Heterologous Exchanges of Glycoprotein and Non-Virion Protein in Novirhabdoviruses: Assessment of Virulence in Yellow Perch (Perca flavescens) and Rainbow Trout (Oncorhynchus mykiss).

Infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) are rhabdoviruses in two different species belonging to the Novirhabdovirus genus. IHNV has a narrow host range restricted to trout and salmon species, and viruses in the M genogroup of IHNV have high virulence in rainbow trout (Oncorhynchus mykiss). In contrast, the VHSV genotype IVb that invaded the Great Lakes in the United States has a broad host range, with high virulence in yellow perch (Perca flavescens), but not in rainbow trout. By using reverse-genetic systems of IHNV-M and VHSV-IVb strains, we generated six IHNV:VHSV chimeric viruses in which the glycoprotein (G), non-virion-protein (NV), or both G and NV genes of IHNV-M were replaced with the analogous genes from VHSV-IVb, and vice versa. These chimeric viruses were used to challenge groups of rainbow trout and yellow perch. The parental recombinants rIHNV-M and rVHSV-IVb were highly virulent in rainbow trout and yellow perch, respectively. Parental rIHNV-M was avirulent in yellow perch, and chimeric rIHNV carrying G, NV, or G and NV genes from VHSV-IVb remained low in virulence in yellow perch. Similarly, the parental rVHSV-IVb exhibited low virulence in rainbow trout, and chimeric rVHSV with substituted G, NV, or G and NV genes from IHNV-M remained avirulent in rainbow trout. Thus, the G and NV genes of either virus were not sufficient to confer high host-specific virulence when exchanged into a heterologous species genome. Some exchanges of G and/or NV genes caused a loss of host-specific virulence, providing insights into possible roles in viral virulence or fitness, and interactions between viral proteins.

WSV2023 - The second meeting of the world society for virology: One health - One world - One virology.

The Second International Conference of the World Society for Virology (WSV), hosted by Riga Stradins University, was held in Riga, Latvia, on June 15-17th, 2023. It prominently highlighted the recent advancements in different disciplines of virology. The conference had fourteen keynote speakers covering diverse topics, including emerging virus pseudotypes, Zika virus vaccine development, herpesvirus capsid mobility, parvovirus invasion strategies, influenza in animals and birds, West Nile virus and Marburg virus ecology, as well as the latest update in animal vaccines. Discussions further explored SARS-CoV-2 RNA replicons as vaccine candidates, SARS-CoV-2 in humans and animals, and the significance of plant viruses in the 'One Health' paradigm. The presence of the presidents from three virology societies, namely the American, Indian, and Korean Societies for Virology, highlighted the event's significance. Additionally, past president of the American Society for Virology (ASV), formally declared the partnership between ASV and WSV during the conference.

Three-Year Program Evaluation of a University-Public School Collaborative Partnership.

PURPOSE: This clinical focus article reports on an innovative program that provides classroom-based speech and language services to school children receiving speech-language therapy while addressing the need for clinical placements for graduate students in speech-language pathology. This program evaluation report centers around the logic model used to develop and implement the program. METHOD: The program was implemented in partnership between a university program in speech-language pathology and a nearby school district. The program took place in two different schools within the district, each with one state licensed and American Speech-Language-Hearing Association-certified speech-language pathologist (SLP) who supervised two or three graduate student interns per year of the project for a total of 17 graduate students over 3 years. Data sources for this program evaluation included child-level data collected by graduate student interns, teacher satisfaction surveys, and semistructured interviews. RESULTS: Program stakeholders including graduate student interns, speech-language pathology supervisors, and the school district administrator provided converging positive feedback about the program implementation. This was corroborated by favorable ratings from teachers who collaborated with graduate student interns and an increase in the number of classroom-based intervention hours for school children receiving speech-language services. CONCLUSIONS: The short-, medium-, and long-term outcomes of the program's logic model were achieved in part or fully as supported by data sources used for program evaluation procedures. Clinical implications are provided about the need for innovation in school-based services with a focus on collaborative classroom-based intervention.

Identification and characterization of a highly virulent Citrobacter freundii isolate and its activation on immune responses in largemouth bass (Micropterus salmoides).

