Assessment of Torque Teno Virus (TTV) Frequency in Healthy Blood Donors in the Central Region of Iran, Yazd.

Background: Torque teno virus (TTV) is a globally prevalent virus in humans, yet comprehensive knowledge about its prevalence, predominant transmission routes, and pathogenesis remains limited. This study aimed to assess the frequency of TTV infection among healthy blood donors in Yazd, Iran. Materials and Methods: A total of 236 healthy blood donors, devoid of HIV/HBV/HCV infection markers, participated in the study from 2015 to 2016. Nested Polymerase Chain Reaction (PCR) utilizing a set of oligo primers for the 5΄- UTR region was employed to detect TTV DNA in serum samples. Results: The TTV genome was identified in 161 out of 236 (61.2%) healthy blood donors. The mean age for men and women was 43 and 57 years, respectively. Of the participants, 156 were male, and 107 were female. Donor age exhibited a significant association with virus presence (P=0.007); however, gender did not show a statistically significant association with the frequency of TTV infection in healthy blood donors (P=0.3). Conclusion: The study revealed a notably high frequency of the Torque teno virus in Yazd province, aligning with similar findings globally. Further investigations are warranted to elucidate the clinical implications of the virus in the healthy population.

Efficacy, immunogenicity, and safety of COVID-19 vaccines in individuals with liver cirrhosis: a rapid review and meta-analysis.

The emergence of coronavirus disease 2019 (COVID-19) vaccines has been a remarkable advancement. However, the efficacy, immunogenicity, and safety of these vaccines in individuals with liver cirrhosis require careful evaluation due to their compromised immune status and potential interactions with underlying liver disease. The present study aimed to evaluate the safety and efficacy of COVID-19 vaccines in liver cirrhosis patients. In the present study, we searched international databases, including Google Scholar, PubMed, Scopus, Embase, and Web of Science. The search strategy was carried out by using keywords and MeSH (Medical Subject Headings) terms. STATA ver. 15.0 (Stata Corp., USA) was used to analyze the data statistically. The analysis was performed using the random-effects model. We also used the chi-square test and I2 index to calculate heterogeneity among studies. For evaluating publication bias, Begg's funnel plots and Egger's tests were used. A total of 4,831 liver cirrhosis patients with COVID-19 were examined from 11 studies. The rate of hospitalization in the patients with liver cirrhosis was 17.6% (95% confidence interval [CI], 9%-44%). The rate of fever in the patients with liver cirrhosis was 4.5% (95% CI, 0.9%-8.1%). The rate of positive neutralizing antibodies in the patients with liver cirrhosis was 82.5% (95% CI, 69.8%-95.1%). Also, the rates of seroconversion after the second vaccination in patients with liver cirrhosis and the control group were 96.6% (95% CI, 92.0%-99.0%), and 99.7% (95% CI, 99.0%-100.0%), respectively. COVID-19 vaccines have demonstrated promising efficacy, immunogenicity, and safety profiles in individuals with liver cirrhosis, providing crucial protection against COVID-19-related complications.

Resveratrol and 1,25-dihydroxyvitamin D decrease Lingo-1 levels, and improve behavior in harmaline-induced Essential tremor, suggesting potential therapeutic benefits.

Essential tremor (ET) is a neurological disease that impairs motor and cognitive functioning. A variant of the Lingo-1 genetic locus is associated with a heightened ET risk, and increased expression of cerebellar Lingo-1. Lingo-1 has been associated with neurodegenerative processes; however, neuroprotection from ET-associated degeneration can be conferred by the protein Sirt1. Sirt1 activity can be promoted by Resveratrol (Res) and 1,25-dihydroxyvitamin D3 (VitD3), and thus these factors may exert neuroprotective properties through a Sirt1 mechanism. As Res and VitD3 are linked to Sirt1, enhancing Sirt1 could counteract the negative effects of increased Lingo-1. Therefore, we hypothesized that a combination of Res-VitD3 in a harmaline injection model of ET would modulate Sirt1 and Lingo-1 levels. As expected, harmaline exposure (10 mg/kg/every other day; i.p.) impaired motor coordination, enhanced tremors, rearing, and cognitive dysfunction. When Res (5 mg/kg/day; i.p.) and VitD3 (0.1 mg/kg/day; i.p.) were given to adult rats (n = 8 per group) an hour before harmaline, tremor severity, rearing, and memory impairment were reduced. Individual treatment with Res and VitD3 decreased Lingo-1 gene expression levels in qPCR assays. Co-treatment with Res and VitD3 increased and decreased Sirt1 and Lingo-1 gene expression levels, respectively, and in some cases, beneficial effects on behavior were noted, which were not seen when Res or VitD3 were individually applied. Taken together, our study found that Res and VitD3 improved locomotor and cognitive deficits, modulated Sirt1 and Lingo-1. Therefore, we would recommend co-treatment of VitD3 and Res to leverage complementary effects for the management of ET symptoms.

