Evaluation of a virus derived from MDCK cells infected persistently with influenza A virus as a potential live-attenuated vaccine candidate in the mouse model

A temperature-sensitive mutant virus unable to replicate at 38 degrees C was recovered from passage 189 (IVpi-189) of Madin-Darby canine kidney cells infected persistently with influenza A. Immunofluorescent staining of the IVpi-189 virus-infected cells revealed disrupted transport of the matrix (M) 1 protein into the nucleus at non-permissive temperatures, resulting in retention of the nucleoprotein (NP) in the nucleus. Upon comparison with the parental influenza A E61-24-P15 strain used to establish persistent infection, amino acid exchanges were found in the M1 protein of IVpi-189 virus; arginine to glutamine at position 72 and threonine to alanine at position 139. When mice were inoculated intranasally with IVpi-189 virus, virus growth in the lungs was restrained and terminated rapidly. Prior intranasal inoculation with only a small dose of IVpi-189 virus induced humoral and cellular immune responses and protected mice against subsequent virulent virus challenge. These results indicate that IVpi-189 virus, an avirulent temperature-sensitive mutant, is a promising candidate for use as a live-attenuated vaccine.     

Expression of RAB27B is up-regulated in senescent human cells

Immortal SVts8 cells that express thermolabile SV40 T antigen exhibit a senescence-like phenomenon upon inactivation of the T antigen. By using a cDNA subtractive hybridization technique, RAB27B, a member of the RAB GTPase family, was found to be up-regulated in senescent SVts8 cells. The up-regulation of RAB27B depends on the p53 gene. Enhanced expression was also observed in replicative senescence in normal human fibroblasts.     

Microbiome analysis revealing microbial interactions and secondary bacterial infections in COVID-19 patients comorbidly affected by Type 2 diabetes

The mortality of coronavirus disease 2019 (COVID-19) disease is very high among the elderly or individuals having comorbidities such as obesity, cardiovascular diseases, lung infections, hypertension, and/or diabetes. Our study characterizes the metagenomic features in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients with or without type 2 diabetes, to identify the microbial interactions associated with its fatal consequences.This study compared the baseline nasopharyngeal microbiome of SARS-CoV-2-infected diabetic and nondiabetic patients with controls adjusted for age and gender. The metagenomics based on next-generation sequencing was performed using Ion GeneStudio S5 Series and the data were analyzed by the Vegan-package in R. All three groups possessed significant bacterial diversity and dissimilarity indexes (p < 0.05). Spearman's correlation coefficient network analysis illustrated 183 significant positive correlations and 13 negative correlations of pathogenic bacteria (r = 0.6–1.0, p < 0.05), and 109 positive correlations between normal flora and probiotic bacteria (r > 0.6, p < 0.05). The SARS-CoV-2 diabetic group exhibited a significant increase in pathogens and secondary infection-causing bacteria (p < 0.05) with a simultaneous decrease of normal flora (p < 0.05). The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19-infected diabetic patients, although a few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal flora and probiotics through dietary supplementation and excessive inflammation reduction by preventing secondary infections might lead to a better outcome for those comorbid patients.     

SARS-CoV-2 and dengue virus co-infection: Epidemiology,pathogenesis, diagnosis,treatment, and management

SARS-CoV-2 and dengue virus co-infection cases have been on the rise in dengue-endemic regions as coronavirus disease 2019 (COVID-19) spreads over the world, posing a threat of a co-epidemic. The risk of comorbidity in co-infection cases is greater than that of a single viral infection, which is a cause of concern. Although the pathophysiologies of the two infections are different, the viruses have comparable effects within the body, resulting in identical clinical symptoms in the case of co-infection, which adds to the complexity. Overlapping symptoms and laboratory features make proper differentiation of the infections important. However, specific biomarkers provide precise results that can be utilised to diagnose and treat a co-infection, whether it is simply COVID-19, dengue, or a co-infection. Though their treatment is distinguished, it becomes more complicated in circumstances of co-infection. As a result, regardless of whatever infection the first symptom points to, confirmation diagnosis of both COVID-19 and dengue should be mandatory, particularly in dengue-endemic regions, to prevent health deterioration in individuals treated for a single infection. There is still a scarcity of concise literature on the epidemiology, pathophysiology, diagnosis, therapy, and management of SARS-CoV-2 and dengue virus co-infection. The epidemiology of SARS-CoV-2 and dengue virus co-infection, the mechanism of pathogenesis, and the potential impact on patients are summarised in this review. The possible diagnosis with biomarkers, treatment, and management of the SARS-CoV-2 and dengue viruses are also discussed. This review will shed light on the appropriate diagnosis, treatment, and management of the patients suffering from SARS-CoV-2 and dengue virus co-infection.     

