all upregulated cytokines and chemokines. Collectively, this study provides novel insights into VSV molecular pathogenesis and immune evasion that warrants further investigation

Porcine reproductive and respiratory syndrome virus (PRRSV) infections cause significant economic losses to swine producers every year. Aerosols containing infectious PRRSV are an important route of transmission, and proper treatment of air could mitigate the airborne spread of the virus within and between barns. Previous bioaerosol studies focused on the microbiology of PRRSV aerosols; thus, the current study addressed the engineering aspects of virus aerosolization and collection. Specific objectives were to (1) build and test a virus aerosolization system, (2) achieve a uniform and repeatable aerosol generation and collection throughout all replicates, (3) identify and minimize sources of variation, (4) verify that the collection system (impingers) performed similarly. The system for virus aerosolization was built and tested (Obj. 1). The uniform airflow distribution was confirmed using a physical tracer (<12% relative standard deviation) for all treatments and sound engineering control of flow rates (Obj. 2). Theoretical uncertainty analyses and mass balance calculations showed <3% loss of air mass flow rate between the inlet and outlet (Obj. 3). A comparison of TCID₅₀ values among impinger fluids showed no statistical difference between any two of the three trials (p-value = 0.148, 0.357, 0.846) (Obj. 4). These results showed that the readiness of the system for research on virus aerosolization and treatment (e.g., by ultraviolet light), as well as its potential use for research on other types of airborne pathogens and their mitigation on a laboratory scale.

The rapid spread of African swine fever virus (ASFV), causing severe and often lethal disease in domestic pigs and Eurasian wild boar, continues to be a threat for pig populations and dependent industries. Despite scientific achievements that deepen our understanding of ASFV pathogenesis, alternative transmission routes for ASFV remain to be elucidated. We previously demonstrated the efficient transmission of ASFV from infected boars to naïve recipient gilts via artificial insemination, thereby highlighting the importance of surveillance in boar semen prior to shipment. Since accurate and reliable detection of even low amounts of ASFV in boar semen is key for disease prevention and control, we established a suitable diagnostic pipeline to efficiently detect ASFV genome in boar semen. Here, we assessed sensitivity, specificity and overall performance of various routine nucleic acid extraction kits as well as qPCR protocols in detecting ASFV genome in blood and semen of boars. Feasibility of respective kits and methods for future use in boar studs was also considered. Variability in sensitivity mostly concerned samples with low to very low amounts of ASFV genome. Ultimately, we defined a well-suited pipeline to precisely detect ASFV genome in boar semen, as early as 2 days post ASFV infection.

We analyze the humoral and B-cell mediated immunogenic response induced by GP5 lineal epitopes from porcine reproductive and respiratory syndrome virus (PRRSV) to explore the role of this protein in the protective response. For inoculation, pigs aged twenty-one days were allocated into six groups (seven pigs per group): control (PBS), vehicle (carrier), vaccinated (Ingelvac-PRRSV, MLV®), non-vaccinated and naturally infected, GP5-B and GP5-B3. Subsequently blood samples were collected and analyzed. Cytokine were measured by ProcartaPlex kit. Peptide-specific IgGs and cross-reactivity against peptides were analyzed by ELISA and B-cell subpopulations were analyzed by flow cytometry. At 2 days post-immunization (dpi), the GP5-B3 peptide increased the serum concentrations of cytokines associated to activate adaptive cellular immunity (IL-1β and IL-12). The concentration of IgGs anti-GP5-B increased in both cases at 21 and 42 dpi, while IgGs anti-GP5-B3 increased at 21 dpi and remained at the same level until 42 dpi. Also, antibody-forming/Plasma B cells (CD2+/CD21-) and primed B cells (CD2-/CD21+) from immunized pigs showed an increase at 42 dpi. Conversely the naïve B cells from immunized pigs decreased compared with the controls. Importantly, Both GP5-B and GP5-B3 peptides exhibited immunoreactivity against serum antibodies from vaccinated group, as well as non-vaccinated and naturally infected group. In conclusion, GP5-B and GP5-B3 peptides elicited immunogenicity mediated by antigen specific IgG´s and B-cell activation.

Rapid proliferation of traditional gold mining sites in Kédougou a Southeast region in Senegal, led to mass population migration from the neighboring West African countries and rapid expansion of small mining villages with poor hygiene and sanitation conditions. An outbreak of hepatitis E was reported in 2014 with several cases of febrile jaundice among traditional mine workers. In this study, we analyzed both HEV IgM and IgG seroprevalence and the associated risk factors of infection by testing any suspected case and contacts collected from February 2012 to November 2014. RNA-negative sera from suspected cases and contacts were tested for anti-HEV IgM and anti-HEV IgG. A total of 799 sera were collected from 290 suspected cases, 470 contacts and 39 individuals with missing information. The median age of the cohort study was 19 years (1-88 years) with a male/female sex-ratio of 1.9. We found an overall prevalence of 43.68% (332/760) of anti-HEV IgM and 38.15% (290/760) of anti-HEV IgG sera. Our data provide new insights into the HEV epidemiology and point to the crucial need to estimate the disease’s burden in Kédougou and assess the viral mechanisms driving the disease’s severity in pregnant women.

Porcine parvovirus (PPV) 1 is a major causative pathogen of reproductive failure, and porcine circovirus (PCV) 2 is an etiological pathogen causing PCV-associated and PCV diseases worldwide. PPV2–6 and PCV3 were recently identified as newly emerging viruses with unknown pathogeneses. However, little is known of PPV1–6 and PCV3 effects or their co-infections with PCV2. In this study, we examined 926 samples (272 aborted pig fetuses and 654 pig lung tissues) from domestic pig farms for the presence of PPV1–6 or PCV3 and for PCV2 co-infection with these seven viruses. The prevalence of PPV and PCV was significantly greater in lung tissue samples than aborted pig fetus samples. PPV3–6 were detected for the first time in Korean domestic pigs. Co-infection rates with PCV2 and other viruses were significantly higher in abattoir samples than that in aborted pig fetus samples. Concurrent infections are more common than single infection in pig population and nu-merous infectious pathogens such as PPV and PCV2 can impact the respiratory diseases. Fur-thermore, Korean PPV1 strain (PPV1-82) was identical to the virulent PPV-27a strain in this respect. Our results describe, for the first time the prevalence of PPV1–6 and PCV3 infections and their co-infection rates with PCV2 in Korean domestic pigs.

Respiratory tract epithelium infection plays a primary role in Nipah virus (NiV) pathogenesis and transmission. Knowledge about infection dynamics and host responses to NiV infection in respir-atory tract epithelia is scarce. Studies in non-differentiated primary respiratory tract cells or cell lines indicate insufficient interferon (IFN) responses. However, studies are lacking to determin-ing complex host response patterns in differentiated respiratory tract epithelia to understand NiV replication and spread in swine. Here we characterized infection and spread of NiV in differenti-ated primary porcine bronchial epithelial cells (PBEC) cultivated at the air-liquid-interface (ALI). After the initial infection of only a few apical cells, lateral spread for 12 days with epithelium disruption was observed without releasing substantial amounts of infectious virus from the api-cal or basal sides. Deep time course proteomics revealed pronounced upregulation of genes re-lated to type I/II- IFN, immunoproteasomal subunits, TAP-mediated peptide transport and MHC I antigen presentation. Spliceosomal factors were downregulated. We propose a model in which NiV replication in PBEC is slowed by a potent and broad type I/II-IFN host response with con-version from 26S proteasomes to immunoproteasomal antigen processing and improved MHC I presentation for adaptive immunity priming. NiV induced cytopathic effects could reflect the focal release of cell-associated NiV, which may contribute to efficient airborne viral spread between pigs.

Rotavirus species H (RVH) has been detected in pigs, humans and bats. Moreover, porcine RVHs have been recently identified in several swine-producing countries. Despite their zoonotic impact, genome information of RVHs is still limited. This study aimed to establish a tentative complete genome-based genotyping system for RVHs, by appending genomic sequences from 12 porcine RVHs identified in Japan between 2013 and 2015 to those from human and other porcine RVHs reported in previous studies. Phylogenetic analysis of 11 RNA segments indicated that porcine RVHs could be classified into multiple genotypes. Consequently, the genotype classification for RVHs revealed the existence of genotypes 10G, 6P, 6I, 3R, 4C, 7M, 6A, 2N, 4T, 6E, 3H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Surprisingly, two distinctive types in NSP1 and NSP3 genes were identified from among the twelve porcine RVHs. Our data suggest a potentially novel gene rearrangement event between porcine RVH and rotavirus species C in the NSP3 gene. These findings would provide a new insight in understanding for evolution of RV.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide, accounting for approximately 25% of deaths among pregnant women. We previously reported that pregnancy serum facilitates HEV replication in vitro. However, the differences in host cells with HEV infection induced by pregnancy serum and fetal bovine serum (FBS) are unclear. In this study, differentially expressed proteins were identified in HEV-infected hepatoma cells (HepG2) supplemented with different sera by using isobaric tags for relative and absolute quantitation. Proteomic analysis indicated that HEV infection significantly induced 1014 differentially expressed proteins in HEV-infected HepG2 cells when supplemented with FBS compared with pregnancy serum. Further validation by Western blot confirmed that filamin A, heat-shock proteins 70 and 90, Cytochrome c, and Thioredoxin were associated with HEV infection. This comparative analysis provides an important basis to further investigate HEV pathogenesis in pregnant women and HEV replication.

Misinformation during the COVID-19 outbreak has shaped our perception of the disease. Some people thinkthe disease is a bioweapon while others are convinced that it is a hoax. Heightened anxiety often producesfearful rumors, some of which are absurd while others seem plausible and are laced with some truths. But, how does misinformation affect disease spread? In this paper, we construct a mathematical model parameterized by Ugandan data, to study the effect of misinformation on community COVID-19 spread. The analysis shows that misinformation leads to high number of COVID-19 cases in a community, and the effect is highest in the rumour initiators and spreaders. This analysis underscores the importance of addressing misinformation in COVID risk communication.

In the promptness of the COVID-19 outbreak, it would be very important to observe and estimate the pattern of diseases to reduce the contagious infection. To study this effect, we developed a COVID-19 analytical epidemic framework that combines with isolation and lockdown effect by incorporating five various groups of individuals. Then we analyze the model by evaluating the equilibrium points and analyzing their stability as well as determining the basic reproduction number. The extensive numerical simulations show the dynamics of a different group of the population over time. Thus, our findings based on the sensitivity analysis and the reproduction number highlight the role of outbreak of the virus that can be useful to avoid a massive collapse in Bangladesh and rest of the world. The outcome of this study concludes that outbreak will be in control which ensures the social and economic stability.