The Role of Epstein-Barr Virus (EBV) Infected Gastric Cancer in Increasing microRNA124 (miR-124) Promoter Methylation and Enhancer of Zeste Homolog 2 (EZH2) Gene Expression.

The tumor suppressor microRNAs, miR-21, miR-124, and miR-494, participate in the controlling several cellular processes. To assess target miRNAs promoter methylation levels, we investigated 304 pairs of gastric cancer (GC) tissues and non-tumor tissues. We used a commercial real-time polymerase chain reaction (RT-PCR) for Epstein-Barr virus (EBV) and Helicobacter pylori kit to detect EBV and H. pylori DNA in GC tissues. After finding hypermethylation in the promoter of the miR-124 gene, we evaluated its expression level using quantitative PCR (qPCR). Bioinformatics analysis confirmed miR-124 as a target of enhancer of Zeste homolog 2 (EZH2). Additionally, qPCR confirmed the association between EZH2 and miR-124. EBV and H. pylori DNA were detected in 9.5% and 15.1% of GC patients, respectively. Our findings also revealed significant differences in the miR-124 methylation levels among EBV-infected GC patients, H. pylori infected GC patients, GC patients without EBV and H. pylori infection, and non-tumor tissue. Bioinformatics and qPCR assays suggested an inverse relationship between the expression levels of EZH2 and miR-124 in EBV-infected GC patients. Our data revealed hypermethylation of the miR-124 promoter and significant reduction in its expression in EBV-infected GC tissues. It is possible that miR-124 may target EZH2 by binding to the 3'-UTR of the EZH2 gene, thus potentially contributing to the development of EBV-infected GC.

Novel Mutations in the Non-Structure Protein 2 of SARS-CoV-2.

Introduction: Mutation in the genome of SARS-CoV-2 may play a role in immune evasion, pathogenicity, and speed of its transmission. Our investigation aimed to evaluate the mutations that exist in the NSP2. Materials and Method: RNA was extracted from nasopharyngeal swabs from 100 COVID-19 patients. RT-PCR was performed on all samples using NSP2-specific primers. Following gel electrophoresis, the bands were cut, purified, and sequenced using the Sanger method. After sequencing, 90 sequences could be used for further analysis. Bioinformatics analysis was conducted to investigate the effect of mutations on protein structure, stability, prediction of homology models, and phylogeny tree. Results: The patients' mean age was 51.08. The results revealed that 8 of the 17 NSP2 mutations (R207C, T224I, G262V, T265I, K337D, N348S, G392D, and I431M) were missense. One deletion was also found in NSP2. Among NSP2 missense mutations studied, K337D and G392D increased structural stability while the others decreased it. The homology-designed models demonstrated that the homologies were comparable to the sequences of the Wuhan-HU-1 virus. Conclusion: Our study suggested that the mutations K337D and G392D modulate the stability of NSP2, and tracking viral evolution should be implemented and vaccine development updated.

Assessment of the Effect of Sub-Cutaneous Adalimumab on Prognosis of COVID-19 Patients: a Non-Randomized Pilot Clinical Trial Study in Iran.

