Characterizing the splice map of Turkey Hemorrhagic Enteritis Virus.

BACKGROUND: Hemorrhagic enteritis, caused by Turkey Hemorrhagic Enteritis Virus (THEV), is a disease affecting turkey poults characterized by immunosuppression and bloody diarrhea. An avirulent THEV strain that retains the immunosuppressive ability is used as a live vaccine. Characterizing the splice map of THEV is an essential step that would allow studies of individual genes mediating its immunosuppressive functions. We used RNA sequencing to characterize the splice map of THEV for the first time, providing key insights into the THEV gene expression and mRNA structures. METHODS: After infecting a turkey B-cell line with the vaccine strain, samples in triplicates were collected at 4-, 12-, 24-, and 72-hours post-infection. Total RNA was extracted, and poly-A-tailed mRNA sequenced. Reads were mapped to the THEV genome after trimming and transcripts assembled with StringTie. We performed PCR of THEV cDNA, cloned the PCR products, and used Sanger sequencing to validate all identified splice junctions. RESULTS: Researchers previously annotated the THEV genome as encoding 23 open reading frames (ORFs). We identified 29 spliced transcripts from our RNA sequencing data, all containing novel exons although some exons matched some previously annotated ORFs. The three annotated splice junctions were also corroborated by our data. During validation we identified five additional unique transcripts, a subset of which were further validated by 3' rapid amplification of cDNA ends (3' RACE). Thus, we report that the genome of THEV contains 34 transcripts with the coding capacity for all annotated ORFs. However, we found six of the previously annotated ORFs to be truncated ORFs on the basis of the identification of an in-frame upstream start codon or the detection of additional coding exons. We also identified three of the annotated ORFs with longer or shorter isoforms, and seven novel unannotated ORFs that could potentially be translated; although it is beyond the scope of this manuscript to investigate whether they are translated. CONCLUSIONS: Similar to human adenoviruses, all THEV transcripts are spliced and organized into five transcription units under the control of their cognate promoters. The genes are expressed under temporal regulation and THEV also produces multiple distinctly spliced transcripts that code for the same protein. Studies of the newly identified potential proteins should be urgently performed as these proteins may have roles in THEV-induced immunosuppression. Also, knowing the splicing of THEV genes should be invaluable to future research focusing on studying THEV genes, as this will allow accurate cloning of the mRNAs.

Changes in Attitudes and Barriers to Seasonal Influenza Vaccination from 2007 to 2023.

This study investigated how factors and barriers to flu vaccination among college students has changed over the past 16 years. Data were collected from 440 students using a survey and compared to previous data from the same university. Respondents were also asked about their experiences with Covid-19 and its effect on their intent to vaccinate. We found that vaccination rates had increased from 12.4 to 30.5%. Among the unvaccinated, expense, fear of getting influenza from vaccination, fear of side effects, and lack of information have decreased by 28%, 20%, 17%, and 15% respectively. Time, convenience, and perceived risk are still significant barriers to vaccination. Students are getting more encouragement to vaccinate from their health care providers and parents, but it is becoming less effective. The Covid-19 pandemic has changed vaccine attitudes and vaccine fatigue has been a large contributor. Additionally, political affiliation has become a predictor of flu vaccine uptake with conservatives being less likely to vaccinate. There has also been a shift in motivation from concern for personal safety to concern for public safety.

A Randomized Study to Determine the Effect of a Culturally Focused Video Intervention on Improving HPV Vaccine Intentions in a Christian Population in the United States.

Safe and effective vaccines have been developed that protect against high-risk strains of HPV, but uptake is relatively low. We previously identified factors such as sexual attitudes and HPV knowledge that impact the intent of Christian parents to vaccinate their children against HPV. We hypothesized that culturally specific interventions in the form of short videos would be effective at improving HPV vaccine intentions and attitudes. We made three short educational videos, one with a Christian focus, one informational about HPV, and one control. Videos were distributed electronically with accompanying surveys, and responses were measured before and after watching a randomly selected video. The religious-focused and educational interventions significantly (p < 0.0001, p = 0.0015) improved intentions towards HPV vaccination. The religiously-focused video also significantly diminished the belief that the HPV vaccine is unnecessary because of a family's values (p = 0.014). Parents significantly credited both interventions with improving their intent to vaccinate their children against HPV (p < 0.001 for both). These results suggest that culturally focused educational interventions are effective at influencing vaccine intentions and attitudes, even when those are based on religious or cultural feelings. Highly specific interventions are likely to be necessary for optimal improvement in vaccine hesitancy.