Citrobacter freundii, a common pathogen of freshwater fish, causes significant commercial losses to the global fish farming industry. In the present study, a highly pathogenic C. freundii strain was isolated and identified from largemouth bass (Micropterus salmoides). The pathogenicity and antibiotic sensitivity of the C. freundii strain were evaluated, and the histopathology and host immune response of largemouth bass infected with C. freundii were investigated. The results showed that C. freundii was the pathogen causing disease outbreaks in largemouth bass, and the infected fish showed typical signs of acute hemorrhages and visceral enlargement. Antimicrobial susceptibility testing showed that the C. freundii strain was resistant to Kanamycin, Medimycin, Clindamycin, Penicillin, Oxacillin, Ampicillin, Cephalexin, Cefazolin, Cefradine and Vancomycin. Histopathological analysis showed different pathological changes in major tissues of diseased fish. In addition, humoral immune factors such as superoxide dismutase (SOD), catalase (CAT) and lysozyme (LZM) were used as serum indicators to evaluate the immune response of largemouth bass after infection. Quantitative real-time PCR (qRT-PCR) was performed to investigate the expression pattern of immune-related genes (CXCR1, IL-8, IRF7, IgM, CD40, IFN-γ, IL-1ß, Hep1, and Hep2) in liver, spleen, and head kidney tissues, which demonstrated a strong immune response induced by C. freundii infection in largemouth bass. The present study provides insights into the pathogenic mechanism of C. freundii and immune response in largemouth bass, promoting the prevention and treatment of diseases caused by C. freundii infection.

Skin-Related Quality of Life During Autoimmune Bullous Disease Course.

Importance: Autoimmune bullous diseases (AIBDs) are chronic relapsing-remitting conditions with significant morbidity. Skin-related quality of life (SRQL) may vary by AIBD subtype and disease type. Disease severity and flare severity can be difficult to define; SRQL can offer a key insight. Objectives: To investigate the Skindex-16 score as an SRQL measure in AIBD subtypes during flare and nonflare states and to evaluate Skindex-16 construct validity. Design, Setting, and Participants: This retrospective cross-sectional study was conducted from September 1, 2016, to February 1, 2020, among 192 patients at the University of Utah Health autoimmune dermatology clinic with pemphigoid, pemphigus, dermatitis herpetiformis, and linear immunoglobulin A disease. Patients had an encounter-associated diagnosis, Skindex-16 scores, and self-reported flare status. Statistical analysis was performed from March 2022 to June 2023. Exposure: Autoimmune bullous disease subtype and patient-reported flare status. Main Outcomes and Measures: Skindex-16 domain scores (emotions, symptoms, and functioning; range, 0-100, where 0 indicates no effect on SRQL and 100 maximum effect) and individual item scores were described by disease and flare status. Flare scores were expected to be higher by at least the standard error of measurement (SEm). Convergent validity was assessed using Spearman correlation among Skindex-16 scores, serologic titers, and other patient-reported outcome measures. Floor or ceiling domain scores (<20% of sample scoring either lowest or highest possible domain scores, respectively) were assessed for Skindex-16. Structural validity was assessed using confirmatory factor analysis (CFA). Results: The study included 192 patients with 212 visits (median age, 68 years [IQR, 58-76 years]; 123 of 212 women [58.0%]) with Skindex-16 scores (64 in flare state and 148 in nonflare state). Median Skindex-16 domain scores were higher for all disease categories among patients in the flare state compared with those in the nonflare state (pemphigoid [emotions: flare, 52.4 (IQR, 38.1-69.0); nonflare, 7 (IQR, 0-17); symptoms: flare, 37.5 (IQR, 29.2-58.0); nonflare, 13 (IQR, 0-25); functioning: flare, 26.7 (IQR, 10.0-56.7); nonflare, 0 (IQR, 0-3)]; pemphigus [emotions: flare, 54.8 (IQR, 31.0-81.0; nonflare, 0 (IQR, 0-19); symptoms: flare, 58.3 (IQR, 41.7-70.8); nonflare, 4 (IQR, 0-12.5); functioning: flare, 26.7 (IQR, 13.3-83.3); nonflare, 0 (IQR, 0-3.33)]; dermatitis herpetiformis [emotions: flare, 72.6 (IQR, 34.7-90.5); nonflare, 14.3 (IQR, 2.4-26.2); symptoms: flare, 69 (IQR, 31.3-85.4); nonflare, 12.5 (IQR, 0-29.2); functioning: flare, 38.3 (IQR, 5.0-63.2); nonflare, 0 (IQR, 0-13.3)]. This difference exceeded SEm cut points. Cronbach α was greater than 0.80 for all domains and AIBDs. Moderate or low correlations were seen with desmoglein 1 and bullous pemphigoid 180 titers. Moderate correlation existed between Skindex-16 and Patient-Reported Outcomes Measurement Information System Depression scores (emotions: ρ = 0.40; symptoms: ρ = 0.41; functioning: ρ = 0.48), and strong correlation existed between Skindex-16 and patient-reported disease severity (emotions: ρ = 0.71; symptoms: ρ = 0.73; functioning: ρ = 0.66). Floor domain scores greater than 20% were seen among patients in the nonflare state, but ceiling domain scores were rare (<10% for all domains); CFA model fit was poor. Conclusions and Relevance: In this cross-sectional study, SRQL was highly associated with flare of AIBDs. Skin-related quality of life was worse during periods without flare among patients with pemphigoid and dermatitis herpetiformis compared with pemphigus, highlighting residual SRQL morbidity. Skindex-16 showed good construct validity, but the poor CFA model fit needs further research. Clinical measurement of SRQL in AIBDs can add critical disease-severity information.