Thirty-six healthy 21-day-old weaned ternary piglets (Duroc × Landrace × Yorkshire) were randomly divided into 2 treatments with 18 replicates per treatment and 1 pig per replicate. The control group was fed with basal diet and the test group was fed with diets supplemented with 1 kg/t tea residue. The test period was 28 days. The results are as follows: The addition of tea residue in the diet has no significant effect on the growth performance of weaned piglets (P > 0.05), but it could significantly reduce the diarrhea rate of piglets from 1 to 7 days and 1 to 28 days (P < 0.05). Compared with the control group, the dietary supplementation of tea residue had no significant effect on nutrient apparent digestibility, plasma biochemical indexes and plasma immune indexes (P > 0.05), but increased the content of glutathione in plasma (P < 0.05). Tea residue had no significant effect on the morphology of jejunum and ileum of piglets (P > 0.05), but it could significantly reduce the content of chloride ion in feces (P < 0.05). Compared with the basal diet group, there was no significant difference in the relative expression of TMEM16A and CFTR mRNA in the colon of weaned piglets (P > 0.05). The whole-cell patch clamp recording showed that the TMEM16A and CFTR ion channels could be activated by ionomycin and forskolin, respectively. However, when the HT-29 cells transfected with TMEM16A and CFTR channels were treated with tea residue extract, it could significantly inhibit the chloride current of the TMEM16A and CFTR ion channels (P < 0.05).

This review highlights the potential and limitations of mRNA vaccines with a particular focus on mucosal delivery as an alternative to parenteral administration. The strengths of mRNA vaccines are: a) Versatility: they can be adapted to target a wide range of pathogens; b) Faster development: designed and produced more quickly than traditional vaccines; c) High efficacy: effective in preventing severe disease, as demonstrated during the COVID-19 pandemic. Current challenges: a) Delivery: current methods (mainly intramuscular injection) may not be optimal for inducing mucosal immunity; b) Stability: mRNA is fragile and needs to be protected from degradation; c) Safety: potential side effects, including myocarditis, blood clotting, allergic reactions need further investigation. Mucosal delivery could be more effective in preventing the transmission of pathogens and is generally better accepted by the population. Pros: offers the potential to induce local immunity at the site of pathogen entry, potentially providing broader protection; Cons: developing effective delivery systems and adjuvants for mucosal delivery is difficult. Extracellular vesicles as a mucosal delivery system are promising and offer a potentially safe, scalable, and needle-free approach. Future directions: a) Optimizing mRNA constructs: strategies like codon optimization and self-amplifying RNA can improve stability and translation efficiency; b) Rigorous pre-clinical studies are essential before human trials.

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

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

With the rapid evolution of SARS-CoV-2, the emergence of new strains is an intriguing question. This paper presents an evolutionary theory to analyze the mutations of the virus and identify the conditions that lead to the generation of new strains. We represent the virus variants using a 4-letter sequence based on amino acid mutations on the spike protein and employ an n-distance algorithm to derive a variant phylogenetic tree. We show that the theoretically-derived tree aligns with experimental data on virus evolution. Additionally, we propose an A-X model, utilizing the set of existing mutation sites (A) and a set of randomly generated sites (X), to calculate the emergence of new strains. Our findings demonstrate that a sufficient number of random iterations can predict the generation of new macro-lineages when the number of sites in X is large enough. These results provide a crucial theoretical basis for understanding the evolution of SARS-CoV-2.

Campylobacter is one of the most commonly reported foodborne bacteria worldwide. Although C. jejuni and C. coli have been reported to be responsible for the great majority of campylobacterio-sis, the burden of infections by species other than C. jejuni and C. coli have been increasing as a result of a transition to diagnostic test methods that enable the isolation of emerging species. The aim of the present study was to recover C. jejuni, C. coli, and emerging species from the stool samples of 500 patients with gastroenteritis and 100 healthy subjects by use of a filtration meth-od and culture techniques using Butzler agar and mCCDA under microaerophilic or hydrogen enriched atmosphere, identify the species by multiplex PCR methods and assess the significance of emerging species in enteric diseases. Thirty-one (6.2%) Campylobacter spp. were isolated from the stool samples of diarrheic patients but none from healthy individuals. Of 31 isolates, 21 (67.8%), 9 (29%) and 1 (3.2%) were identified as C. jejuni, C. coli and C. concisus by multiplex PCR, respectively. Filtration method was superior to the culture technique using mCCDA under mi-croaerophilic atmosphere. C. concisus was evaluated as the etiology of gastroenteritis as a result of laboratory and clinical evaluations. The present study was the first to indicate that emerging Campylobacter species are rarely detected and C. concisus is linked to acute gastroenteritis in Tur-key where additional studies are warranted to clarify the significance of emerging species in gastroenteritis.

(1) Background:The objective of this study was to explorethe dynamic changes of gut microbiota in Simmental calves before weaning, and compared microbial composition and functionality differences between diarrhea and health calves; (2) Methods: Fourteen neonatal Simmental calves were divided into a health group (n = 8) and diarrhea group (n = 6). The rectal stool samples were collected from each calf on days 1, 3, 5, 7, 9, 12, 15, 18, 22, 26, 30, 35, and 40. The high-throughput sequencing analysis of the 16S rRNA gene V1–V9 region was conducted to explore the changes in gut microbiota over time in both groups and assess the influence of diarrhea on microbiota structure and function; (3) Results: E.coli, B.fragilis, and B.vulgatus were the top three bacterial species of pre-weaning Simmental calves.Meanwhile, the major functions of fecalmicrobiota included the “Metabolic pathways”,“Biosynthesis of secondary metabolites”,“Biosynthesis of antibiotics”, “Microbial metabolism in diverse environments”, and “Biosynthesis of amino acids”. For calves in health group, PCoA revealed that the bacterial profiles generated from days 1, 3, 5, 7, and 9 separated from days 15, 18, 22, 26, 30, 35, and 40. While the microbial profiles of calves on day 12 crossed with both clusters, suggesting that the dynamic changes of microbial structures with the increasing of ages. When compared the difference of the relative abundance of bacteria between calves in health and diarrhea groups, the results showed that the relative abundance of the beneficial L.johnsonii, F.prausnitzii, and Limosilactobacillus in the health group were significantly higher than those in the diarrhea group (p

In March 2013, a novel avian influenza A H7N9 virus was emerged in China, which cause rapidly progressive pneumonia and with a high fatality rate. Serologic studies to evaluate neutralizing antibodies of infected patients and birds are invaluable tools for immunogenicity research of H7N9 and epidemiological investigation. Conventional neutralization assays are laborious and time-consuming which also hampered by biosafety requirement. In this study, We construct and produce pseudovirus bearing the full-length hemagglutinin (HA) of H7N9 virus in the Env-defective, luciferase-expressing HIV-1 backbone. The production of lentiviral pseudovirus was analysed by HA gene specific real-time reverse-transcription PCR, transmission electron microscopy (TEM), and Western Blot assay to prove the nucleic acid replication, the morphology of virus, and the expression of HA protein in pseudovirus. After that pseudovirus based inhibition assay was established to detect neutralizing antibodies of a panel of serum samples. Our results demonstrated that H7N9 pseudovirus which had single-cycle infection was generated. By comparing the neutralization antibody titers, pseudovirus based neutralization test could be recognized as an alternative of conventional microneutralization (MN). Hence, we conclude that it is possible to use pseudovirus inhibition assay to screen sera samples, as well as evaluate vaccine-induced neutralizing antibodies against H7N9 virus.

The ongoing COVID-19 pandemic has raised numerous questions concerning the shape and range of state interventions whose goals are to reduce the number of infections and deaths. The lockdowns, which have become the most popular response worldwide, are assessed as being an outdated and economically inefficient way to fight the disease. However, in the absence of efficient cures and vaccines, there is a lack of viable alternatives. In this paper we assess the economic consequences of the epidemic prevention and control schemes that were introduced in order to respond to the COVID-19 pandemic. The analyses report the results of epidemic simulations that were obtained using the agent-based modelling methods under the different response schemes and their use in order to provide conditional forecasts of the standard economic variables. The forecasts were obtained using the DSGE model with the labour market component.

Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.

(1) Background: Group A rotaviruses (RVAs) are the primary cause of severe intestinal diseases in piglets. Porcine rotaviruses (PoRVs) are widely prevalent in Chinese farms, resulting in significant economic losses to the livestock industry. However, isolation of PoRVs is challenging, and their pathogenicity in piglets is not well understood. (2) Methods: We conduct clinical testing on a farm in Jiangsu Province, China, and isolate strains of porcine rotavirus by continuously passaging on MA104 cells. Subsequently, the pathogenicity of the isolated strain in piglets was investigated.The piglets of the PoRV-infection group were orally inoculated with 1 mL of 1.0 × 10⁶ TCID50 PoRV, whereas those of the mock-infection group were fed with an equivalent amount of DMEM. (3) Results: Fecal samples were collected from 28 piglets, all of which tested positive for RVAs. A G5P[23] genotype porcine rotavirus strain was successfully isolated from one of the positive samples and named RVA/Pig/China/JS/2023/G5P[23](JS). The genomic constellation of this strain was G5-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Sequence analysis revealed that the genes VP3, VP7, NSP2, and NSP4 of the JS strain were closely related to human RVAs, whereas the remaining gene segments were closely related to porcine RVAs, indicating a reassortment between porcine and human strains. Furthermore, infection of 15-day-old piglets with the JS strain resulted in a diarrheal rate of 100% (8 of 8) and mortality rate of 37.5% (3 of 8).(4) Conclusion: The isolated G5P [23] genotype rotavirus strain, which exhibited strong pathogenicity in piglets, may have resulted from recombination between porcine and human strains. It may serve as a potential candidate strain for developing vaccines, and its immunogenicity can be tested in future studies.