Synthetic Pharmacotherapy for Systemic Lupus Erythematosus: Potential Mechanisms of Action, Efficacy, and Safety.

The pharmacological treatment of systemic lupus erythematosus (SLE) aims to decrease disease activity, progression, systemic compromise, and mortality. Among the pharmacological alternatives, there are chemically synthesized drugs whose efficacy has been evaluated, but which have the potential to generate adverse events that may compromise adherence and response to treatment. Therapy selection and monitoring will depend on patient characteristics and the safety profile of each drug. The aim of this review is to provide a comprehensive understanding of the most important synthetic drugs used in the treatment of SLE, including the current treatment options (mycophenolate mofetil, azathioprine, and cyclophosphamide), review their mechanism of action, efficacy, safety, and, most importantly, provide monitoring parameters that should be considered while the patient is receiving the pharmacotherapy.

EBI2 expression in B lymphocytes is controlled by the Epstein-Barr virus transcription factor, BRRF1 (Na), during viral infection.

Epstein-Barr virus-induced gene 2 (EBI2) is an important chemotactic receptor that is involved in proper B-cell T-cell interactions. Epstein-Barr virus (EBV) has been shown to upregulate this gene upon infection of cell lines, but the timing and mechanism of this upregulation, as well as its importance to EBV infection, remain unknown. This work investigated EBV's manipulation of EBI2 expression of primary naive B cells. EBV infection induces EBI2 expression resulting in elevated levels of EBI2 after 24 h until 7 days post-infection, followed by a dramatic decline (P=0.027). Increased EBI2 expression was not found in non-specifically stimulated B cells or when irradiated virus was used. The EBV lytic gene BRRF1 exhibited a similar expression pattern to EBI2 (R2=0.4622). BRRF1-deficient EBV could not induce EBI2. However, B cells transduced with BRRF1 showed elevated expression of EBI2 (P=0.042), a result that was not seen with transduction of a different EBV lytic transfection factor, BRLF1. Based on these results, we conclude that EBI2 expression is directly influenced by EBV infection and that BRRF1 is necessary and sufficient for EBI2 upregulation during infection.

Piracy on the molecular level: human herpesviruses manipulate cellular chemotaxis.

Cellular chemotaxis is important to tissue homeostasis and proper development. Human herpesvirus species influence cellular chemotaxis by regulating cellular chemokines and chemokine receptors. Herpesviruses also express various viral chemokines and chemokine receptors during infection. These changes to chemokine concentrations and receptor availability assist in the pathogenesis of herpesviruses and contribute to a variety of diseases and malignancies. By interfering with the positioning of host cells during herpesvirus infection, viral spread is assisted, latency can be established and the immune system is prevented from eradicating viral infection.

Effects of religious and cultural beliefs on vaccine attitudes in a Hispanic immigrant population in the United States.

Hispanic Immigrants (HI) have lower vaccination rates than their non-Hispanic white counterparts. Culturally appropriate interventions are more influential in evoking change among viewers; therefore, it is important to understand the cultural factors of specific ethnic groups. In this study, we identify cultural barriers to vaccination of Hispanic Immigrants. An electronic survey was administered among HI parents living in the United States. Using structural equation modeling, we found that high religious practice and positive religious beliefs towards vaccination correspond with positive vaccine attitudes (+0.20 and +0.587, respectively). Trust in institutions is strongly correlated with strong positive vaccine attitudes (+0.734). While trusting one's folk practitioner more than a medical doctor leads to negative vaccine attitudes (-0.596), the use of home remedies is associated with positive vaccine attitudes (+0.486). The cultural competence of a medical practitioner, especially regarding folk medicine, is essential to lower cultural barriers HI patients face in vaccination.

Cytokine inhibition as a strategy for treating systemic lupus erythematosus.

Cytokines regulate and control the immune system. In systemic lupus erythematosus, several of these cytokines are overexpressed and contribute to the pathogenesis of the disease. Cytokine inhibition has been successfully used to treat other rheumatic and autoimmune diseases, and several cytokines are currently being investigated to determine whether inhibition would be therapeutic in lupus. The cytokines discussed in this review have all undergone clinical trials, and include TNF-α, IL-1, IL-6, IL-10, IL-15, IL-17, IL-18 and IL-23. Inhibition of the majority of these targets was safe and showed some efficacy in treating lupus. Cytokine inhibition strategies have just started to realize their potential for the treatment of this difficult disease, and show great promise for the future.