Isolation, identification and the pathogenicity characterization of a Santee-Cooper ranavirus and its activation on immune responses in juvenile largemouth bass (Micropterus salmoides).

The largemouth bass virus (LMBV) isolate of Santee-Cooper ranavirus showed evidence of widespread infection in adult fish, but disease presentation caused by different viral strains exhibited considerable difference. In this study, a highly pathogenic LMBV-like resembling Santee-Cooper ranavirus was isolated and identified from juvenile largemouth bass. The pathogenicity and dynamic distribution of LMBV-like strain, histopathological analysis and host immune response of juvenile largemouth bass infected with LMBV-like were investigated. The results show that LMBV-like was highly pathogenic to juvenile fish, and the infected fish showed typical signs of acute haemorrhages and visceral enlargement. LMBV-like positive cells were found in the liver, spleen, kidney, gills, and intestinal tissue, and the virus content in spleen was the highest. Histopathological analysis showed different pathological changes in major tissues of diseased fish, mostly manifested as infiltration of inflammatory cell and histiocyte necrosis. In addition, humoral immune factors such as superoxide dismutase (SOD), catalase (CAT) and acid phosphatase (ACP) were used as serum indicators to evaluate the immune response of juvenile fish after infection. Quantitative real-time PCR (qRT-PCR) was used to evaluate the expression patterns of immune-related genes (CD40, IFN-γ, IgM, IL-1ß, IL-8, IL-12a, Mxd3, TGF-ß, and TNFα) in liver, spleen, and head kidney tissues. The results showed that immunological activity of the juvenile largemouth bass was significantly enhanced by LMBV-like infection. This research comprehensively systematically revealed the pathogenic characteristics of LMBV-like separated from juvenile largemouth bass and properties of the host's immune response caused by the virus infection, which providing a basis for further exploring the interaction between the virus and the host, and prevention and treatment of disease caused by Santee-Cooper ranavirus.

Mycophenolate mofetil-induced hyperlipidemia with cutaneous manifestations.

We report a case of a 49 year old woman who developed biopsy-proven xanthomas on her hands and arms after initiation of Mycophenolate mofetil therapy for systemic lupus erythematosus (SLE) and subsequently went into remission upon cessation of the medication.

The efficacy of new oral vaccine feeds against Salmonid novirhabdovirus in rainbow trout.

