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The American Journal of Case Reports Jun 2024BACKGROUND Parinaud oculoglandular syndrome is a unilateral granulomatous palpebral conjunctivitis associated with preauricular, submandibular, and cervical...
BACKGROUND Parinaud oculoglandular syndrome is a unilateral granulomatous palpebral conjunctivitis associated with preauricular, submandibular, and cervical lymphadenopathies. Several infectious diseases can cause Parinaud oculoglandular syndrome, usually with a conjunctival entry. The most common underlying pathology is cat scratch disease, followed by the oculoglandular form of tularemia. Diagnosis is usually a serious challenge as these infections are themselves rare. On the other hand, Parinaud oculoglandular syndrome may be a rare manifestation of more common disorders (eg, tuberculosis, syphilis, mumps, herpes simplex and Epstein-Barr virus, adenovirus, Rickettsia, Sporothrix, Chlamydia infections). CASE REPORT We present the case of a 66-year-old man with granulomatous conjunctivitis and ipsilateral preauricular, submandibular, and upper cervical lymphadenopathies following a superficial corneal injury. Although the systematic amoxicillin/clavulanic acid and metronidazole antibiotic therapy started immediately at admission, the suppuration of the lymph nodes required surgical drainage. Based on his anamnesis (sheep breeding; a twig scratching his eye 2 days before the initial attendance) and symptoms, a zoonosis, namely the oculoglandular form of tularemia, was suspected, empiric ciprofloxacin therapy was administered, and the patient recovered without sequelae. The Francisella tularensis infection was eventually confirmed by microagglutination serologic assay. CONCLUSIONS If Parinaud oculoglandular syndrome is diagnosed and cat scratch fever as the most common etiology is not likely, other zoonoses, especially the oculoglandular form of tularemia, should be suspected. Serology is the most common laboratory method of diagnosing tularemia. Empiric fluoroquinolone (ciprofloxacin) or aminoglycoside (gentamicin or streptomycin) antibiotic therapy should be started immediately at the slightest suspicion of oculoglandular tularemia.
Topics: Humans; Male; Tularemia; Aged; Francisella tularensis; Conjunctivitis, Bacterial; Syndrome; Anti-Bacterial Agents; Ocular Motility Disorders; Lymphadenopathy
PubMed: 38941282
DOI: 10.12659/AJCR.943915 -
MBio Jun 2024Human adenoviruses (HAdVs) are small DNA viruses that generally cause mild disease. Certain strains, particularly those belonging to species B HAdVs, can cause severe...
Human adenoviruses (HAdVs) are small DNA viruses that generally cause mild disease. Certain strains, particularly those belonging to species B HAdVs, can cause severe pneumonia and have a relatively high mortality rate. Little is known about the molecular aspects of how these highly pathogenic species affect the infected cell and how they suppress innate immunity. The present study provides molecular insights into how species B adenoviruses suppress the interferon signaling pathway. Our study shows that these viruses, unlike HAdV-C2, are resistant to type I interferon. This resistance likely arises due to the highly efficient suppression of interferon-stimulated gene expression. Unlike in HAdV-C2, HAdV-B7 and B14 sequester STAT2 and RNA polymerase II from interferon-stimulated gene promoters in infected cells. This results in suppressed interferon- stimulated gene activation. In addition, we show that RuvBL1 and RuvBL2, cofactors important for RNA polymerase II recruitment to promoters and interferon-stimulated gene activation, are redirected to the cytoplasm forming high molecular weight complexes that, likely, are unable to associate with chromatin. Proteomic analysis also identified key differences in the way these viruses affect the host cell, providing insights into species B-associated high pathogenicity. Curiously, we observed that at the level of protein expression changes to the infected cell, HAdV-C2 and B7 were more similar than those of the same species, B7 and B14. Collectively, our study represents the first such study of innate immune suppression by the highly pathogenic HAdV-B7 and B14, laying an important foundation for future investigations.IMPORTANCEHuman adenoviruses form a large family of double-stranded DNA viruses known for a variety of usually mild diseases. Certain strains of human adenovirus cause severe pneumonia leading to much higher mortality and morbidity than most other strains. The reasons for this enhanced pathogenicity are unknown. Our study provides a molecular investigation of how these highly pathogenic strains might inactivate the interferon signaling pathway, highlighting the lack of sensitivity of these viruses to type I interferon in general while providing a global picture of how viral changes in cellular proteins drive worse disease outcomes.