The expression microarray technique was performed to investigate the differences in gene expression between Czech Large White pigs and wild boars in the longissimus lumborum et thoracis and biceps femoris muscle tissues. The NREP gene (neuronal regeneration related protein homolog) was selected for detailed study as an expressional and functional candidate gene. NREP plays a role in the transformation of neural, muscle and fibroblast cells and in smooth muscle myogenesis. Quantitative real-time PCR results confirmed that the porcine NREP gene was expressed in both skeletal muscles and significantly overexpressed in Czech Large White pigs compared to wild boars (P &lt; 0.05). We identified 9 polymorphic sites in genomic DNA of NREP gene. Six of these polymorphisms were in complete linkage disequilibrium and therefore only 4 polymorphisms were informative. Associations of these 4 polymorphisms (HF571253:g.103G&gt;A, HF571253:g.134G&gt;A, HF571253:g.179T&gt;C and HF571253:g.402_409delT) with meat performance traits were assessed in Czech Large White pigs. New polymorphisms in NREP gene were significantly associated with parameters of daily weight gain, lean meat and backfat thickness in Czech Large White pigs. Our primary study suggested that porcine NREP may play an important role in skeletal muscle growth, fat metabolism and meat performance traits.

Purpose: To investigate the extent of anterior chamber angle circumference needed to maintain a physiological outflow facility (C). Methods: Twenty anterior segments of porcine eyes were assigned to 5 groups, each with a different degree of cyanoacrylate-mediated angle closure: 90° (n = 4), 180° (n = 4), 270° (n = 4), 360° (n = 4) and four unoccluded control eyes. The outflow facility was measured at baseline, 3, 12, 24, and 36 hours after angle closure. Outflow patterns were evaluated with canalograms and the histomorphology was compared. Results: Baseline outflow facilities of the five groups were similar (F = 0.922, P = 0.477). Complete, circumferential occlusion over 360° induced a significant decrease in facility from baseline at all time-points (P ≤ 0.023 at 3, 12, 24 and 36 hours). However, no difference from baseline was found in any of the partially-occluded (0–270°) groups (F ≥ 0.067, P ≥ 0.296 at 3, 12, 24 and 36 hours). The canalograms confirmed the extent of occlusion with flow through the unblocked regions. Histology revealed no adverse effects of blockage on the TM or aqueous plexus in the unoccluded angle portions. The unoccluded TM appeared normal. Conclusion: Cyanoacrylate-mediated angle occlusion created a reproducible angle closure model. 90° of unoccluded anterior chamber angle circumference was sufficient to maintain physiological outflow. This model may help understand how outflow can be regulated in healthy, nonglaucomatous TM.

In the context of the COVID-19 epidemic, and on the basis of the Theory of Dynamical Systems, we propose a simple model for the expansion of contagious diseases, with a particular focus on viral respiratory tracts. The infection develops through contacts between contagious and exposed people, with a rate proportional to contact duration and turnover, inversely proportional to the efficiency of protection measures, and balanced by the average immunological response. The obvious initial exponential increase is readily hindered by the size reduction of the exposed population. The system converges towards a stable attractor whose value is expressed in terms of the ratio C/D of contamination vs decay factors. Decreasing this ratio below a critical value leads to a tipping point beyond which the epidemic is over. By contrast, significant values of C/D may bring the system through a bifurcating hierarchy of stable cycles up to a chaotic behaviour.

The domestic ducks (Anas platyrhynchos domesticus) are resistant to most of the highly pathogenic avian influenza virus (HPAIV) infections. In this study, we characterized the lung proteome and phosphoproteome of ducks infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala) at 12 hr, 48 hr and 5 days post infection condition. Total 2082 proteins were differentially expressed and 320 phosphorylation sites mapping to 199 phosphopeptides corresponding to 129 proteins were identified. Functional annotation of proteome data analysis reveals activation of RIG-I-like receptor and Jak-STAT signaling pathways, that lead to induction of interferon stimulated genes (ISGs) expression. The pathway analysis of phosphoproteome datasets also confirms the activation of RIG I, Jak-STAT signaling, NF-kappa B signaling and MAPK signaling pathways in the lung tissues. The induction of ISGs proteins (STAT1, STAT3, STAT5B, STAT6, IFIT5 and PKR) establishes protective antiviral immune response in duck lung tissue. Further, the protein-protein interaction network analysis identified proteins like AKT1, STAT3, JAK2, RAC1, STAT1, PTPN11, RPS27A, NFKB1 and MAPK1 as main hub proteins that might play important roles in disease progression in ducks. Together, functional annotation of proteome and phosphoproteome datasets reveals the molecular basis of the disease progression and disease resistance mechanism in ducks infected with HPAI H5N1 virus.

The objective of the study was to analyse the antimicrobial susceptibility trends of Spanish porcine bacteria to quinolones, cephalosporins and polymyxins. Isolates of Actinobacillus pleuropneumoniae, Pasteurella multocida, and Escherichia coli were isolated from sick pigs from 2019 to 2022. Antimicrobial susceptibility test was determined by minimal inhibitory concentration (MIC) following internationally accepted methodology. MIC categorization was based on distributing the range of MIC values in four categories being category one the most susceptible (lowest MIC value) and four the less susceptible one (highest MIC value). Moreover, clinical susceptibility (susceptible/resistant) was also determined according to CLSI and EUCAST clinical breakpoints. A logistic and multinomial logistic regression model was used to analyze the susceptibility data for dichotomized and categorized MIC data, respectively for any pair of antimicrobial/microorganism. In general terms, the antimicrobial susceptibility of pig bacteria to these antimicrobials remained stable or increased in the last four years in Spain. In the case of A. pleuropneumoniae and quinolones, it was observed a significant temporal trend where isolates from 2020 had significantly increased odds of being more susceptible than isolates from 2019. In the case of E. coli and polymyxins, a significant temporal trend was observed where isolates from 2020 and 2021 had significantly increased odds of being more susceptible than isolates from 2019 and 2020, respectively. Finally, a significant odd of being less susceptible was only observed for cephalosporins and E. coli for 2020 versus 2019, stagnating for the rest of study period. These results provide sound data on critical important antimicrobials in swine medicine.

Background: In the domestic pig, neural and non-neuronal cholinergic systems in the gallbladder and extrahepatic bile ducts need a detailed morphological study to identify the type and localization of their structural components. We aimed to quantitatively analyze biliary cholinergic ganglia and nerves as well as non-neuronal cholinergic cells; Methods: Immunohistochemical detection of choline acetyltransferase expression was performed to define cholinergic nerve and non-neuronal structures in gallbladder and extrahepatic bile ducts; Results: The number and dimensions of cholinergic ganglia, perikaryons and nerves forming ganglionic nerve plexuses in the propria, muscular and subserosal layers was estimated. The immunoexpression of choline acetyltransferase in biliary glandular cells and mast cells was also detected and analyzed. Conclusions: Qualitative and quantitative analysis of choline acetyltransferase positive nerves, ganglionic and non-ganglionic nerve plexuses of acetylcholine supplemented the morphological knowledge of the cholinergic innervation of the extrahepatic biliary pathways and non-neuronal sources: glandular cholinergic cells and cholinergic-type mast cells. Original data of the number and dimensions of intramural nerves, mast cells, ganglia and ganglion perikaryons could be used as reference values in the diagnosis of neuropathological processes in biliary pathways. Clarifying the precise mechanisms of gallbladder smooth muscle contractility will contribute to the improvement of therapeutic strategies to prevent biliary stasis and biliary disorders.

Multiplex genome editing may induce genotoxicity and chromosomal rearrangements due to double-strand DNA breaks at multiple loci simultaneously induced by programmable nucleases, including CRISPR/Cas9. However, recently developed base-editing systems can directly substitute target sequences without double-strand breaks. Thus, the base-editing system is expected to be a safer method for multiplex genome-editing platforms for livestock. Target-AID is a base editing system composed of PmCDA1, a cytidine deaminase from sea lampreys, fused to Cas9 nickase. It can be used to substitute cytosine for thymine in 3-5 base editing windows, 18 bases upstream of the protospacer-adjacent motif site. In the current study, we demonstrated Target-AID-mediated base editing in porcine cells for the first time. We targeted multiple loci in the porcine genome using the Target-AID system and successfully induced target-specific base substitutions with up to 63.15% efficiency. This system can be used for the further production of various genome-engineered pigs.

Abstract : Background : porcine cysticercosis is an endemic parasitic zoonosis in many developing countries. The objective was to estimate the seroprevalence of porcine cysticercosis in traditional pig farms in the departments of Dabou, Aboisso and Agboville where blood samples were taken from pigs and analyzed by ELISA (IgG) and western blot. Data on farming practices and pig characteristics were collected. Categorical variables were compared with the Chi2 test and continuous variables with the Student test. Multivariate logistic regression models were constructed to identify risk factors. Results: A total of 668 pigs were sampled from 116 farms. The seroprevalence of cysticercosis was estimated at 13.2%. Overweight [ORa=2.6; 95%CI(1.3-4.9)] and fat pigs [ORa=2.3; 95%CI(1.0-4.8)] were twice as likely to be seropositive for cysticercosis. This risk was increased in farms using well water for drinking [aOR=2.5; 95%CI(1.0-6.3)] as well as those reporting veterinary care of the animals (ORa=2.9; 95%CI (1.2-7.3)). Conclusions: This study demonstrated the circulation of T. solium in pig farms in southern Côte d'Ivoire.

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.

A major challenge for the dissemination, replication, and reuse of epidemiological forecasting studies during COVID-19 pandemics is the lack of clear guidelines and platforms to exchange models in a Findable, Accessible, Interoperable, and Reusable (FAIR) manner, facilitating reproducibility of research outcomes. During the beginning of pandemics, models were developed in diverse tools that were not interoperable, opaque without traceability and semantics, and scattered across various platforms - making them hard to locate, infer and reuse. In this work, we demonstrate that implementing the standards developed by the systems biology community to encode and share COVID-19 epidemiological models can serve as a roadmap to implement models as a tool in medical informatics, in general. As a proof-of-concept, we encoded and shared 24 epidemiological models using the standard format for model exchange in systems biology, annotated them with cross-references to data resources, packed up all associated files in COMBINE archives for easy sharing, and finally, disseminated the models through BioModels repository to significantly enhance their reproducibility and repurposing potential. We recommend the use of systems biology standards to encode and share models of epidemic and pandemic forecasts to improve their findability, accessibility, interoperability, reusability, and reproducibility.