Association between Religious Beliefs and HPV Vaccination Attitudes among College Students.

OBJECTIVE AND PARTICIPANTS: The authors sought an updated examination of attitudes toward Human Papillomavirus (HPV) catch-up vaccination among college students at a private religious university. METHODS: A total of 1557 college students completed a 62-question survey of religious and HPV vaccination attitudes during the fall of 2021. Students' willingness to receive catch-up HPV vaccination and willingness to vaccinate a future child against HPV were recorded. RESULTS: Of the 46.8% of students who reported being unvaccinated or unaware of vaccination status, ~26% reported being uninterested in receiving catch-up HPV vaccination; ~22% of all students surveyed reported being unwilling to vaccinate a future child against HPV. The strongest predictors of vaccine hesitancy included religious concerns about sexual abstinence and safety concerns. CONCLUSIONS: College health professionals can increase the rate of HPV vaccination among college students and subsequent future generations by addressing the safety and utility of the vaccine regardless of intentions for sexual abstinence prior to marriage. Additionally, rather than a uniform approach to all students who self-identify as Christian, an effort to identify and discuss the unique religiously influenced beliefs of individual students is recommended when discussing HPV vaccination.

A Novel Application of Spinning Disk Technology to Collect Plasma from Whole Blood Prior to Quantifying Plasma RNA.

The spinning disk technology has previously been utilized to isolate bacterial components from blood in hours instead of days. We hypothesized that this platform could be applied as an alternative approach to isolating plasma RNA from a whole blood sample. We consequently tested the efficacy of the spinning disk technology to extract plasma from whole blood upstream of RNA isolation and analysis. To do so, we collected plasma using either the spinning disk or the typical two-spin centrifuge method. We found that the spinning disk method results in significantly more hemolysis during collection than the conventional two-spin centrifuge method. However, when plasma RNA recovered from both collection methods was quantified using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), we found that the spinning disk method yielded a higher plasma RNA concentration than the two-spin centrifuge method. This suggests that the spinning disk may be an efficient alternative method to recover plasma RNA. Further work is needed to determine whether red blood cell RNA contamination is present in the plasma RNA extracted from spinning disk-processed plasma.

Factors Affecting Vaccine Attitudes Influenced by the COVID-19 Pandemic.

The development of vaccines has significantly contributed to the success of disease prevention. However, there has been a sharp decline in immunization rates since COVID-19 spread globally. Seemingly overnight, the world shut down and most non-essential medical procedures were postponed. Since the COVID-19 vaccine became available, and the world started going back to normal these vaccine rates have not recovered. In this paper, we review the published literature to explore how convenience factors, perceived risk of vaccination, media or anti-vaccination ideals/movements, and healthcare professionals affect an individual's compliance to be vaccinated to better understand the factors that contribute to the change in overall vaccination rates.

Decrease in Overall Vaccine Hesitancy in College Students during the COVID-19 Pandemic.

The COVID-19 pandemic changed our world as we know it and continues to be a global problem three years since the pandemic began. Several vaccines were produced, but there was a considerable amount of societal turmoil surrounding them that has affected the way people view not only COVID-19 vaccines but all vaccines. We used a survey to compare how attitudes towards vaccination have changed in college students during the pandemic. An initial survey was administered in 2021, then a follow-up in 2022. Out of 316 respondents who answered the first survey, 192 completed the follow-up. The survey was designed to measure trends in changes to vaccine attitudes since the COVID-19 pandemic began. By comparing the first survey in 2021 and the follow-up, we found that roughly 55% of respondents' vaccine attitudes did not change, roughly 44% of respondents' attitudes towards vaccines became more positive, and only about 1% of the respondents' vaccine attitudes became more negative. Improved view of vaccines was associated with political views and increased trust in medicine and the healthcare system. Worsened opinions of vaccines were associated with a belief that the COVID-19 vaccine affected fertility.

Effects of IRF5 lupus risk haplotype on pathways predicted to influence B cell functions.