PubMed: 38940561
DOI: 10.1128/mbio.01038-24 -
Frontiers in Bioscience (Landmark... Jun 2024This study aimed to elucidate the molecular mechanism through which C1q/tumor necrosis factor (TNF)-related protein 9 (CTRP9) acts in the formation and differentiation...
BACKGROUND
This study aimed to elucidate the molecular mechanism through which C1q/tumor necrosis factor (TNF)-related protein 9 (CTRP9) acts in the formation and differentiation of brown adipose tissue (BAT).
METHODS
Adenovirus particles encoding CTRP9 and green fluorescent protein were inoculated into the scapula of C57BL/6J mice and fed a high-fat diet for 8 weeks; the body weight, lipid droplet morphology, glucose tolerance, insulin tolerance, and protein expression levels were analyzed. In addition, CTRP9 adenovirus was transfected into brown preadipocytes, and differentiation was induced to identify the effect of CTRP9 overexpression on adipocyte differentiation.
RESULTS
CTRP9 overexpression significantly increased the weight gain of mice. Additionally, the CTRP9 overexpression group exhibited significantly increased adipose tissue weight and glucose clearance rates and decreased insulin sensitivity and serum triglyceride levels compared to the control group. Furthermore, CTRP9 overexpression significantly upregulated the adipose triglyceride lipase (ATGL) and perilipin 1 protein expression levels in BAT. The cell experiment results confirmed that CTRP9 overexpression significantly inhibited the adipogenesis of brown adipocytes as evidenced by the downregulation of uncoupling protein 1, beta-3 adrenergic receptor, ATGL, and hormone-sensitive lipase mRNA levels and the significant suppression of uncoupling protein 1, ATGL, and perilipin 1 protein levels in brown adipocytes.
CONCLUSIONS
The finding of this study demonstrated that CTRP9 promotes lipolysis by upregulating ATGL expression and inhibits the differentiation of brown preadipocytes .
Topics: Animals; Lipolysis; Diet, High-Fat; Adipose Tissue, Brown; Mice, Inbred C57BL; Male; Mice; Adiponectin; Insulin Resistance; Lipase; Cell Differentiation; Adipogenesis; Perilipin-1; Acyltransferases; Glycoproteins
PubMed: 38940054
DOI: 10.31083/j.fbl2906236 -
Cureus May 2024Gastroenteritis is a common cause of morbidity and mortality globally. Its cause encompasses a spectrum of agents, including viruses, bacteria, parasites, toxins, and...
BACKGROUND
Gastroenteritis is a common cause of morbidity and mortality globally. Its cause encompasses a spectrum of agents, including viruses, bacteria, parasites, toxins, and drugs. Viruses account for a considerable portion of gastroenteritis cases across all age groups, typically presenting with symptoms like nausea, vomiting, diarrhea, dehydration, anorexia, and weight loss. While sporadic cases occur, viral gastroenteritis is more frequently observed in outbreaks within closely knit communities such as daycare facilities, nursing homes, and cruise ships. Therefore, it becomes necessary to determine when healthcare providers should consider this condition in their differential diagnosis and to develop the most effective strategy to confirm the diagnosis.
METHODS
De-identified data of patients with gastroenteritis were collected over a five-year period utilizing the Patient Cohort Explorer, an electronic health record at the University of Mississippi Medical Center. Confirmatory laboratory tests employed the BioFire® FilmArray® multiplex polymerase chain reaction for gastrointestinal pathogens. Out of the 22 most common agents associated with gastroenteritis, only viral pathogens, specifically adenovirus, astrovirus, norovirus, rotavirus, and sapovirus, were included in the analysis. When available, histopathology was reviewed.
RESULTS
Among the various causes of gastroenteritis, both infectious and non-infectious, our findings revealed that 25.46% of the cases were linked to viral pathogens. This included a significantly higher percentage of pediatric patients (72.73%) when compared to adults (27.07%), with a p-value of 0.015. Norovirus genogroups I and II emerged as the most frequently detected viruses across all age groups, with a significant prevalence among adults. No discernible gender-based differences were observed. The histopathological findings included inflammation, ulceration, erosion, architectural distortion, and the pathognomonic viral inclusion bodies associated with adenovirus.
CONCLUSION
Our comprehensive analysis of viral gastroenteritis cases highlights the substantial burden of this condition, particularly among pediatric patients. Norovirus emerges as a prevalent culprit which emphasizes the importance of vigilant surveillance and timely diagnosis, especially in settings where outbreaks are common.