Less aligned emphasis has been given to the COVID-19 infodemic coordinating with the COVID-19 outbreak. Global profusion of tangled monikers and hashtags has found their ways in daily communication and contributed to backlash against Chinese. Official naming efforts against infodemic should be meet with a fair share of identification. Based on brief critical reviews on previous multifarious naming practices, we punctuate heuristic introspection in scientific conventions and sociocultural paradigms. Infodemiological analysis promises to articulate that people around the globe are divided in their favor stigmatized monikers in the public and scientific communities because of perceptual bias. There is no positive correlation between the degree of infection in their territories and collective perceptual bias to COVID-19. The official portfolio “COVID-19” and “SARS-CoV-2” has not become de facto standard usages, but full-fledged official names are excepted to duly contribute to the resilience of negative perceptual bias and collective behavioral propensities.

This article investigates a proposed new mathematical model that considers the infected individuals using various rate coefficients such as transmission, progression, recovery and vaccination. The fact that the dynamic analysis is completely determined by the basic reproduction number is established. More specifically, local and global stabilities of the disease-free equilibrium and the endemic equilibrium are proved under certain parameter conditions when the basic reproduction number is below or above unity. A realistic computer simulation is performed for better understanding of the variations in trends of different compartments after the outbreak of the disease.

Susceptible, infective, recovered, and hospitalized/isolated individuals are placed on the cells of a nxn square lattice, where each cell is occupied by a single individual or is vacant. At discrete time units (typically one day each) all susceptibles and infectives execute a random movement and when a coincidence of the two types occurs the susceptible is converted to infective status according to some probability. Infectives are labelled by the number of days since originally infected. At each time increment the age label of the infectives is increased by one unit. When the label reaches a number like 15 or 20 days the susceptibles recover with some probability or become isolated/hospitalized. Upon reaching some age the latter types either recover or die. Probabilities for the movements and conversions from one status to another are implemented by random numbergeneration. Simulations were carried out to investigate the effect of several probability and age parameters, the size of population (proportional to nxn) and density (related to fraction of occupied cells), and the size of the movements. Mid-term gradual conversion of susceptibles to isolated was explored as intervention policy.

Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously [1]. In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.

Presentation of case: A 20 year old men from Simanjiro district in northern Tanzania presented with a 3 year history of splenomegaly, fatigue, cachexia, skin maculae and recent onset of watery diarrhea at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. Due to laboratory findings of pancytopenia, diagnostic workup included bone marrow aspiration cytology and biopsy. Although the rapid test (IT LEISH, rK39 RDT) was negative, blood smear showed amastigote forms of Leishmaniasis in macrophages. Repeat bone marrow aspiration and PCR eventually confirmed VL. The patient denied travel to known endemic areas of visceral leishmaniasis (VL). Treatment was initiated with Amphotericin B, but the patient died on the fourth day of treatment from respiratory insufficiency. An autopsy revealed massive organ manifestations of VL. Case discussion: This is the first reported autochthonous case of VL in Tanzania. Clark et al. detected the vector Phlebotomous martini in Northern Tanzania in 2013, in a region boardering the district of our patient. The negative rapid test draws attention to the fact that sensitivity and specificity was found to be low in East African VL patients as displayed earlier by a Kenyan study. Therefore, tissue samples (spleen or bone marrow) remain necessary for diagnosis. The variety of symptoms in this presented case was remarkable, including the occurrence of Post Kala Azar Dermal Leishmaniasis (PKDL) and VL at the same time. This has been described in East African VL cases before as well as the occurrence of chronic diarrhea. An elongated undiagnosed period likely led to a mixed clinical picture that included: hepato-splenomegaly, PKDL, cachexia, and diarrhea.

Chrysoeriol (CHE) is a flavonoid substance that exists in many plants and has various physiological and pharmacological effects, including anti-inflammatory, antioxidant, anti-tumor, and protective activity, especially for the cardiovascular system and liver. This study aimed to analyze the results and possible mechanisms of CHE on early porcine embryo development. Adding CHE to the culture media can improve the development quality of early porcine embryos. CHE significantly increased the blastocyst rate and total cell number of embryos in vitro. The apoptosis of blastocyst in CHE-treated culture also decreased significantly compared with untreated culture. Furthermore, CHE downregulated intracellular reactive oxygen species (ROS) and increased glutathione (GSH) in embryos. CHE was also shown to improve the activity of mitochondria and inhibit the occurrence of autophagy. In addition, antioxidant-related genes (SOD1, SOD2, and CAT) and cell pluripotency-related genes (SOX2, OCT4, and NANOG) were upregulated, while those related to apoptosis (Caspase 3) and autophagy (LC3B) showed a downward trend after supplementation with CHE. These results indicated that CHE improved the development of porcine embryos in vitro by reducing oxidative stress and autophagy levels.

This study explored the effects of pBD114 (porcine β-defensin 114) on inflammatory response. The results in RAW264.7 cells showed that 100 μg/mL of pBD114 significantly increased the concentrations of TNFα and IL-10, and 10 μg/mL of pBD114 significantly decreased the concen-tration of TNFα in LPS-induced RAW264.7 cell cultures at 10 ng/mL. These results suggest that pBD114 can exhibit pro-inflammatory or anti-inflammatory activities under certain conditions. RNA-seq analysis was performed to gain further insight into the effects of pBD114 on the in-flammatory response. Among pBD114 promoting RAW264.7 pro-inflammatory response, pBD114 significantly up-regulated 1170 genes and down-regulated 724 genes. KEGG enrichment found that the DEGs were significantly enriched in immune- and signal-transduction-related signaling pathways. PPI and KDA analyses revealed that Bcl10 and Bcl3 were the key genes. In addition, pBD114 significantly up-regulated 12 genes and down-regulated 38 genes in the an-ti-inflammatory response. KEGG enrichment analysis revealed that the DEGs were mainly en-riched in the "Cytokine-cytokine receptor interaction" signaling pathway, and PPI and KDA analyses showed that Stat1 and Csf2 were the key genes. The results of qRT-PCR verified those of RNA-seq. In vivo mice tests also confirmed the pro- or anti-inflammatory activity of pBD114. Although the inflammatory response is a rapid and complex physiological reaction to noxious stimuli, this study found that pBD114 plays an essential role in the inflammatory response mainly by acting on genes related to immunity, signal transduction, signaling molecules, and interactions.

Our study essentially concerns the dynamic behavior of an SIRS epidemic model in discrete time. Two equilibrium points are obtained; one is disease-free while the other is endemic. We are interested in the endemic fixed point as well as its asymptotic stability. Depending on the parameters which are estimated using the data from US Department of health and SIRS modelling with optimization, two Flip and Transcritical bifurcations appear. We illustrate their diagrams, as well as their bifurcation curves using the method of Carcasses \cite{carcasses1993determination,carcasses1995singularities} for the Flip bifurcation and by an implicit function deduced from such an equation for the Transcritical bifurcation. We use the scanning of the parametric plane to have a global view of the behavior of the model and to highlight the zones of stability of the existing singularities. A superposition of the bifurcation curves with the parametric plane can show the overlap of the curves with the boundaries of the stability domains, which confirms the smooth running of the simulation and its correspondence with the theory, we finish this article with constrained optimal control applied to infection rate and recruitment rate for an SIRS discrete epidemic model. Pontryagin's maximum principle is used to determine these optimal controls. Finally using COVID-19 data in the USA, we obtain results that demonstrate the effectiveness of the proposed control strategy to mitigate the spread of the pandemic.

Symmetry concepts in parametrized dynamical systems may reduce the number of external parameters by a suitable normalization prescription. If, under the action of a symmetry group G, parameter space A becomes a (locally) trivial principal bundle, A ~ A/G x G, then the normalized dynamics only depends on the quotient A/G. In this way, the dynamics of fractional variables in homogeneous epidemic SI(R)S models, with standard incidence, absence of R-susceptibility and compartment independent birth and death rates, turns out to be isomorphic to (a marginally extended version of) Hethcote's classic endemic model, first presented in 1973. The paper studies a 10-parameter master model with constant and I -linear vaccination rates, vertical transmission and a vaccination rate for susceptible newborns. As recently shown by the author, all demographic parameters are redundant. After adjusting time scale, the remaining 5-parameter model admits a 3-dimensional abelian scaling symmetry. By normalization we end up with Hethcote's extended 2-parameter model. Thus, in view of symmetry concepts, reproving theorems on endemic bifurcation and stability in such models becomes needless.

This paper studies pandemic viruses that spread during the period (1759–2020) according to solar activity cycles. Our findings and results include the following: (1) The severity of a pandemic correlates negatively with the strength of solar activity; (2) Pandemic viruses are classified into three types based on their compatibility with solar activity associations. Most of them spread through the quiet Sun, where viruses survive better in cold and rainy weather, and in stable geomagnetic fields without strong disturbances; (3) The emergence of new strains of influenza viruses was manifested in two ways. First, the annual epidemics due to antigenic drift. Second, pandemics recur every 1–12 solar cycles (about 11–120 years) due to viral reassortment of new subtypes, which results in antigenic shifts; (4) Pandemic viruses have two groups according to their recurring period: first, recurring in nine solar cycles; second, recurring in twelve solar cycles. Furthermore, we reassort pandemic viruses from their previous spread in the same periodic classification. Moreover, we derive a periodicity formula for each subtype of the pandemic virus as a spread date.

This study aimed to evaluate the effects of feeding spray-dried porcine plasma (SDPP) on the protection afforded by the BA71∆CD2 African swine fever virus (ASFV) vaccine prototype. Two groups of pigs ac-climated to diets without or with 8% SDPP were intranasally inoculated with 105 plaque forming units (PFU) of live attenuated ASFV strain BA71∆CD2 and three weeks later left in direct contact with pigs infected with the pandemic Georgia2007/01 ASFV strain. During the post-exposure (pe) period, 2/6 from the conventional diet group showed a transient peak rectal temperature >40.5ºC before day 20 pe and some tissue samples collected at 20 d pe from 5/6 were PCR+ for ASFV, albeit showing Ct values much higher than Trojan pigs. Interestingly, the SDPP group did not show fever, neither PCR+ in blood nor rectal swab at any time pe and none of the postmortem collected tissue samples were PCR+ for ASFV. Differential serum cytokine profiles among groups at vaccination, and a higher number of ASFV-specific IFNϒ-secreting T-cells in pigs fed with SDPP soon after the Georgia2007/01 encounter, confirmed the relevance of Th1-like responses in ASF pro-tection. We believe that our result show that nutritional interventions might contribute to improve future ASF vaccination strategies.