BACKGROUND: Adalimumab is an anti-inflammatory medicine used to treat a variety of disorders, although its effectiveness in improving the clinical status of COVID-19 patients is debatable. The goal was to evaluate the efficacy of adalimumab as an alternate treatment in COVID-19 patients. METHODS: This non-randomized pilot clinical trial study included 18 patients with severe COVID-19 status hospitalized at the Afzalipour Hospital in Kerman from February 2022 to March 2022. Patients were divided into two groups: nine patients in the control group received dexamethasone, remdesivir, and heparin in addition to supportive therapies. The case group also included nine patients who received adalimumab injection (CinnoRA®, CinnaGen, Iran) in addition to the treatment administered to the control group. RESULTS: Although the effect of adalimumab injection on clinical factors, including mechanical ventilation required, the number of days oxygen needed, the length of stay in the intensive care unit (ICU), and saturation of peripheral oxygen (SpO2) level and respiratory rate (RR), were not significantly different between groups, the intra-group SpO2 level before and after receiving oxygen was significantly different in the case group (p ≤ 0.001 and p = 0.002). In addition, laboratory tests for lactate dehydrogenase (LDH) and C-reactive protein (CRP) revealed no statistically significant differences between the two groups. Nonetheless, a positive intra-group effect of the medication was detected on these two parameters. No short-term side effects of drug injection were observed. CONCLUSIONS: This study demonstrated the efficacy of adalimumab as an alternate medication for improving SpO2, LDH, and CRP levels in COVID-19 patients.

Evaluation of hematological parameters alterations in different waves of COVID-19 pandemic: A cross-sectional study.

BACKGROUND: The occurrence of variations in routine hematological parameters is closely associated with disease progression, the development of severe illness, and the mortality rate among COVID-19 patients. This study aimed to investigate hematological parameters in COVID-19 hospitalized patients from the 1st to the 5th waves of the current pandemic. METHODS: This cross-sectional study included a total of 1501 hospitalized patients with laboratory-confirmed COVID-19 based on WHO criteria, who were admitted to Shahid Sadoughi Hospital (SSH) in Yazd, Iran, from February 2020 to September 2021. Throughout, we encountered five COVID-19 surge waves. In each wave, we randomly selected approximately 300 patients and categorized them based on infection severity during their hospitalization, including partial recovery, full recovery, and death. Finally, hematological parameters were compared based on age, gender, pandemic waves, and outcomes using the Mann-Whitney U and Kruskal-Wallis tests. RESULTS: The mean age of patients (n = 1501) was 61.1±21.88, with 816 (54.3%) of them being men. The highest mortality in this study was related to the third wave of COVID-19 with 21.3%. There was a significant difference in all of the hematological parameters, except PDW, PLT, and RDW-CV, among pandemic waves of COVID-19 in our population. The highest rise in the levels of MCV and RDW-CV occurred in the 1st wave, in the 2nd wave for lymphocyte count, MCHC, PLT count, and RDW-SD, in the 3rd wave for WBC, RBC, neutrophil count, MCH, and PDW, and in the 4th wave for Hb, Hct, and ESR (p < 0.01). The median level of Hct, Hb, RBC, and ESR parameters were significantly higher, while the mean level of lymphocyte and were lower in men than in women (p < 0.001). Also, the mean neutrophil in deceased patients significantly was higher than in those with full recovered or partial recovery (p < 0.001). CONCLUSION: The findings of our study unveiled notable variations in hematological parameters across different pandemic waves, gender, and clinical outcomes. These findings indicate that the behavior of different strains of the COVID-19 may differ across various stages of the pandemic.

Higher Risk of Chronic Hepatitis E Virus Infection in Patients with Human Immunodeficiency Virus-1: An Iranian Cross-sectional Study.

Background & Objective: Occurrence of Hepatitis E Virus (HEV) infection may be common in Human Immunodeficiency Virus (HIV-1) patients and may lead to chronic infection as well as cirrhosis. We intended to determine the incidence of HEV infection among HIV-1 patients compared to individuals without HIV-1 infection. Methods: In our cross-sectional study, 87 HIV-1-positive patients were compared to 93 healthy individuals in Kerman, Iran. Plasma and peripheral blood mononuclear cells (PBMCs) were obtained from all the participants. Plasma samples were evaluated for HEV IgM and IgG using the ELISA kit. Then, reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) was used in RNA extractions from PBMCs to check for the presence of HEV RNA. Results: Among the subjects examined in our study, 61 (70.1%) and 71 (77.4%) out of patients with HIV-1 infection and healthy individuals were male, respectively. The average ages of patients with HIV-1 and the control group were 40.2 years and 39.9 years, respectively. No discernible differences were found between the two groups based on IgM and IgG seropositivity against the HEV. However, HEV-RNA was found in 8% of patients with HIV-1 and 1.1% of HIV-1-negative individuals (P=0.03). There was also an association between the HEV genome and anti-HEV and anti-HCV antibodies in HIV-1-positive patients (P=0.02 and P=0.014, respectively). Conclusion: HEV infection may be more common in HIV-1 patients and may develop a chronic infection in immunocompromised individuals. Molecular-based HEV diagnostic tests, including RT-PCR assays, should be performed in HIV-1 patients with unknown impaired liver function tests.