Both genetic and environmental interactions affect systemic lupus erythematosus (SLE) development and pathogenesis. One known genetic factor associated with lupus is a haplotype of the interferon regulatory factor 5 (IRF5) gene. Analysis of global gene expression microarray data using gene set enrichment analysis identified multiple interferon- and inflammation-related gene sets significantly overrepresented in cells with the risk haplotype. Pathway analysis using expressed genes from the significant gene sets impacted by the IRF5 risk haplotype confirmed significant correlation with the interferon pathway, Toll-like receptor pathway, and the B-cell receptor pathway. SLE patients with the IRF5 risk haplotype have a heightened interferon signature, even in an unstimulated state (P = 0.011), while patients with the IRF5 protective haplotype have a B cell interferon signature similar to that of controls. These results identify multiple genes in functionally significant pathways which are affected by IRF5 genotype. They also establish the IRF5 risk haplotype as a key determinant of not only the interferon response, but also other B-cell pathways involved in SLE.

Influences on Attitudes Regarding COVID-19 Vaccination in Germany.

Trust in institutions and democracy may be a major contributor to the willingness to be vaccinated. We investigated these factors and others with regard to COVID-19 vaccine uptake in Germany. Even though effective vaccination is a major contributor to slowing down the current pandemic, vaccine hesitancy remains a major challenge. To analyze attitudes toward vaccine hesitancy, a web-based cross-sectional survey was used to understand and describe the influences of attitudes about vaccination against COVID-19 in the German population. A descriptive analysis for the entire dataset was carried out, and multiple proportional odds regression, path model, and structural equation modeling (SEM) were subsequently used to analyze any relationship between latent variables and COVID-19 vaccine acceptance. In total, 1092 responses from across Germany were analyzed. SEM modeling revealed that trust in institutions, trust in non-pharmaceutical interventions, and various demographic factors were associated with intent to vaccinate. Descriptive analysis and multiple proportional odds regression confirmed that a history of influenza vaccination and level of satisfaction with democratic institutions were highly predictive (p < 0.05) for COVID-19 vaccine acceptance. Additionally, social determinants of health such as gender, age, number of children in the family, and the degree of satisfaction with life were also predictors (p < 0.05) for COVID-19 vaccine acceptance. Results also demonstrated a significant relationship between receiving the flu vaccine and acceptance of the COVID-19 vaccination. Governments that provide COVID-19 vaccines and control messaging should strive for trust and transparency to maximize vaccine uptake. Government-based vaccine measures should also involve measures to communicate trust in democratic and scientific institutions.

Cautious Sexual Attitudes Diminish Intent to Vaccinate Children against HPV in Utah.

Although most Human papillomavirus (HPV) infections are mild and are cleared by the immune system, some high-risk HPV strains can cause various cancers. Vaccines have been developed that protect against high-risk HPV strains. HPV vaccines have been approved for use by the CDC (Centers for Disease Control and Prevention) and are recommended for everyone aged 11-26. Despite the availability of safe and effective vaccines, uptake is low. HPV vaccine uptake has been extensively studied on a national and international level, but less is known about vaccine acceptance on a state or local level. The state of Utah, in the United States of America, has a relatively low HPV vaccination rate. In this study, we identified factors that impact the intent of Utah parents to vaccinate their children against HPV. A survey was distributed electronically to Utah residents. Survey results were analyzed using confirmatory factor analysis, structural equation modeling, and univariate analysis. Knowledge about HPV and positive vaccine attitudes had the greatest positive effect on intent to vaccinate children against HPV. Cautious sexual attitudes and high religious practice were found to have a negative impact on intent to vaccinate. Effective public health messaging will consider the cultural and religious influences of the target population.

Effects of Religious Practice and Teachings about Sexual Behavior on Intent to Vaccinate against Human Papillomavirus.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Most infections are mild and clear without treatment in 1 to 2 years. Some HPV strains result in persistent infection, which can cause various cancers, including cervical, penile, anal, mouth, and throat cancers. Vaccines have been developed that provide protection against the highest risk HPV strains. Despite HPV vaccines having been proven to be safe and effective, uptake has been low. Religiosity has been negatively correlated with HPV vaccine uptake in some studies. It is hypothesized that religiosity and Christian religious affiliation could impact parents' decision to vaccinate their children against HPV via teachings and beliefs about sexual behaviors. A survey was distributed to participants to determine what factors, including religiosity and views about sex, impacted HPV vaccination. The survey results (n = 442) were analyzed using confirmatory factor analysis, structural equation modeling, and univariate factor analysis. The association between religious practice and vaccine attitudes were complex, with religious practice slightly positively correlated with pro-vaccine attitudes and vaccine knowledge, but also with the belief that religious adherence to expectations surrounding sexual behavior will protect children from HPV infection, as well as more negative views towards vaccines, in general.