In India the first case of coronavirus disease 2019 (COVID-19) reported on 30 January 2020, and thereafter cases were increasing daily after the last week of Feb. 2020. COVID-19 identified as family member of coronaviridae where previously Middle East Respiratory Syndrome MERS and Severe Acute Respiratory Syndrome SARS belongs to same family. The COVID-19 attacks on respiratory system signing fever, cough and breath shortness, in severe cases may cause pneumonia, SARS or some time death. The aim of this study work is to develop model which predicts the epidemic peak for COVID-19 in India by using the real-time data from 30 Jan to 10 May 2020. There are uncertainties while identifying the population information due to the incomplete and inaccurate data, we initiate the most popular model for epidemic prediction i.e Susceptible, Exposed, Infectious, & Recovered SEIR initially the compartmental model for the prediction. Based on the solution of the state estimation problem for polynomial system with Poisson noise, we estimate that the epidemic peak may reach the early-middle July 2020, initializing recovered R0 to 0 and Infected I0 to 1. The outcomes of the model will help epidemiologist to isolate the source of the disease geospatially and analyze the death. Also government authorities will be able to target their interventions for rapidly checking the spread of the epidemic.

Fowlpox virus (FPV) has been used as a vector for many years. To date, surprisingly, very little data exist on the persistence of fowlpox vaccines in chicken tissues, or what kind of immune cells respond to the vaccination at the site of inoculation. Although both humoral and cellular mediated immunity (CMI) play a part in overall immunity against FPV, little is known regarding the cell-mediated immune responses to FPV infection. The main aim of this paper was to measure persistence of the recombinant fowlpox vaccine in the skin tissues following vaccination. The results showed that the recombinant FPVs do not persist for long, and are cleared by 6 days post-vaccination (dpv). The response of immune cells (macrophages, B cells, CD4+ and CD8+ T cells) that infiltrating the site of vaccination was estimated.

Chikungunya virus (CHIKV), a single-stranded RNA virus transmitted by Aedes mosquitoes, poses a significant global health threat, with severe complications observed in vulnerable populations. The only licensed vaccine, IXCHIQ, approved by the USFDA, is insufficient to address the growing disease burden, particularly in endemic regions lacking herd immunity. Monoclonal antibodies (mAbs), explicitly targeting structural proteins E1/E2, demonstrate promise in passive transfer studies, with mouse and human-derived mAbs showing protective efficacy. The article explores various vaccine candidates, including live attenuated, killed, nucleic-acid-based (DNA/RNA), virus-like particle, chimeric, subunit, and adenovirus vectored vaccines. RNA vaccines emerge as promising candidates due to their rapid response capabilities and enhanced safety profile. The review underscores the importance of E1 and E2 proteins as immunogens, emphasising their antigenic potential. Several vaccine candidates, such as CHIKV/IRES, measles vector (MV-CHIK), synthetic DNA-encoded antibodies, and mRNA-lipid nanoparticle vaccines, demonstrate encouraging preclinical and clinical study results. In addition to identifying potential molecular targets for antiviral therapy, the study looks into the roles played by Toll-like receptors, RIG-I, and NOD-like receptors in the immune response to CHIKV. It also offers insights into novel tactics and promising vaccine candidates.

Porcine sapovirus (PoSaV) is a significant pathogen causing diarrhea with high morbidity and mortality rates. Given its zoonotic characteristics, this study conducts a comprehensive genetic evolutionary analysis of PoSaV. Results confirmed PoSaV as the primary RNA virus in piglet feces (27.54%). Phylogenetic analysis identifies the prevalent PoSaV strain SHCM/Mega2023 in the GIII genogroup, involving a recombinant event with MK962338 and KT922089. The time tree revealed that the GIII genogroup exhibits the widest divergence time span, indicating a high likelihood of viral recombination. Further selective pressure calculations demonstrate that PoSaV was under purifying selection (dN/dS &lt; 1), with seven positively selected sites in VP1 protein which might be related to the antigencity. In conclusion, this study presents a novel genomic evolution of PoSaV, offering valuable insights into antigenicity and vaccine research.

It is important to be able to detect and differentiate between distinct porcine enteric coronaviruses that can cause similar diseases. However, the existence of naturally occurring recombinant coronaviruses such as swine enteric coronavirus (SeCoV) can give misleading results with currently used diagnostic methods. Therefore, we have developed and validated three duplex real-time quantitative RT-PCR assays for the simultaneous detection of, and differentiation between, porcine epidemic diarrhea virus (PEDV) and SeCoV. Transmissible gastroenteritis virus (TGEV) is also detected by two out of these three assays. In addition, a novel triplex assay was set up that was able to detect and differentiate between these alphacoronaviruses and the porcine deltacoronavirus (PDCoV). The validated assays have low limits of detection, close to 100% efficiency and were able to correctly identify the presence of PEDV and SeCoV in 55 field samples, while 20 samples of other pathogens did not give a positive result. Implementing one or more of these multiplex assays into the routine diagnostic surveillance for PEDV will ensure that the presence of SeCoV, TGEV and PDCoV will not go unnoticed.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

Background: Patterns of humoral immune responses represent a major hurdle in terms of pig-to-human xenotransplantation approaches. The best-known xenogeneic glycan antigens pre-sent in pigs are the αGal (Galili-antigen) and the non-human sialic acid Neu5Gc. As there are further differences between porcine and human cellular surface glycosylation, a much broader range of glycan epitopes with xeno-reactive relevance can be anticipated. Therefore, we set-out to chemically modify porcine cellular surface glycans in a global approach by applying sodium peri-odate (NaIO4) oxidation. Methods: Porcine endothelial cells were exposed to oxidation with 1 to 5 mM NaIO4 for different time periods at 37°C or 4°C and under static or dynamic conditions. The impact on cellular sur-vival was determined applying live/dead-assays. Oxidation of αGal-epitopes was assessed by flu-orescence microscopy-based quantification of isolectin-B4 (IL-B4) staining. Overall immunogenic-ity of porcine cells was determined by human serum antibody binding. Results: Treatment of porcine endothelial cells and tissues with NaIO4 led to a reduced binding of the αGal-specific IL-B4 and/or human serum antibodies. NaIO4 revealed to be cytotoxic when performed at elevated temperature and for prolonged time. However, by applying 2 mM NaIO4 for 60 min at 4°C a high extent of cellular viability and a relevant reduction of detectable αGal epitope were observed. No differences were detected irrespectively on whether the cells were oxi-dized under static or flow conditions. Conclusion: Glycan epitopes on living cells can be oxidized with NaIO4 while maintaining their viability. Accordingly, this strategy holds promise to prevent immune reactions mediated by pre-formed anti-glycan antibodies.

This study presents a dynamic modeling approach to investigate the impact of saturation dynamics on HIV/AIDS transmission in the presence of vertical transmission and treatment strategies. The proposed model incorporates disease-free and endemic equilibria, with a focus on analyzing the basic reproduction number and conducting stability analysis. Results indicate that the disease-free equilibrium is locally asymptotically stable under certain conditions. The findings suggest that a combination of treatment interventions and awareness campaigns, along with other control measures, may play a crucial role in curbing the spread of the HIV/AIDS virus. This research contributes to understanding the complex dynamics of HIV/AIDS epidemics and highlights the importance of considering saturation effects in epidemic modeling.

The original purpose of this article was to modify the original SIR equations to allow for a direct source of infection (without which the original equations would have no solutions unless one starts with an already infected population) and also to see to what extent one could obtain multiple outbreaks of an infectious disease. In the course of developing the basic ideas several other factors arose to take prominent roles.Perhaps one of the more salient factors is the point that choosing an arbitrary time to change conditions from say a lock-down for the population to a less stringent social behavior, such as allowing partial or complete opening of businesses and schools, etc. should be based on knowledge of the disease and its evolution. Such decisions are usually made by politicians who have less than full information concerning the consequences of their actions. Several examples are given to illustrate these points.

Epidemic diseases that arise from infectious RNA viruses, particularly influenza viruses, pose a constant threat to the global economy and public health. Viral evolution has undermined the efficacy of acquired immunity from vaccines and the antiviral effects of FDA-approved drugs. As such, there is an urgent need to develop new antiviral lead agents. Natural compounds, owing to their historical validation of application and safety, have become a promising solution. In this light, a novel marine bacterium, Pseudomonas sp. M20A4R8, has been found to exhibit significant antiviral activity [half maximal inhibitory concentration (IC50) = 1.3 µg/mL, selectivity index (SI) = 919.4] against influenza virus A/Puerto Rico/8/34, surpassing the activity of chloroquine. The antiviral response by M20A4R8 extract was induced during post-entry stages of the influenza virus, indicating suitability for post-application after the establishment of viral infection. Furthermore, post-treatment with M20A4R8 extract protected the host from virus-induced apoptosis, suggesting its potential use in acute respiratory disease complexes resulting from immune effectors' overstimulation and autophagy-mediated self-apoptosis. The extract demonstrated an outstanding therapeutic index against influenza virus A/Wisconsin/15/2009 (IC50 = 8.1 µg/mL, SI = 146.2) and B/Florida/78/2015 Victoria lineage (IC50 = 3.5 µg/mL, SI = 343.8), indicating a broad anti-influenza virus activity with guaranteed safety and effectiveness. This study provides a new perspective on mechanisms for preventing a broad spectrum of viral infections through antiviral agents from novel and natural origins. Future studies on a single or combined compound from the extract hold promise, encouraging its use in preclinical challenge tests with various influenza virus strains.

Childhood diarrhea continues to be a major cause of under-five (U-5) mortality globally and in India. In this study, 1571 U-5 children residing in nine rural villages and four urban slums in Ujjain, India were included with the objective to use community participation and drug utilization research to improve diarrheal case management. The mean age was 2.08 years, with 297 (19%), children living in high diarrheal index households. Most mothers (70%) considered stale food, teething (62%), and hot weather (55%) as causes of diarrhea. Water, sanitation, and hygiene (WASH)-related characteristics revealed that most (93%) households had toilets, but only 23% of the children used them. The study identified ineffective household water treatment by filtration through cloth by most (93%) households and dumping of household waste on the streets (89%). The results revealed low community awareness of correct causes of diarrhea (poor hand hygiene, 21%; littering around the household, 15%) and of correct diarrhea treatment (oral rehydration solution (ORS) and zinc use, 29% and 11%, respectively) and a high antibiotic prescription rate by healthcare providers (83%). Based on the results of the present study, context-specific house-to-house interventions will be designed and implemented.