Global Trend on Machine Learning in Helicobacter within One Decade: A Scientometric Study.

Purpose: This study aims to create a science map, provide structural analysis, investigate evolution, and identify new trends in Helicobacter pylori (H. pylori) research articles. Methods: All Helicobacter publications were gathered from the Web of Science (WoS) database from August 2010 to 2021. The data were required for bibliometric analysis. The bibliometric analysis was performed with Bibliometrix R Tool. Bibliometric data were analyzed using the Bibliometrix Biblioshiny R-package software. Results: A total of 17,413 articles were reviewed and analyzed, with descriptive characteristics of the H. pylori literature included. In journals, 21,102 keywords plus and 20,490 author keywords were reported. These articles were also written by 56,106 different authors, with 262 being single-author articles. Most authors' abstracts, titles, and keywords included "Helicobacter-pylori." Since 2010, the total number of H. pylori-related publications has been decreasing. Gut, PLOS ONE, and Gastroenterology are the most influential H. pylori journals, according to source impact. China, the United States, and Japan are the countries with most affiliations and subjects. In addition, Seoul National University has published the most articles about H. pylori. According to the cloud word plot, the authors' most frequently used keywords are gastric cancer (GC), H. pylori, gastritis, eradication, and inflammation. "Helicobacter pylori" and "infection" have the steepest slopes in terms of the upward trend of words used in articles from 2010 to 2021. Subjects such as GC, intestinal metaplasia, epidemiology, peptic ulcer, eradication, and clarithromycin are included in the diagram's motor theme section, according to strategic diagrams. According to the thematic evolution map, topics such as Helicobacter pylori infection, B-cell lymphoma, CagA, Helicobacter pylori, and infection were largely discussed between 2010 and 2015. From 2016 to 2021, the top topics covered included Helicobacter pylori, H. pylori infection, and infection.

A comprehensive review of highly pathogenic avian influenza (HPAI) H5N1: An imminent threat at doorstep.

Avian influenza viruses (AIVs) are globally challenging due to widespread circulation and high mortality rates. Highly pathogenic avian influenza (HPAI) strains like H5N1 have caused significant outbreaks in birds. Since 2003 to 14 July 2023, the World Health Organization (WHO) has documented 878 cases of HPAI H5N1 infection in humans and 458 (52.16%) fatalities in 23 countries. Recent outbreaks in wild birds, domestic birds, sea lions, minks, and etc., and the occurrence of genetic variations among HPAI H5N1 strains raise concerns about potential transmission and public health risks. This paper aims to provide a comprehensive overview of the current understanding and new insights into HPAI H5N1. It begins with an introduction to the significance of studying this virus and highlighting the need for updated knowledge. The origin and evaluation of HPAI H5N1 are examined, shedding light on its emergence, and spread across different geographic regions. The genome organization and structural biology of the H5N1 virus are explored, providing insights into its molecular composition and key structural features. This manuscript also delves into the phylogeny, evolution, mutational trends, reservoirs, and transmission routes of HPAI H5N1. The immune response against HPAI H5N1 and its implications for vaccine development are analyzed, along with an exploration of the pathogenesis and clinical manifestations of HPAI H5N1 in human cases. Furthermore, diagnostic tools and preventive and therapeutic strategies are discussed, highlighting the current approaches and potential future directions for better management of the potential pandemic.

Beyond skin deep: shedding light on the neuropsychiatric consequences of Monkeypox (Mpox).