Cryptosporidiosis: a cause of diarrhea in Bangladesh

Fecal samples from diarrheal patients and non-diarrheal controls were examined for Cryptosporidium oocysts in a year-long prospective study at a diarrhea treatment center in Dhaka, Bangladesh. Cryptosporidium oocysts were detected in 42 (3%) of 1,382 diarrheal patients but in none of 235 non-diarrheal controls. In 32 (76%) of 42 patients, no other enteropathogens were detected. Children less than 5 years of age were more commonly infected than older children (4.8% vs. 1.6%, P greater than 0.05) and adults (4.8% vs. 0.2%, P less than 0.01). A higher number of cases were detected during hot and humid months (April--July). Nineteen children less than 5 years of age (index cases) and their 71 family members were followed for 3 weeks after the release of the index cases from the hospital. Diarrhea continued for greater than 14 days (persistent diarrhea) in 8 (32%) index children. Cryptosporidium oocysts were detected in 1 (12.5%) of 8 family members who developed diarrhea during the follow-up period. Index cases excreted oocysts for 3-28 days (12.37 +/- 8.35 days). Almost all the patients recovered with oral rehydration. Cryptosporidium ssp. cause self-limited diarrhea episodes in children less than 5 years of age in Bangladesh, with a low frequency of intrafamilial transmission.     

Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases

Adenoid cystic/basal cell carcinoma (ACBCC) of the prostate has been considered to have indolent biologic potential. However, outcome data are scant, with only one documented metastasis and death. We describe clinicopathologic features of ACBCC in 19 patients and document outcome in 15. Patients ranged in age from 43 to 83 years. All but one presented with urinary obstruction. ACBCC was diagnosed by transurethral resection in 15 cases, by needle biopsy in 3 cases, and unexpected in 1 case. Four patients had concurrent acinar adenocarcinoma. Histologically, cribriform or adenoid cystic patterns predominated in 12 cases and basal cell carcinoma pattern in 7. Five cases had prominent perineural invasion. ACBCC was immunoreactive for p63 and cytokeratins 7 and 34 beta E12 but not cytokeratin 20. After diagnosis, 5 patients underwent radical prostatectomy, 2 underwent pelvic exenteration, and the rest had no treatment. ACBCC showed extraprostatic extension in 5 cases and involved the bladder margin in 3. Metastases developed in 4 (21%) patients: liver (2), lung (2), bowel (1), and corpus cavernosum (1). In 15 cases with follow-up (0.3-11.8 years), two patients died of cancer (at 1.5 and 3 years after diagnosis), 3 remain alive with cancer, and 10 have no evidence of cancer. Thus, ACBCC of the prostate is a potentially aggressive neoplasm requiring ablative therapy.     