Recently, selection in pigs has been focused on improving the lean meat content in carcasses; this focus has been most evident in breeds constituting a paternal component in breeding. Such sire-breeds are used to improve the meat quantity of cross-breed pig lines. However, even in one breed, a significant variation in the meatiness level can be observed. In the present study, the comprehensive analysis of genes and microRNA expression profiles in porcine muscle tissue was applied to identify the genetic background of meat content. The comparison was performed between whole gene expression and miRNA profiles of muscle tissue collected from two sire-line pig breeds (Piertain, Hampshire). The RNA-seq approach allowed the identification of 627 and 416 differentially expressed genes (DEGs) between pig groups differing in terms of loin weight between Pietrain and Hampshire breeds, respectively. The comparison of miRNA profiles showed differential expression of 57 microRNAs for Hampshire and 34 miRNAs for Pietrain pigs. Next, 43 genes and 18 miRNAs were selected as differentially expressed in both breeds and potentially related to muscle development. According to Gene Ontology analysis, identified DEGs and microRNAs were involved in the regulation of the cell cycle, fatty acid biosynthesis and regulation of the actin cytoskeleton. The most deregulated pathways dependent on muscle mass were the Hippo signalling pathway connected with the TGF-beta signalling pathway and controlling organ size via the regulation of ubiquitin-mediated proteolysis, cell proliferation and apoptosis. The identified target genes were also involved in pathways such as the FoxO signalling pathway, signalling pathways regulating pluripotency of stem cells and the PI3K-Akt signalling pathway. The obtained results indicate molecular mechanisms controlling porcine muscle growth and development. Identified genes (SOX2, SIRT1, KLF4, PAX6 and genes belonging to the transforming growth factor beta superfamily) could be considered candidate genes for determining muscle mass in pigs.

A relevant aspect in the epidemiology of Tegumentary Leishmaniasis (TL) is the Leishmania parasites carrying a viral endosymbiont Leishmania RNA Virus 1 (LRV1), a dsRNA virus. Leishmania parasites carrying LRV1 are prone to causing more severe TL symptoms, increasing the likelihood of unfavorable clinical outcomes. LRV1 has been observed in cultured strains of five L. (Viannia) species, and host specificity was suggested when studying LRV1 from L. braziliensis and L. guyanensis strains. The coevolution hypothesis of LRV1 and Leishmania was based on phylogenetic analyses, implying an association between LRV1 genotypes, Leishmania species, and their geographic origins. This study aimed to investigate LRV1 specificity to Leishmania (Viannia) species hosts by analyzing LRV1 from L. (Viannia) species. To this end, LRV1 was screened in L. (Viannia) species other than L. braziliensis or L. guyanensis, and it was detected in 11 out of 15 L. naiffi and in 2 out of 4 L. shawi. Phylogenetic analyses based on partial LRV1 genomic sequencing supported the hypothesis of host specificity, as LRV1 clustered according to their respective Leishmania species hosts. These findings underscore the importance of investigating Leishmania and LRV1 coevolution and its impact on Leishmania (Viannia) species dispersion and pathogenesis in the American Continent.

The Dark Web is known as a place triggering a variety of criminal activities. Anonymization techniques enable illegal operations, leading to the loss of confidential information and its further use as bait, a trade product or even a crime tool. Despite technical progress, there is still not enough awareness of the Dark Web and its secret activity. In this study, we introduced the Dark Web Enhanced Analysis (DWEA), in order to analyze and gather information about the content accessed on the Dark Net based on data characteristics. The research was performed to identify how the Dark Web has been influenced by recent global events, such as the COVID-19 epidemic. The research included the usage of a crawler, which scans the network and collects data for further analysis with machine learning. The result of this work determines the influence of the COVID-19 epidemic on the Dark Net.

While there are many models of epidemic evolution perhaps the basis for such models finds itself in the lumped behavior expressed through the so-called SIR model (Susceptible, Infectious, Recovered) from which spring many related models. This paper discusses multiple analytic solutions to that equation including those that are available in closed analytic form and those for which at least one final integral has to be done numerically, so-called quasi-analytic solutions. The solutions are intrinsically time-dependent of course. The hope is that such an investigation will lead to a better understanding of when and how models can be of use in studying the dynamical evolution of diseases including, perhaps, the great influenza pandemic of 1918 together with later pandemics and epidemics not excluding the Covid-19 pandemic of the present day.

We present a new mathematical model of disease spread reflecting specialties of covid-19 epidemic by elevating the role social clustering of population. The model can be used to explain slower approaching herd immunity in Sweden, than it was predicted by a variety of other mathematical models; see graphs Fig. \ref{GROWTH2}. The hierarchic structure of social clusters is mathematically modeled with ultrametric spaces having treelike geometry. To simplify mathematics, we consider homogeneous trees with $p$-branches leaving each vertex. Such trees are endowed with algebraic structure, the $p$-adic number fields. We apply theory of the $p$-adic diffusion equation to describe coronavirus' spread in hierarchically clustered population. This equation has applications to statistical physics and microbiology for modeling {\it dynamics on energy landscapes.} To move from one social cluster (valley) to another, the virus (its carrier) should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider {\it linearly increasing barriers.} This structure matches with mild regulations in Sweden. The virus spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This behavior matches with the covid-19 epidemic, with its cluster spreading structure. Our model differs crucially from the standard mathematical models of spread of disease, such as the SIR-model. We present socio-medical specialties of the covid-19 epidemic supporting our purely diffusional model.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

Aortic aneurysms (AA) occur in 4.8% of people causing 150,000 deaths annually. While endovascular aneurysm repairs reduce surgical morbidity, device-related failures (leak/displacement) are frequent highlighting the need for test models that better represent the mural geometry and compliance changes in human AAs. We aimed to develop and characterise an ex vivo porcine aortic model of AA. The optimal duration of tissue elastase exposure to emulate AA changes in elastin microstructure and content was determined using porcine aortic rings. Elastase-induced changes were quantified morphologically, and mechanical properties assessed via ring tensile testing. Subsequent experiments tested the potential for localised elastase treatment in a 1 cm segment of porcine aorta using a specially designed 3D printed test rig. The effect on pressure-diameter behaviour was investigated via inflation-extension testing. Elastase treatment produced time dependent decreases in elastin, resulting in an increased tensile modulus and circumferential length in the ring samples in the final phase of the J-shaped tissue stress-strain curves. In whole aortic segments, localised elastase-induced luminal degradation was successfully limited to a central region. The degree of elastin degradation achieved was sufficient to cause localised dilation with respect to controls under physiological pressures. Localised elastin degradation in porcine aortic segments is feasible and emulates the changes seen clinically in aortic aneurysms.

Porcine circovirus type 2 (PCV2) is responsible for a number of porcine circovirus associated diseases (PCAD) that can severely impact domestic pig herds. For a non-enveloped virus with a small genome (1.7 kb ssDNA), PCV2 is remarkably diverse, with 8 subtypes (a-h). New subtypes of PCV2 can spread through migration of wild boars, which are thought to infect domestic pigs and spread further through the domestic pig trade. Despite a large swine population, the diversity of PCV2 subtypes in Ukraine has been undersampled, with few PCV2 genome sequences reported in the past decade. To gain a deeper understanding of PCV2 subtype diversity in Ukraine, samples of blood serum were collected from wild boars (n = 107) that were hunted in Ukraine during the November-December 2012 hunting season. We found 34/107 (31.8%) prevalence of PCV2 by diagnostic PCR. For domestic pigs, liver samples (n = 16) were collected from a commercial market near Kharkiv in 2019, of which 6/16 (37%) were positive for PCV2. We sequenced the genotyping locus ORF2, a gene encoding the PCV2 viral capsid (Cp), for 11 wild boar and 6 domestic pig samples in Ukraine using an Oxford Nanopore MinION device. Of 17 samples with resolved subtypes, PCV2 subtype b was most common in wild boar (10/11, 91%), while domestic pigs were infected with subtypes b and d. We also detected subtype b/d and b/a co-infections in wild boar and domestic pigs, respectively, and subtype f in a wild boar from Poltava for the first time in Ukraine. Building a maximum likelihood phylogeny, we identified a sublineage of PCV2 subtype b infections in both wild and domestic swine, suggesting a possible epizootic cluster and ecological interaction in northeastern Ukraine.

Clostridioides (Clostridium) difficile is an enteric pathogen of neonatal pigs with zoonotic transmission remaining a significant problem in humans, including nosocomial resurgence, following oral administration of broad-spectrum antibiotics. To date, the immune response to C. difficile has mostly focused on neutrophils and cytokine/chemokines, particularly in human infection. We show that porcine monocytes respond to C. difficile differently compared with many other bacterial infections. Infection of porcine monocytes with human C. difficile strains CD630 (Ribotype 078) or R20291 (Ribotype 027) for 3 or 24h post-infection (pi) resulted in a lack of oxidative burst or nitrite ion production when compared to uninfected controls (P >0.05). The survival dynamics of both CD630 and R20291 in monocytes were similar with intracellular bacterial numbers being similar at 3h pi and 24h pi (P >0.05). However, we show that porcine monocytes entrap C. difficile via extracellular DNA traps. This process began as early as 3h pi and at 24h pi the nuclei appeared to be depleted of DNA, although extracellular DNA was associated with the cell membrane. Our preliminary study also suggests that entrapment of C. difficile by extracellular DNA may occur via a process of monocyte etosis.

Recently, astroviruses (AstVs) have been associated with neurological symptoms in pigs, cattle, sheep, minks, muskoxes, alpacas, and humans. To investigate genotypes of porcine astrovirus (PAstV) and neuroinvasive (Ni) PAstV in South Korea, five domestic pigs with neurological symptoms from three farms were tested using reverse transcriptase PCR, histopathology, and in situ hybridization (ISH). All five genotypes of PAstV were detected in brain tissues and coinfection of PAstV with multiple genotypes was observed. To the best of our knowledge, this is the first study to report pig infection by Ni-PAstV with multiple genotypes in South Korea.

The first attempt to control and mitigate an epidemic outbreak caused by a previously unknown virus occurs primarily via non-pharmaceutical interventions (NPIs). In case of the SARS-CoV-2 virus, which since the early days of 2020 caused the COVID-19 pandemic, NPIs aimed at reducing transmission enabling contacts between individuals. The effectiveness of contact reduction measures directly correlates with the number of individuals adhering to such measures. Here, we illustrate by means of a very simple compartmental model how partial noncompliance with NPIs can prevent these from stopping the spread of an epidemic.