Salmonid novirhabdovirus (IHNV) causes infectious haematopoietic necrosis (IHN) in salmonid species. Despite an injectable plasmid-based DNA vaccine of the glycoprotein (G) gene is effective, there are no oral vaccines for mass vaccination of rainbow trout (Oncorhynchus mykiss) fry. Recombinant baculoviruses were generated, used in cabbage looper (Trichoplusia ni) insect larvae to produce IHNV G and IHNV G-C5a proteins. Western blotting and chemiluminescence assays confirmed the expression of recombinant proteins, which were added to the fish feeding and top-coated with unflavored gelatin binder. Commercial rainbow trout were fed with experimental diets containing either IHNV G or IHNV G-C5a proteins for 2 weeks, and boosted 4 weeks after. Four weeks post-booster, fish were challenged with IHNV by immersion. Survival upon the infection challenge was evaluated. Spleen were sampled at 7 and 14 days post infection (dpi). Non-vaccinated and IHNV G fed trout reached a mortality of 91.7 and 97.6%, and 70.9 and 88.4%, respectively at 8 and 15 dpi. The IHNV G-C5a fed group exhibited a reduced mortality of 51.2% at 8 dpi, reaching 81.7% at 15 dpi, suggesting some level of antiviral protection. The individual viral load was measured by RT-qPCR detection of IHNV N gene, showing no significant difference across experimental groups. The transcription modulation of selected immune response markers was evaluated across experimental groups, including Type I IFN-a, Mx-1, CD4, and IgM. Further study is needed to assess how new oral vaccines may become effective to mitigate IHNV pathogenesis in juvenile trout by modulating the host immune response to protect towards IHNV exposure.

Beyond Competency: A Student Perspective on Growth Through Clerkship Feedback.

This article proposes a paradigm shift from the competency-based model of clerkship feedback using checklists to a coaching-based, action plan-oriented process that centers on individualized student-oriented goals. Using a student perspective, the authors examine the feedback literature and put forward a proposal to use an impact model whose emphasis is to improve the learning climate for students. Several techniques are reviewed which include goal generation and creation of dynamic action plans. By intentionally focusing on coaching relationships as a platform for feedback, the learners and mentors share goals and the result of feedback becomes action-based behaviors which may help negate personal attribution and bias in the feedback process.

Screening of genes encoding proteins that interact with ISG15: Probing a cDNA library from a snakehead fish cell line using a yeast two-hybrid system.

Interferon-stimulated gene 15 (ISG15) regulates cellular life processes, including defense responses against infection by a variety of viral pathogens, by binding to target proteins. At present, various fish ISG15s have been identified, but the biological function of ISG15 in snakehead fish is still unclear. In this study, total RNA was extracted from snakehead fish cell line E11, ds cDNA was synthesized and purified using SMART technology, and the resulting cDNA library was screened by co-transforming yeast cells. The library titer was 4.28 × 109 CFU/mL. Using snakehead ISG15 as the bait protein, the recombinant bait vector pGBKT7-ISG15 was constructed and transformed into the yeast strain Y2HGold. The toxicity and self-activation activity of the bait vector were detected on the deficient medium, and the prey proteins interacting with ISG15 were screened. In total, 19 interacting proteins of ISG15 were identified, including mitotic checkpoint protein BUB3, hypothetical protein SnRVgp6, elongation factor 1-beta, 60S ribosomal protein L9, dual specificity protein phosphatase 5-like, eukaryotic translation initiation factor 3 subunit I and ferritin. A yeast spotting assay further probed the interaction between ISG15 and DUSP5. These results increase our understanding of the interaction network of snakehead ISG15 and will aid in exploring the underlying mechanisms of snakehead ISG15 functions in the future.

Genetic subtyping and phylogenetic analysis of HA and NA from avian influenza virus in wild birds from Peru reveals unique features among circulating strains in America.