Impact of Local and Demographic Factors on Early COVID-19 Vaccine Hesitancy among Health Care Workers in New York City Public Hospitals.

Despite the development of several effective vaccines, SARS-CoV-2 continues to spread, causing serious illness among the unvaccinated. Healthcare professionals are trusted sources of information about vaccination, and therefore understanding the attitudes and beliefs of healthcare professionals regarding the vaccines is of utmost importance. We conducted a survey-based study to understand the factors affecting COVID-19 vaccine attitudes among health care professionals in NYC Health and Hospitals, at a time when the vaccine was new, and received 3759 responses. Machine learning and chi-square analyses were applied to determine the factors most predictive of vaccine hesitancy. Demographic factors, education, role at the hospital, perceptions of the pandemic itself, and location of work and residence were all found to significantly contribute to vaccine attitudes. Location of residence was examined for both borough and neighborhood, and was found to have a significant impact on vaccine receptivity. Interestingly, this borough-level data did not correspond to the number or severity of cases in the respective boroughs, indicating that local social or other influences likely have a substantial impact. Local and demographic factors should be strongly considered when preparing pro-vaccine messages or campaigns.

Characterization of herpes simplex virus clinical isolate Y3369 as a glycoprotein G variant and its bearing on virus typing.

BACKGROUND: Herpes simplex viruses exist as two major serotypes, type 1 (HSV-1) and type 2 (HSV-2). Determination of type, either HSV-1 or HSV-2, is important in accurate diagnosis and clinical control of transmission. Several tests are available for typing HSV, including a monoclonal antibody specific for glycoprotein G and several PCR assays. FINDINGS: A clinical isolate was identified as herpes simplex virus, but tested negative for both HSV-1 and HSV-2 antigens using type-specific monoclonal antibody assays. The isolate was determined to be HSV-1 by PCR analysis. A mutation which likely caused the monoclonal antibody non-reactivity was found in glycoprotein G. Phylogenetic analysis revealed two groups of HSV, one with the mutation and one without. Three population studies examining mutations in HSV-1 glycoprotein G were analyzed by chi-squared test. To this point, the epitope which the monoclonal antibody recognizes was only found in HSV-1 isolates from human European populations (p < 0.0001). CONCLUSIONS: These findings suggest that the PCR-based methods for HSV typing may be more useful than the standard monoclonal antibody test in areas of the world where the variant in glycoprotein G is more prevalent.

Parvovirus B19 nonstructural protein-induced damage of cellular DNA and resultant apoptosis.

Parvovirus B19 is a widespread virus with diverse clinical presentations. The viral nonstructural protein, NS1, binds to and cleaves the viral genome, and induces apoptosis when transfected into nonpermissive cells, such as hepatocytes. We hypothesized that the cytotoxicity of NS1 in such cells results from chromosomal DNA damage caused by the DNA-nicking and DNA-attaching activities of NS1. Upon testing this hypothesis, we found that NS1 covalently binds to cellular DNA and is modified by PARP, an enzyme involved in repairing single-stranded DNA nicks. We furthermore discovered that the DNA nick repair pathway initiated by poly(ADPribose)polymerase and the DNA repair pathways initiated by ATM/ATR are necessary for efficient apoptosis resulting from NS1 expression.

Kidney Function, Age, and Education as Contributors to Depression and Anxiety in Juvenile Systemic Lupus Erythematosus.

Juvenile systemic lupus erythematosus (JSLE) is diagnosed in children younger than 18 years of age. Depression and anxiety are common, but not well understood in JSLE. We investigated the clinical and psychological factors associated with the psychological manifestations of JSLE. Twenty-nine JSLE patients were recruited for the study. Patients completed surveys evaluating their psychological status and perceptions about their health. Medical records were used to obtain laboratory results. The JSLE patient population was compared with adult-onset SLE (ASLE) patients and unaffected controls. Kidney involvement was associated with depression in the JSLE patients. The BUN levels, BUN/creatinine ratio, and leukocyturia were all significantly associated with depressive symptoms. Multivariate analysis found that the BUN/creatinine ratio was the most predictive value for both depression and anxiety. Depressive symptoms in JSLE were less pronounced than in ASLE, although anxiety was not different. Age and education are likely to be protective against depression in the JSLE patients. These findings may indicate that symptomatology is an important indicator of whether the patient needs psychiatric care.