Emergence and Distribution of Foot‐and‐Mouth Disease Virus Serotype A and O in Bangladesh

Foot‐and‐mouth disease (FMD) is endemic in Bangladesh and is predominantly due to FMDV serotype O. In 2012, FMD outbreaks were identified in five different districts of Bangladesh. Of 56 symptomatic cattle epithelial tissue samples, diagnostic PCR assay based on 5′‐URT detected 38 FMDV infections. Viral genotyping targeting VP1‐encoding region confirmed emergence of two distinct serotypes, A and O with an abundance of serotype A in Chittagong and Gazipur districts and serotype O in Pabna and Faridpur. Only single lineage of both A and O was retrieved from samples of five different regions. Sequencing and phylogenetic analysis of VP1 sequences revealed that serotype O sequences were closely related to the Ind 2001 sublineage of Middle East–South Asia (ME‐SA) topotype that was previously circulating in Bangladesh, and serotype A sequences belonging to the genotype VII that was dominant in India during the last decade. The results suggest that extensive cross‐border animal movement from neighbouring countries is the most likely source of FMDV serotypes in Bangladesh.     

Impact of donor age on survival and fibrosis progression in patients with hepatitis C undergoing liver transplantation using HCV+ allografts.

Studies have suggested that the use of hepatitis C virus (HCV)-positive (HCV+) donor allografts has no impact on survival. However, no studies have examined the effect that HCV+ donor histology has upon recipient and graft survival. We evaluated the clinical outcome and impact of histological features in HCV patients transplanted using HCV+ livers. We reviewed all patients transplanted for HCV at our institution from 1988 to 2004; 39 received HCV+ allografts and 580 received HCV-negative (HCV-) allografts. Survival curves compared graft and patient survival. Each HCV+ allograft was stringently matched to a control of HCV- graft recipients. No significant difference in survival was noted between recipients of HCV+ livers and controls. Patients receiving HCV+ allografts from older donors (age > or =50 yr) had higher rates of graft failure (hazard ratio, 2.74) and death rates (hazard ratio, 2.63) compared to HCV- allograft recipients receiving similarly-aged older donor livers. Matched case-control analysis revealed that recipients of HCV+ allografts had more severe fibrosis post-liver transplantation than recipients of HCV- livers (P = 0.008). More advanced fibrosis was observed in HCV+ grafts from older donors compared to HCV+ grafts from younger donors (P = 0.012). In conclusion, recipients of HCV+ grafts from older donors have higher rates of death and graft failure, and develop more extensive fibrosis than HCV- graft recipients from older donors. Recipients of HCV+ grafts, regardless of donor age, develop more advanced liver fibrosis than recipients of HCV- grafts.     

Explaining endograft shortening during endovascular repair of abdominal aortic aneurysms in severe aortoiliac tortuosity

Objective

During endovascular aneurysm repair (EVAR), severely tortuous aortoiliac anatomy can alter the deployment and conformability of the endograft. The accuracy of treatment length measurements is commonly recognized to be affected by severe tortuosity. However, the exact mechanism of the postintervention length discrepancy is poorly understood. The objective of this study was to determine the mechanism of how severe aortoiliac tortuosity influences the endograft and native aorta during EVAR and its impact on the distal sealing zone.

Identification and Characterization of microRNAs Associated With Human β‐Cell Loss in a Mouse Model

Currently there is no effective approach for monitoring early β‐cell loss during islet graft rejection following human islet transplantation (HIT). Due to ethical and technical constraints, it is difficult to directly study biomarkers of islet destruction in humans. Here, we established a humanized mouse model with induced human β‐cell death using adoptive lymphocyte transfer (ALT). Human islet grafts of ALT‐treated mice had perigraft lymphocyte infiltration, fewer insulin⁺ β cells, and increased β‐cell apoptosis. Islet‐specific miR‐375 was used to validate our model, and expression of miR‐375 was significantly decreased in the grafts and increased in the circulation of ALT‐treated mice before hyperglycemia. A NanoString expression assay was further used to profile 800 human miRNAs in the human islet grafts, and the results were validated using quantitative real‐time polymerase chain reaction. We found that miR‐4454 and miR‐199a‐5p were decreased in the human islet grafts following ALT and increased in the circulation prior to hyperglycemia. These data demonstrate that our in vivo model of induced human β‐cell destruction is a robust method for identifying and characterizing circulating biomarkers, and suggest that miR‐4454 and miR‐199a‐5p can serve as novel biomarkers associated with early human β‐cell loss following HIT.