Avian influenza virus (AIV) represents a major concern with productive implications in poultry systems but it is also a zoonotic agent that possesses an intrinsic pandemic risk. AIV is an enveloped, negative-sense and single-stranded RNA virus with a segmented genome. The eight genomic segments, comprising the whole genome, encode for eleven proteins. Within these proteins, Hemagglutinin (HA) and Neuraminidase (NA) are the most relevant for studies of evolution and pathogenesis considering their role in viral replication, and have also been used for classification purposes. Migratory birds are the main hosts and play a pivotal role in viral evolution and dissemination due to their migratory routes that comprise large regions worldwide. Altogether, viral and reservoir factors contribute to the emergence of avian influenza viruses with novel features and pathogenic potentials. The study aimed to conduct surveillance of AIVs in wild birds from Peru. A multi-site screening of feces of migratory birds was performed to isolate viruses and to characterize the whole genome sequences, especially the genes coding for HA and NA proteins. Four-hundred-twenty-one (421) fecal samples, collected between March 2019 and March 2020 in Lima, were obtained from 21 species of wild birds. From these, we isolated five AIV from whimbrel, kelp gull, Franklin's gulls and Mallard, which were of low pathogenicity, including four subtypes as H6N8, H13N6, H6N2 and H2N6. Genetic analysis of HA and NA genes revealed novel features in these viruses and phylogenetic analysis exhibited a close relationship with those identified in North America (US and Canada). Furthermore, H2N6 isolate presented a NA sequence with higher genetic relationship to Chilean isolates. These results highlight that the geographical factor is of major relevance in the evolution of AIV, suggesting that AIV circulating in Peru might represent a new site for the emergence of reassortant AIVs.

Intranasal vaccination of hamsters with a Newcastle disease virus vector expressing the S1 subunit protects animals against SARS-CoV-2 disease.

The coronavirus disease-19 (COVID-19) pandemic has already claimed millions of lives and remains one of the major catastrophes in the recorded history. While mitigation and control strategies provide short term solutions, vaccines play critical roles in long term control of the disease. Recent emergence of potentially vaccine-resistant and novel variants necessitated testing and deployment of novel technologies that are safe, effective, stable, easy to administer, and inexpensive to produce. Here we developed three recombinant Newcastle disease virus (rNDV) vectored vaccines and assessed their immunogenicity, safety, and protective efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice and hamsters. Intranasal administration of rNDV-based vaccine candidates elicited high levels of neutralizing antibodies. Importantly, the nasally administrated vaccine prevented lung damage, and significantly reduced viral load in the respiratory tract of vaccinated animal which was compounded by profound humoral immune responses. Taken together, the presented NDV-based vaccine candidates fully protected animals against SARS-CoV-2 challenge and warrants evaluation in a Phase I human clinical trial as a promising tool in the fight against COVID-19.

In vitro anti-inflammatory activity of silymarin/hydroxyapatite/chitosan nanocomposites and its cytotoxic effect using brine shrimp lethality assay.

Silymarin, a bioactive compound, is one of the most prominent drugs used in liver diseases. Chitosan and hydroxyapatite (HAP) are the major materials used employed in many biomedical processes like drug delivery, osteointegration, etc. The nanoparticles and nanocomposites are advanced materials with many biomedical applications in diagnosis and therapeutics. In this study, HAP and chitosan were used as a polymeric material, silymarin as a bioactive compound, and other nanoparticle based combinations. The prepared individual materials and nanocomposites were used for the anti-inflammatory activity and brine shrimp lethality assay. The results clearly show that the nanocomposites are good anti-inflammatory agents with lower toxicity.

Efficacy of Fluoride Varnish with Casein Phosphopeptide and Amorphous Calcium Phosphate vs Fluoride Varnish in Prevention of White Spots Lesion in fixed Orthodontic Patients: In Vivo Study.

AIM: The aim of the study is to compare the in vivo efficiency of Michigan (MI) varnish containing casein phosphopeptide (CPP) and amorphous calcium phosphate (ACP) and Fluoritop containing sodium fluoride (5% NaF) in the prevention and remineralization of white spot lesions (WSLs) around orthodontic brackets at days 28 and 56 after bonding. MATERIALS AND METHODS: A total of 30 patients were selected and divided into two groups I (MI varnish) II (Fluoritop varnish) of 15 patients in each group. All the patients were bonded and then varnish was applied around the brackets. Right-side upper and lower first premolar teeth were taken as the control group and left-side upper and lower first premolar teeth as the experimental group. Also, 14, 24 teeth were extracted on day 28 after bonding and 34, 44 teeth after day 56 of bonding. Samples were collected and sent to laboratory for evaluation of surface microhardness (SMH). RESULTS: Based on the statistics results, there was a significant decrease in demineralization and an increase in remineralization of WSLs after the application of varnish. No statistical significance was found between the effectiveness of MI varnish and Fluoritop except in the cervical region. CONCLUSION: Through our study, we concluded that no statistical significance was found between the effectiveness of MI varnish and Fluoritop except in the cervical region where MI varnish was found to be more effective than Fluoritop in preventing WSLs. CLINICAL SIGNIFICANCE: The results from the above study concluded that CPP-ACP varnish can be an effective method in preventing WSLs in patients undergoing fixed orthodontic treatment.