PubMed: 38939260
DOI: 10.7759/cureus.61197 -
Scientific Reports Jun 2024In contrast to transplant recipients, there is a paucity of data regarding frequency and clinical significance of viraemia in children receiving conventional... (Observational Study)
Observational Study
In contrast to transplant recipients, there is a paucity of data regarding frequency and clinical significance of viraemia in children receiving conventional chemotherapy. In a prospective observational study, we assessed the frequency of and clinical impact of viraemia with cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, human herpesvirus-6 (HHV6) and herpes-simplex virus 1/2 (HSV1/2) in paediatric cancer patients at diagnosis, at a routine examination during intensive chemotherapy, and during febrile neutropenia (FN). Seventy-nine patients (median age 6 years; 66 children with haematological malignancies) were included in the study. Overall, 362 blood samples were analysed, 72 from the time at diagnosis (11.1% with positive PCR result), 118 during a regular control after chemotherapy (11.0% positive), and 159 during FN (8.8% positive). The overall positivity rate was 9.6% (CMV 3.3%, HHV6 2.7%, HSV 2.2%, EBV 0.8% and adenovirus 0.3%). There were no significant differences between FN episodes with and without viraemia in terms of duration of fever or neutropenia/lymphopenia, severity of mucositis (> II), incidence of diarrhea and ICU admission. Our results indicate that viraemia in paediatric cancer patients generally does not have a major clinical impact, and may help in the decision regarding the indication of routine evaluation for viraemia in febrile neutropenic, but otherwise asymptomatic children.
Topics: Humans; Child; Viremia; Female; Male; Child, Preschool; Neoplasms; Adolescent; Prospective Studies; Infant; Febrile Neutropenia; Hematologic Neoplasms
PubMed: 38937530
DOI: 10.1038/s41598-024-65641-w -
Journal of Water and Health Jun 2024Ferrate (Fe(VI): HFeO /FeO), a potent oxidant, has been investigated as an alternative chemical disinfectant in water treatment due to its reduced production of...
Ferrate (Fe(VI): HFeO /FeO), a potent oxidant, has been investigated as an alternative chemical disinfectant in water treatment due to its reduced production of disinfection by-products. In this study, we assessed the disinfecting ability of potassium ferrate against a variety of microorganisms, including waterborne pathogens, under varying pH and water temperature conditions. We presented CT values, a metric of ferrate concentrations (C) and contact time (T), to quantify microbial inactivation rates. Among the tested microorganisms, human adenovirus was the least resistant to ferrate, followed by waterborne bacteria such as and , and finally, the protozoan parasite . We further investigated the impact of two pH values (7 and 8) and two temperatures (5 and 25 °C) on microbial inactivation rates, observing that inactivation rates increased with lower pH and higher temperature. In addition to showcasing ferrate's capacity to effectively inactivate a range of the tested microorganisms, we offer a ferrate CT table to facilitate the comparison of the effectiveness of various disinfection methods.
Topics: Hydrogen-Ion Concentration; Temperature; Disinfectants; Giardia lamblia; Adenoviruses, Human; Potassium Compounds; Water Microbiology; Disinfection; Water Purification; Iron Compounds; Humans; Escherichia coli
PubMed: 38935460
DOI: 10.2166/wh.2024.087 -
Clinical Cancer Research : An Official... Jun 2024An oncolytic adenovirus armed with tumor necrosis factor-α and interleukin-2 was tested in patients with advanced solid tumors. Antitumor effects were observed in both...
An oncolytic adenovirus armed with tumor necrosis factor-α and interleukin-2 was tested in patients with advanced solid tumors. Antitumor effects were observed in both treated and non-treated lesions, leading to long-term survival in some patients. This clinical trial shows the potential of oncolytic virotherapy for patients refractory to standard therapies.
PubMed: 38935348
DOI: 10.1158/1078-0432.CCR-24-1126 -
Investigational New Drugs Jun 2024HCC is the most common fatal malignancy. Although surgical resection is the primary treatment strategy, most patients are not eligible for resection due to tumor...