The influenza virus has been the primary cause of the pandemic, posing a constant threat to human society. Due to its genetic evolution and continuous outbreak, antiviral research currently focuses on exploring a novel lead agent. A comprehensive antiviral screening discovered a marine bacterium whose extract exerted excellent efficacy against influenza viruses. Parerythrobacter sp. M20A3S10, a novel strain under the family Erythrobacteraceae, could produce carotenoids exhibiting antiviral and anticancer activity by enhancing the cellular immune system. Post-treatment of M20A3S10 extract showed outstanding therapeutic indexes: against influenza virus A/PR8 (H1N1) [selectivity index (SI) = 24.0], A/Wisconsin/15/2009 (H3N2) (SI = 30.1) and B/Florida/78/2015 (SI = 38.2). Comparably, the effectiveness was demonstrated against Zika virus (ZIKV) and dengue virus type 2 (DENV2) with an SI of 22.5 and 24.1, respectively, namely broad-spectrum activity. Of note, the antiviral responses resulted from the common replication mechanism between IAV, ZIKV, and DENV2. The stimulation of apoptosis-mediated cellular immunity prevented the viral release and protected the host, suggesting that switching from necroptosis to apoptosis is a novel antiviral target. Although the specific compound affecting the antiviral activity was not identified, its promising efficacy with broad activity will contribute to developing a strategy for preventing future pandemics.

Immunosenescence refers to age-related alterations of the immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review the clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV), which include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 32. Our preliminary evaluation of published results and interim analyses of the RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Phoenixin-14 (PNX) - a bioactive peptide recently discovered in the rat brain, is highly conserved among many animal species: rodents (rat, mouse), pig, dog as well as humans. In rodents, PNX is expressed in areas responsible for the transmission of sensory information dorsal root ganglia (DRG) neurons, where it is present at relatively high levels and may preferentially suppress visceral pain. However, so far the presence of PNX has not been investigated in DRG in pigs, a species which, due to its anatomical and histological similarity to humans, is considered a better model for biomedical studies than rodents. The present study aimed to investigate the immunoreactivity of PNX in the DRG of the domestic pig. The collected spinal ganglia from the cervical (C), thoracic (Th), lumbar (L) and sacral (S) sections were transversely divided into serial sections of 10 μm thickness. DRG sections from each level of the spinal cord were double-labeled immunohistochemically using antibodies to PNX in a mixture with antibodies to: cocaine and amphetamine related transcript (CART), calretinin (CRT), calcytonin gene-related peptide (CGRP), galanin (GAL), nitric oxide synthase (nNOS), pituitary adenylate cyclase-acrivating polypeptide (PACAP), substance P (SP) or somatostatin (SOM), respectively. Immunohistochemical studies revealed PNX immunoreactivity in approximately 20% of nerve cells in all DRG examined, highlighting mainly the presence of the peptide in cells of small diameter (approximately 74% of all PNX-positive neurons found). Double labeling of DRG sections showed that PNX-immunopositive neurons stained also for CGRP (96.1%), SP (88.5%), nNOS (52.1%), GAL (20.7%), CRT (10.05%), PACAP (7.4%), CART (5.1%), or SOM (4.7%). Our research revealed for the first time the presence of the new peptide PNX in the sensory ganglia of the domestic pig, its co-localization with other important neurotransmitters involved in sensory transmission and its percentage distribution in ganglion domains. The exact function of PNX in DRG is not yet known, however, the high degree of co-localization of this peptide with the main nociceptive transmitters SP and CGRP may indicate its function in modulation of pain transmission.

Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined by in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was totally stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs were closer to those in humans than to those in mice.

We applied a generalized SEIR epidemiological model to the recent SARS-CoV-2 outbreak in the world, with a focus on Italy and its Lombardia, Piemonte, and Veneto regions. We focus on the application of a stochastic approach in fitting the model numerous parameters using a Particle Swarm Optimization (PSO) solver, to improve the reliability of predictions in the medium term (30 days). We analyze the official data and the predicted evolution of the epidemic in the Italian regions, and we compare the results with data and predictions of Spain and South Korea. We link the model equations to the changes in people’s mobility, with reference to Google’s COVID-19 Community Mobility Reports. We discuss the effectiveness of policies taken by different regions and countries and how they have an impact on past and future infection scenarios.

An influenza A virus (H3N2) with an envelope with the same structure as COVID-19 was used for antiviral testing of material surfaces, in comparison with some results of feline calicivirus. The evaluation method used was the film adhesion method, in which the virus solution is placed on the material and adhered to it using a film. The evaluation method was based on the film adhesion method, in which the virus solution is placed on the material and adhered with a film, and the plaque method, in which the cell virus is allowed to infect the material and form plaques, but the appropriate virus concentration must be adjusted to observe the plaques. When not under that restriction, the plaques are often incomplete; this is observed. For this reason, this study applied an area measurement method that can reflect viral activity even when plaques are not obtained. This study revealed that different types of metallic materials have different antiviral properties. Specifically, the antiviral activity of iron, carbon steel, and nickel was relatively high, while that of stainless steel and titanium was relatively low. The order of antiviral activity was as follows: Fe, SS400, Ni, SUS316L, SUS304, and Ti.

We study epidemic spreading in complex networks by a multiple random walker approach. Each walker performs an independent simple Markovian random walk on a complex undirected (ergodic) random graph where we focus on Barabási-Albert (BA), Erdös-Rényi (ER) and Watts-Strogatz (WS) types. Both, walkers and nodes can be either susceptible (S) or infected and infectious (I) representing their states of health. Susceptible nodes may be infected by visits of infected walkers, and susceptible walkers may be infected by visiting infected nodes. No direct transmission of the disease among walkers (or among nodes) is possible. This model mimics a large class of diseases such as Dengue and Malaria with transmission of the disease via vectors (mosquitos). Infected walkers may die during the time span of their infection introducing an additional compartment D of dead walkers. Infected nodes never die and always recover from their infection after a random finite time. This assumption is based on the observation that infectious vectors (mosquitos) are not ill and do not die from the infection. The infectious time spans of nodes and walkers, and the survival times of infected walkers, are represented by independent random variables. We derive stochastic evolution equations for the mean-field compartmental populations with mortality of walkers and delayed transitions among the compartments. From linear stability analysis, we derive the basic reproduction numbers R M , R 0 with and without mortality, respectively, and prove that R M < R 0 . For R M , R 0 > 1 the healthy state is unstable whereas for zero mortality a stable endemic equilibrium exists (independent of the initial conditions) which we obtained explicitly. We observe that the solutions of the random walk simulations in the considered networks agree well with the mean-field solutions for strongly connected graph topologies, whereas less well for weakly connected structures and for diseases with high mortality. Our model has applications beyond epidemic dynamics, for instance in the kinetics of chemical reactions, the propagation of contaminants, wood fires, among many others.

Our aim is to provide an insight of the procedures and the dynamics that lead the spread of contagious diseases through populations. Our simulation tool can increase our understanding on the spatial parameters which affect the diffusion of a virus. SIR models are based on the hypothesis that populations are “well mixed”. Our model constitutes an attempt to focus on the effects of the specific distribution of the initially infected individuals through the population and provide insights, considering the stochasticity of the transmission process. For this purpose, we represent the population using a square lattice of nodes. Each node represents an individual that may or may not carry the virus. Nodes that carry the virus can only transfer it to susceptible neighboring nodes. This important revision of the common SIR model provides a very realistic property: the same number of initially infected individuals can lead to multiple paths, depending on their initial distribution in the lattice. This property creates better predictions and probable scenarios to construct a probability function and appropriate confidence intervals. Finally, this structure permits realistic visualizations of the results to understand the procedure of contagion and spread of a disease and the effects of any measures applied.

In this paper we provide an ``expository overview" of classic epidemic projection models. Starting with the simple case of an epidemic that grows exponentially we then investigate ``compartmental" models. These assume that the growth of an infected population is limited endogenously by the size of the underlying pool of susceptibles. We then describe a new family of so-called "Exo-r" statistical models, which hinge on an exogenously driven growth rate of the infected population. This family, which can be used to model both infections and deaths, captures parsimoniously both the depletion of susceptibles and the effect of interventions such as lockdowns and ``social distancing". The model is used to fit numbers of Covid-19 infections in China. It is also used to model and project deaths in the United States. Results are used to inform a discussion on i) the challenges at hand and ii) the extent to which epidemic projection models may be useful despite being wrong.

Non-pharmacological interventions in the fight against COVID 19 include: a) suppression, which facilitates its extinction; and b) mitigation, which reduces its speed of spread. Left unmitigated, the intensive care unit bed capacity (ICU) is exceeded over its maximum supply, resulting in increased deaths. Suppression has shown in simulation models the potential for decreasing ICU occupation below its surge limit, effectively decreasing mortality. However, for avoiding a rebound in transmission, suppression must be maintained intermittently until a vaccine is available (which may take up to 2 years). The objective of this paper was to describe the mortality patterns observed in Spain, Italy and South Korea for discussing a hypothetical combined public health policy and socioeconomic model that could potentially reduce mortality while reducing the economic impact of this pandemic in Spain. The plan is based on a progressive-voluntary reinstatement to work of the population exposed to the lowest risks (healthy non-immune family units <50 y/o and immune population) and it depends on having sufficiently available ICU beds for providing adequate support. This model, if proven correct for Spain, could eventually be followed by other countries facing a similar impact of the present pandemic.

In this paper, we propose a new mathematical model based on the association between susceptible and recovered individual, where the association between susceptible and recovered individual is disturbed by white noise. This model is based on demographic changes and is used for long term behavior. We study the stability of equilibria of the deterministic model and prove the conditions for the extinction of diseases. Then, we investigate and obtain the critical condition of the stochastic epidemic model for the extinction and the permanence in mean of the disease with the white noise. To verify our results, we present some numerical simulations for real data related to disease.

Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Recent epidemiological studies conducted in developing countries identified Shigella species as the most predominant pathogenic bacteria responsible for diarrhea. Antimicrobial therapy is necessary for Shigella infections; however, the rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. To identify alternative antimicrobial compounds with activity against Shigella species, the pathogens responsible for bacterial diarrhea. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing benzothiazoles backbone, and their combination with certain antibiotics. In continuation to our effort in searching potent antimicrobial compounds, we have found this time around that two acetaminophen derivatives containing benzothiazoles backbone (4a and 4b) could inhibit the growth of Shigella flexneri with common MIC value of 12.5 µg/ml. These compounds were established through a time-kill kinetics’ study to be bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a & b) were found to be poorly active (MIC: 100 µg/ml) against this pathogen. Combination studies of 4a and 4b with the least susceptible antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity. The present study demonstrates that the azobenzothiazole dyes 4 (a & b) can be repurposed as potential anti-Shigella compounds, which can serve as scaffolds for the development of new agents against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries.