This review is attempted in view of World Health Organization (WHO) warning on Monkeypox virus (Mpox) to summarize the available data regarding the potential effect on central nervous system (CNS), its complications, and diagnostic methods. We combed various international databases (including Scopus, PubMed, Web of Science, and Google Scholar) for articles mentioning Mpox infection, orthopox infection, and the central nervous system that were published between the years 2000 and 2022. Further evidence was evaluated from relevant studies published in the literature. There is emerging evidence of central nervous system neurological involvement. In addition to encephalopathy, which is one of the most serious neurological complications of Mpox, the most common complications of Mpox infection are headache, weakness, myalgia, anorexia, and altered consciousness. Anxiety and depression have also been identified as the most common psychiatric symptoms in these patients.

Kawasaki disease in children: a retrospective cross-sectional study.

Introduction: Kawasaki disease (KD) is a systemic vasculitis, seen mostly in children. Epidemiology of KD is dependent on geographical location and seasonality. Although many years have passed since the first report of KD, multiple related factors are still unknown. Material and methods: We investigated the clinical, paraclinical, and therapeutic aspects of KD in Kerman, Iran by performing a retrospective, descriptive, cross-sectional study on all children hospitalized due to KD between 2007 and 2020. Results: A total of 340 patients with mean ±SD age of 29.83 ±22.55 months participated in the study. Most of our patients were two to five years old. The male : female ratio was ~ 1.4 : 1. A few of our patients had a family history of KD or vasculitis (0.3%, 1.7%). Typical KD was more common by a large margin (316 patients with typical KD). More than half of our patients had a duration of hospitalization of under ten days. All of our patients were febrile. Hand/foot and lip/mouth changes were the second and third most common clinical findings in more than 60% of our patients. Other manifestations were conjunctivitis in 40%, skin rashes in 34.8%, gastrointestinal manifestations in 33.9%, and lymphadenopathy in 25.3%. Echocardiography revealed abnormalities in 78.6% of the participants; coronary artery aneurysm (CAA) was the most frequent (22.5%) and follow-up echocardiography revealed that all of them regressed within 6 months after treatment. The two laboratory tests with the highest ratio of abnormality were erythrocyte sedimentation rate (95%) and hemoglobin (83.3%). C-reactive protein and liver function tests were also abnormal in most patients. All of our patients received intravenous immunoglobulin and acetylsalicylic acid. Conclusions: Kawasaki disease must be considered in every febrile child, especially those with risk factors, because timely diagnosis and treatment are essential to prevent complications. Health policies should focus on appropriate diagnosis and treatment to prevent the occurrence of sequelae.

Spontaneous pneumothorax with isolated pulmonary Langerhans cell histiocytosis in an adult case: A common manifestation of rare disease.

Key Clinical Message: Pulmonary Langerhans cell histiocytosis should be evaluated even in adults with no previous medical history and no history of cigarette smoking who have spontaneous pneumothorax and evidence of multiple lung cystic lesions, and other organs should also be checked for multi organ Langerhans cell histiocytosis involvement. Abstract: A 30-year-old man presented with sudden chest pain and evidence of multiple cystic lesions in both upper and lower lobes of lungs, as well as left-sided pneumothorax in high resolution computed tomography. In lung samples, hematoxylin and eosin- stained sections and IHC for CD1a, S100, and BRAF V600 were positive. The patient was diagnosed with isolated pulmonary Langerhans cell histiocytosis and was treated accordingly.

Mediterranean spotted fever as a non-endemic disease in the southeast of Iran: Diagnosis and treatment based on specific skin lesion.

Key Clinical Message: Rickettsia spp. should be investigated if Tache Noire, as a dark plaque covering a superficial ulcer surrounded by scale, edema, and erythema, are observed, even in non-endemic areas of Rickettsia spp. Abstract: A 31-year-old man with fever, dyspnea, abdominal pain, and jaundice has been admitted to the hospital in the southeast of Iran. Due to the presence of a pathognomonic skin lesion (Tache noire), the patient was diagnosed with Mediterranean spotted fever (MSF) and was treated with doxycycline, without waiting for PCR and IFA findings.

Ileocecal intussusception as a first presentation of Burkitt's lymphoma with multi-organ involvement.