HCC is the most common fatal malignancy. Although surgical resection is the primary treatment strategy, most patients are not eligible for resection due to tumor heterogeneity, underlying liver disease, or comorbidities. Therefore, this study explores the possibility of multi-molecular targeted drug delivery in treating HCC. In this study, we constructed the recombinant adenovirus co-expressing apoptin and melittin (MEL) genes. The inhibitory effect of the recombinant adenovirus on hepatocellular carcinoma cells was detected through experiments on cell apoptosis, migration, invasion, and other factors. The tumor inhibitory effect in vivo was assessed using subcutaneous HCC mice. Results showed that recombinant adenovirus co-expressing anti-tumor genes TAT and apoptin, RGD and MEL can significantly inhibit the proliferation, migration, and invasion of HCC cells by inducing an increase in reactive oxygen species (ROS) levels, upregulation of apoptotic proteins such as Bax, cleaved caspase-3, and cleaved caspase-9, and downregulation of the anti-apoptotic protein Bcl-2. In subcutaneous HCC mice, recombinant adenovirus induced significant apoptosis in tumor, and inhibited tumor growth. In conclusion, recombinant adenovirus co-expressing apoptin and MEL can inhibit the growth and proliferation of tumor cells both in vivo and in vitro.
PubMed: 38935191
DOI: 10.1007/s10637-024-01453-z -
Vaccines Jun 2024Though children infected by SARS-CoV-2 generally experience milder symptoms compared to adults, severe cases can occur. Additionally, children can transmit the virus to...
Immunogenicity, Safety, and Immune Persistence of One Dose of SARS-CoV-2 Recombinant Adenovirus Type-5 Vectored Vaccine in Children and Adolescents Aged 6-17 Years: An Immunobridging Trial.
BACKGROUND
Though children infected by SARS-CoV-2 generally experience milder symptoms compared to adults, severe cases can occur. Additionally, children can transmit the virus to others. Therefore, the availability of safe and effective COVID-19 vaccines for children and adolescents is crucial.
METHOD
A single-center, randomized, double-blind clinical trial was conducted in Funing County, Yancheng City, Jiangsu Province, China. Healthy children and adolescents were divided into two subgroups (6-12 years old or 13-17 years old) and randomly assigned to one of three groups to receive one dose of Ad5-nCoV (3 × 10 vp/dose). Another group, aged 18-59, received one dose of Ad5-nCoV (5 × 10 vp/dose) as the control group. At 28, 90, 180, and 360 days post-vaccination, we measured the geometric mean titer (GMT)/concentration (GMC) of neutralizing and binding antibodies against the prototype SARS-CoV-2 strain, as well as serum antibody levels against the BA.4/5 variant. We also evaluated the incidence of adverse events within 28 days post-vaccination.
RESULTS
A total of 2413 individuals were screened from 3 June 2021 to 25 July 2021, of whom 2021 eligible participants were enrolled, including 1009 aged 6~17 years in the children and adolescent group and 1012 aged 18-59 years in the adults group. The GMT of anti-wild SARS-CoV-2 neutralizing antibodies was 18.6 (95% CI, 16.6-20.9) in children and adolescents and 13.2 (95% CI, 11.6-15.0) in adults on day 28. The incidence of solicited adverse reactions between the adult group (49.4% [124/251]) and the children and adolescent group (46.3% [156/337]) was not statistically significant. The neutralizing antibody levels decreased by a factor of 3.29 from day 28 to day 360 post-vaccination.
CONCLUSIONS
A single dose of Ad5-nCoV at 3 × 10 virus particles/dose is safe in children and adolescents, and it elicited significant immune response, which was not only non-inferior but also superior to that in adults aged 18-59 years.
PubMed: 38932412
DOI: 10.3390/vaccines12060683 -
Vaccines Jun 2024Inactivated and live attenuated vaccines are the mainstays of preventing viral poultry diseases. However, the development of recombinant DNA technology in recent years... (Review)
Review
Inactivated and live attenuated vaccines are the mainstays of preventing viral poultry diseases. However, the development of recombinant DNA technology in recent years has enabled the generation of recombinant virus vector vaccines, which have the advantages of preventing multiple diseases simultaneously and simplifying the vaccination schedule. More importantly, some can induce a protective immune response in the presence of maternal antibodies and offer long-term immune protection. These advantages compensate for the shortcomings of traditional vaccines. This review describes the construction and characterization of primarily poultry vaccine vectors, including fowl poxvirus (FPV), fowl adenovirus (FAdV), Newcastle disease virus (NDV), Marek's disease virus (MDV), and herpesvirus of turkey (HVT). In addition, the pathogens targeted and the immunoprotective effect of different poultry recombinant virus vector vaccines are also presented. Finally, this review discusses the challenges in developing vector vaccines and proposes strategies for improving immune efficacy.
PubMed: 38932359
DOI: 10.3390/vaccines12060630