The evolving atopic dermatitis management landscape.

INTRODUCTION: Atopic dermatitis is a common dermatologic condition that affects millions of people worldwide, and a standardized approach to treatment was published by the American Academy of Dermatology (AAD) in 2013-14. Since 2014, new FDA-approved treatment options such as dupilumab and crisaborole have changed the landscape of AD management, and future therapies such as JAK inhibitors and anti-interleukin 13 and 31 antibodies appear effective, emphasizing the need for a comprehensive review to give clinicians an updated toolbox to aid in pharmacologic management. AREAS COVERED: In this review, the authors explore the updated efficacy and safety data on established therapeutic options for AD including topical corticosteroids, topical calcineurin inhibitors, cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil. In addition, the authors also explore trial data and studies on dupilumab, crisaborole, omalizumab, tofacitinib, ruxolinitib, abrocitinib, baricitinib, upadacitinib, delgocitinib, nemoliuzumab, and tralokinumab. EXPERT OPINION: The AAD guidelines must be updated in the future to include several new treatment modalities that have revolutionized the pharmacologic management of patients with AD, including dupilumab and crisaborole. The future of AD treatment is also extremely bright, as JAK inhibitors and Il-13/31 antibodies have shown convincing results in the improvement of AD patients' lives in various trials and studies that have been examined in this paper.

World Society for Virology first international conference: Tackling global virus epidemics.

This communication summarizes the presentations given at the 1st international conference of the World Society for Virology (WSV) held virtually during 16-18 June 2021, under the theme of tackling global viral epidemics. The purpose of this biennial meeting is to foster international collaborations and address important viral epidemics in different hosts. The first day included two sessions exclusively on SARS-CoV-2 and COVID-19. The other two days included one plenary and three parallel sessions each. Last not least, 16 sessions covered 140 on-demand submitted talks. In total, 270 scientists from 49 countries attended the meeting, including 40 invited keynote speakers.

Disseminate and Recurrent Infundibulofolliculitis: An Under-Recognized Yet Treatable Entity.

Disseminate and recurrent infundibulofolliculitis (DRIF) is a pruritic papular eruption that predominantly affects young adults with Fitzpatrick skin types 4-6. Due to DRIF’s rarity and under-recognition, no standardized treatment guidelines exist. However, several oral agents have been used, including vitamin A, antibiotics, and retinoids. Topical agents, such as calcineurin inhibitors and mid-potency steroids, can also be efficacious. This brief communication summarizes treatments for DRIF in the published literature. J Drugs Dermatol. 2021;20(12):1353-1354. doi:10.36849/JDD.6173.

Bullous Pemphigoid and Other Pemphigoid Dermatoses.

The pemphigoid family of dermatoses is characterized by autoimmune subepidermal blistering. The classic paradigm for pemphigoid, and the most common member, is bullous pemphigoid. Its variable clinical presentation, with or without frank bullae, is linked by significant pruritus afflicting the elderly. Mucous membrane pemphigoid is an umbrella term for a group of subepidermal blistering dermatoses that favor the mucosal membranes and can scar. Epidermolysis bullosa acquisita is a chronic blistering disorder characterized by skin fragility, sensitivity to trauma, and its treatment-refractory nature. Clinicians that encounter these pemphigoid disorders may benefit from an overview of their clinical presentation, diagnostic work-up, and therapeutic management, with an emphasis on the most frequently encountered pemphigoid disease, bullous pemphigoid.