Key Clinical Message: In children, intussusception may have a pathologic cause, such as Burkitt's lymphoma. As a result, we should be cautious of Burkitt's lymphoma in children with intussusception. Finally, the importance of histological assessment of resected tissues in pediatric operations, particularly those with intussusception, should be emphasized. Abstract: A 2-year-old boy was diagnosed with ileocecal intussusception and underwent surgical treatment and appendectomy. Appendix histopathology revealed lymphoid cells with hyperchromatic nuclei, high mitotic activity, and starry sky appearance. The patient was diagnosed with Burkitt's lymphoma, which involves many organs, such as the appendix, liver, kidney, and bone marrow.

HAV-induced acalculous cholecystitis: A case report and literature review.

Hepatitis A virus (HAV) has some life-threatening extrahepatic complications, such as acute acalculous cholecystitis (AAC). We present HAV-induced AAC in a young female, based on clinical, laboratory, and imaging findings, and conduct a literature review. The patient became irritable, which progressed to lethargy, as well as a significant decline in liver function, indicating acute liver failure (ALF). She was immediately managed in the intensive care unit with close airway and hemodynamic monitoring after being diagnosed with ALF (ICU). The patient's condition was improving, despite only close monitoring and supportive treatment with ursodeoxycholic acid (UDCA) and N-acetyl cysteine (NAC).

The complexity of human papilloma virus in cancers: a narrative review.

Among human tumorigenic viruses, the role of Human papillomavirus (HPV) has been proven as one of the most important oncoviruses that are associated with a large number of cancers. Most cancers of the genital area such cervical and anal cancer as are caused by HPV, and in many other cancers, such as colorectal, gastric, liver, esophageal, urinary bladder, and head and neck cancers, it is considered as one of the important risk factors. Our search was conducted for published researches between 2000 and 2022 by using several international databases including Scopus, PubMed, and Web of Science as well as Google scholar. We also evaluated additional evidence from relevant published articles. It has been demonstrated that HPV can promote tumorigenesis via focusing on genes, proteins, and signaling pathways, by using E6 and E7 oncoproteins and inhibiting two crucial tumor suppressors, P53 and Rb. The following study was performed to investigate different malignant cancers under the influence of HPV infection and changes in molecular factors caused by HPV infection.

Monkeypox virus diagnosis and laboratory testing.

The multi-country outbreak of monkeypox virus (MPXV) infection, while the coronavirus disease 2019 pandemic is still an ongoing issue, has caused a new challenge. The re-emergence of MPXV and the rising incidence in non-endemic countries is turning into an upcoming threat to global health. Hence, rapid identification of the virus with appropriate methodology with the lowest false results plays a critical role in estimating the global extent of the crisis and providing preventive measures. This review summarised the main applicable strategies for primary detection and confirmation of MPXV and highlighted available data in biosafety, requirements, standard operating procedures, specimen collection, transportation and storage of clinical samples, and waste disposal of the viral agent. Also, various assays including molecular techniques, immunoassays, histopathological methods, electron microscopy, genomic sequencing, and cell culture have been illustrated. Moreover, we reflected on current knowledge of the advantages and disadvantages of each approach.

Small extracellular vesicles as key players in cancer development caused by human oncogenic viruses.

BACKGROUND: Exosomes are the smallest group of extracellular vesicles in size from 30 to 150 nm, surrounded by a lipid bilayer membrane, and originate from multivesicular bodies secreted by different types of cells, such as virus-infected cells. The critical role of exosomes is information transfer among cells, representing a unique way for intercellular communication via a load of many kinds of molecules, including various signaling proteins and nucleic acids. In this review, we aimed to comprehensively investigate the role of exosomes in promoting human oncogenic viruses-associated cancers. METHODS: Our search was conducted for published researches between 2000 and 2022 by using several international databases includeing Scopus, PubMed, and Web of Science as well as Google scholar. We also reviewed additional evidence from relevant published articles. RESULTS: It has been shown that exosomes can create the conditions for viral spread in viral infections. Exosome secretion in a human tumor virus can switch on the cell signaling pathways by transferring exosome-encapsulated molecules, including viral oncoproteins, signal transduction molecules, and virus-encoded miRNAs, into various cells. CONCLUSION: Given the role of exosomes in viruses-associated cancers, they can also be considered as molecular targets in diagnosis and treatment.