Human influenza A viruses (IAVs) cause global pandemics and epidemics. These viruses evolve rapidly, making current treatment options ineffective. To identify novel modulators of IAV-host interactions, we re-analyzed our recent transcriptomics, metabolomics, proteomics, phosphoproteomics, and genomics/virtual ligand screening data. We identified 713 potential modulators targeting 200 cellular and two viral proteins. Anti-influenza activity for 48 of them has been reported previously, whereas the antiviral efficacy of the remaining 665 is unknown. Studying anti-influenza efficacy, immuno-modulating properties and potential resistance of these compounds or their combinations may lead to the discovery of novel modulators of IAV-host interactions, which might be more effective than the currently available anti-influenza therapeutics.

Results from an explorative study revealing spatio-temporal patterns of the SARS-CoV-2/COVID-19 epidemic in Germany are presented. We dispense with contestable model assumptions and show the intrinsic spatio-temporal patterns of the epidemic dynamics. The analysis is based on COVID-19 incidence data, which are age-stratified and spatially resolved at the county level, provided by the Federal Government’s Public Health Institute of Germany (RKI) for public use. Although the 400 county-related incidence time series show enormous heterogeneity both with respect to temporal features as well as spatial distributions, the counties’ incidence curves organise into well distinguished clusters that coincide with East and West Germany. The analysis is based on dimensionality reduction, multidimensional scaling, network analysis, and diversity measures. Dynamical changes are captured by means of difference-in-difference methods which are related to fold changes of the effective reproduction numbers. The age-related dynamical patterns suggest a considerably stronger impact of children, adolescents and seniors on the epidemic activity than previously expected. Besides these concrete interpretations, the work mainly aims at providing an atlas for spatio-temporal patterns of the epidemic which serves as a basis to be further explored with the expertise from different disciplines, particularly sociology and policy makers. The study should also be understood as a methodological contribution to getting a handle on the unusual complexity of the COVID-19 pandemic.

In this work, we consider two SIR patterns with demography: the classical pattern and a modified pattern with a linear transmission coefficient of the infection. By reformulating of each first order differential systems as a system with two second-order differential equations, we investigate the nonlinear dynamics of the system from the Jacobi stability point of view by using the KCC geometric theory. We will study the intrinsic geometric properties of the systems by determining the geometric associated objects: the zero-connection curvature tensor, the nonlinear connection, the Berwald connection, and the five KCC invariants: the first invariant - the external force εi, the second invariant - the deviation curvature tensor Pji, the third invariant - the torsion tensor Pjki, the fourth invariant - the Riemann-Christoffel curvature tensor Pjkli, and the fifth invariant - the Douglas tensor Djkli. In order to obtain necessary and sufficient conditions for the Jacobi stability near the equilibrium points, the deviation curvature tensor will be determined at each equilibrium points. Furthermore, we will compare the Jacobi stability with the classical linear stability, inclusive by diagrams related to the values of parameters of the system.

The state of epidemic emergency in force in our country since March and the related requirement to implement various sanitary procedures constitute problems for the operation of all companies. However, the unique operation of underground mining companies increases their scale considerably. However, despite initial turbulent moments related to the occurrence of an unknown threat, it was possible to stabilise the situation in all such companies as a result of implementing various anti-threat actions. Following the initial introduction to basic properties of the SARS-CoV-2 coronavirus, the paper presents the results of the study (a case study) on actions taken in individual mining companies. There was an attempt to formulate the so-called good work practices recommended to be applied.

Most popular statistical models in epidemic evolution focus on the dynamics of average relevant quantities and overlooks the role of small fluctuations on the model parameters. Models for Covid-19 are no exception. In this paper we show that the role of time-correlated fluctuations, far from being negligible, can in fact determine the spreading of an epidemic and, most importantly, the resurgence of the exponential diffusion in the presence of time-limited episodes in promiscuity behaviours.

Purpose: This review highlights the global scenario of dengue outbreaks, dengue pathogenesis, symptoms, immune response, diagnosis methods and preventive measures which facilitates the better understanding of the global expansion and concerns relating to the disease. Recent Findings: A recent study showed that natural killer cells of the infected person become activated soon after the infection which may help in treatment and vaccine development. A research team has also produced synthetically engineered mosquitoes that can prevent the transmission and dissemination of the dengue virus by the activation of an antibody. Furthermore, a mutation in the protein envelope of the dengue virus leads to variation in shapes, developing resistance towards the vaccine. Summary: The mosquito vectors marked their worldwide distribution through an increasing number of reported cases which was further facilitated by the growth in the shipping and commerce industries. The immune system, through activation of the innate and adaptive immune responses, facilitates the recruitment of an array of leukocytes which help neutralize the virus. Apart from the laboratory standard PRNT method, several other dengue detection methods such as ELISA, RT-LAMP and several optical, microfluidic and electrochemical methods have been developed. The existence of the 4 different viral serotypes makes the secondary infection life-threatening and also leads to difficulties in vaccine development. Since Dengvaxia® (CYD-TDV) has its own set of drawbacks and limitations, several companies have been investing for the production of more potential vaccines that are currently in trial.

Porcine Circovirus 2 (PCV2) vaccines are based on either inactivated whole virion, or recombinant ORF2 capsid protein assembled into Virus-like Particles (VLPs). No data are available instead about the immunizing properties of free, non-assembled capsid protein. To investigate this issue, ORF2 of a reference PCV2b strain was expressed in a Baculovirus-based expression system without assembly into VLPs. The free purified protein was formulated into an oil vaccine at three distinct Ag payloads: 10.8 / 3.6 / 1.2 micrograms /dose. Each dose was injected intramuscularly into five, 37-day old piglets, carefully matched for maternally-derived antibody. Five control piglets were injected with sterile PBS in oil adjuvant. Twenty-eight days later, all the pigs were challenged intranasally with 200,000 TCID50 of PCV2b strain DV6503. After challenge infection, all the pigs remained in good clinical conditions. The recombinant vaccine did not induce significant antibody and PCV2-specific IFN-gamma responses. ELISPOT and lymphocyte proliferation data confirmed poor induction of cell-mediated immunity. In terms of PCV2 viremia, there was no significant difference between vaccinated and control animals. The histological data indicated the absence of a detectable viral load and of PCVAD lesions in both vaccinated and control animals, as well as of histiocytes and multi-nucleated giant cells. We conclude that free, non-assembled ORF2 capsid protein does not induce protective immunity.

The outbreak of COVID-19 is a public health emergency that caused disastrous results in many countries. The global aim is to stop transmission and prevent the spread of the disease. To achieve it, every country needs to scale up emergency response mechanisms, educate and actively communicate with the public, intensify infected case finding, contact tracing, monitoring, quarantine of contacts, and isolation of cases. Responding to an emergency requires efficient collaboration and a multi-skilled approach (medical, information, statistical, political, social, and other expertise), which makes it hard to define one interface for all. As actors from different perspectives and domain backgrounds need to address diverse functions, the possibility to exchange available information quickly would be desirable. Geoportal provides an entry point to access a variety of data (geospatial data, epidemiological data) and could be used for data discovery, view, download, and transformation. It helps to deal with challenges like data analysis, confirmed cases geocoding, recognition of disease dynamics, vulnerable groups identification, and capacity mapping. Predicting and modeling the spread of infection, along with application support for communication and collaboration, are the biggest challenges. In response to all these challenges, we have established the Epidemic Location Intelligence System (ELIS) using open-source software components in the cloud, as a working platform with all the required functionalities.

The epidemic of Coronavirus Disease 2019 (Covid-19) has brought many changes to people's life. This study aims to analysis Chinese people's psychological change and life after quarantining Wuhan and explore the influencing factors. Based on data from a web-survey after quarantining Wuhan (N=3268), the principal-component-analysis (PCA), multiple-linear-regression (MLR), propensity-score-matching (PSM) were used to explore the psychological change of people in China and the influencing factors. 83.3% of the respondents said that the impact of the epidemic on their life had increased after quarantining Wuhan. A considerable proportion of people's anxiety increased, being reflected in negative emotion, behavioral response and physiological response. The proportion of people who said their anxiety had increased in Wuhan was higher than that in other regions (p <0.05). The anxiety of people who were in medical isolation increased less than those who were not (p <0.05). All three aspects of people’s anxiety were positively related with time of medical isolation and degree of the attention on the epidemic (p＜0.05) except the effect of attention degree on the physiological response (p＝0.06). The measure of medical isolation at home should be advocated. Yet people should reduce the concern for the epidemic while paying attention to self-protection.

This short note proposes a national Geographic Information System (GIS) - based health infrastructure to deal with epidemics and pandemics. Currently, there is no pan-India health infrastructure available that can compile, update, and report the spread of epidemic diseases. It not only curtails the opportunity of finding the real-time data on the spatial distribution of a disease but prevents one to inquire into the causes of the disease through epidemiological analysis. The proposed infrastructure in this study is a pan-India one and can broadly be divided into two parts, hotspot mapping and accessibility to services. In the first part, hospitals are proposed to act as nodes of data collection, sending data to a national GIS portal. This portal shall have the capabilities of plotting the data using map rendering services such as Google and Bing Maps. This way, hotspots can be visualized in no time, benefitting the government and common citizenry alike. The second part deals with the accessibility of citizenry to a wide range of services, i.e., healthcare services, grocery outlets, emergency services, baby food, and many other essential services of the day to day life. In order to implement this, we propose that the government need to enforce a mandatory submission of locational coordinates of all Goods and Services Tax (GST) enrolled service providers. Once the coordinates are submitted, the government can effectively control the opening and closing of services and inform the citizenry at the same time. The proposed infrastructure is going to help deal with the extraordinary situations during epidemic and pandemics similar to what the world is currently facing in the form of Corona Virus Disease 2019 (COVID-19). Furthermore, the infrastructure can be scaled up or down as per the spread of a disease. The health-GIS platform proposed in this concept paper, shall help India in controlling and managing the epidemic more efficiently.