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Poultry Science Oct 2023Pigeon paramyxovirus-1 (PPMV-1), a genetic variant of avian paramyxovirus-1 (APMV-1), has been identified in Columbiformes and is the primary cause of diseases in...
Pigeon paramyxovirus-1 (PPMV-1), a genetic variant of avian paramyxovirus-1 (APMV-1), has been identified in Columbiformes and is the primary cause of diseases in captive and free-ranging pigeons. However, it has also been reported that PPMV-1 can infect chickens naturally and experimentally, thus posing a potential threat to the poultry industry. This study investigated a lethal outbreak of paramyxovirus infection that occurred among 16 oriental turtle doves (Streptopelia orientalis) in a walk-in aviary at a zoo from March to April 2021. Necropsies were performed, and histopathological findings revealed mild to moderate lymphoplasmacytic infiltration in several organs, such as the pancreas, liver, kidneys, and lungs. Reverse transcription polymerase chain reaction (RT-PCR) using formalin-fixed paraffin-embedded tissue blocks, virus isolation from fresh tissue, and in situ hybridization against the fusion (F) protein confirmed the diagnosis for PPMV-1 infection. The isolated strain NTU/C239/21 was fully sequenced by next-generation sequencing, and the results of phylogenetic analyses revealed that the F protein of NTU/C239/21 shared 98.8% nucleotide sequence identity with Pigeon/Taiwan/AHRI121/2017, which was isolated from a feral pigeon in Taiwan. The present study is the first to identify PPMV-1 infection in Streptopelia orientalis and suggests that Streptopelia orientalis may also play an important role in spreading the infection, similar to pigeons in APMV-1 spreading.
Topics: Animals; Columbidae; Newcastle Disease; Phylogeny; Chickens; Newcastle disease virus; High-Throughput Nucleotide Sequencing; Genotype; In Situ Hybridization
PubMed: 37573845
DOI: 10.1016/j.psj.2023.102974 -
Signal Transduction and Targeted Therapy Apr 2024The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2...
The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.
Topics: Animals; Humans; Male; Mice; Angiotensin-Converting Enzyme 2; COVID-19; Fibroblast Growth Factor 7; Human Embryonic Stem Cells; Insulin Secretion; Islets of Langerhans; Organoids; SARS-CoV-2
PubMed: 38654010
DOI: 10.1038/s41392-024-01790-8 -
Open Forum Infectious Diseases Nov 2023Invasive fungal infections (IFIs) remain a rare yet dreaded complication following pancreas transplantation. Current guidelines recommend antifungal prophylaxis in...
BACKGROUND
Invasive fungal infections (IFIs) remain a rare yet dreaded complication following pancreas transplantation. Current guidelines recommend antifungal prophylaxis in patients with 1 or more risk factors. At our center, single-dose antifungal prophylaxis is administered in the operating room but none subsequently, regardless of risk factors. Here we evaluate the 1-year incidence, outcome, and risk factors associated with IFI following pancreas transplantation.
METHODS
A retrospective, single-center cohort study was conducted in patients who underwent pancreas transplantation between 1 January 2009 and 31 December 2019. Records were manually reviewed, and cases were adjudicated using consensus definitions. The 1-year cumulative incidence, mortality, and risk factors were analyzed by Kaplan-Meier method and differences between populations were assessed with Fisher test and Mann-Whitney test.
RESULTS
Three hundred sixty-nine recipients were included. Twelve IFIs were identified: candidiasis (8), aspergillosis (2), histoplasmosis (1), and cryptococcosis (1). Intra-abdominal infections were the most common presentation (5), followed by bloodstream infections (3), disseminated disease (2), pulmonary disease (1), and invasive fungal sinusitis (1). Median time to IFI was 64 days (interquartile range, 30-234 days). One-year cumulative incidence was 3.25% (95% confidence interval, 1.86%-5.65%). There were no significant differences between patients with or without IFI regarding type of transplant ( = .17), posttransplant dialysis ( = .3), rejection ( = .5), cytomegalovirus serostatus ( = .45), or reoperation ( = .19). For patients with IFI, the 1-year graft and patient survival rates were 58% versus 95% ( < .0001) and 75% versus 98.6% ( < .001), respectively.
CONCLUSIONS
Our study suggests that the use of a single-dose antifungal prophylaxis administered in the operating room but none subsequently does not result in an increased incidence of IFI following pancreas transplantation.
PubMed: 37942464
DOI: 10.1093/ofid/ofad478 -
Hepatology (Baltimore, Md.) Jul 2024Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP).
APPROACH AND RESULTS
We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC.
CONCLUSIONS
Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.
Topics: Humans; Genome-Wide Association Study; Liver Neoplasms; Genetic Predisposition to Disease; Carcinoma, Hepatocellular; Male; Female; Middle Aged; North America; Case-Control Studies; Polymorphism, Single Nucleotide; Aged; Genetic Loci; White People
PubMed: 38381705
DOI: 10.1097/HEP.0000000000000800 -
Cureus Jul 2023IgG4-related disease (IgG4-RD) is an immune-mediated disorder that involves multiple organs and is characterized by the infiltration of lymphoplasmacytic cells,...
IgG4-related disease (IgG4-RD) is an immune-mediated disorder that involves multiple organs and is characterized by the infiltration of lymphoplasmacytic cells, including IgG4-positive plasma cells, along with storiform fibrosis and obliterative phlebitis in the inflamed organs. The primary sites affected by this condition include the pancreas, bile ducts, salivary glands, aorta, lungs, kidneys, meninges, lacrimal glands, mediastinal lymph nodes, and retroperitoneum. The pathogenesis is linked to a type 2 T-helper-cell cytokine profile and the involvement of regulatory T cells. However, the exact mechanism is still unknown. Patients with IgG4-related disease are frequently misdiagnosed as having malignancies due to the resemblance of the lesions to infections or other immune-mediated diseases and certain tumors, such as pancreatic cancer and pseudo-renal pelvis tumor. Prompt identification of IgG4-related disease is essential as a delayed diagnosis until advanced stages can result in severe organ damage and potentially fatal outcomes, despite the disease being highly responsive to treatment. This report presents a highly unusual case of IgG4-related disease (IgG4-RD) with an atypical presentation in a 38-year-old female patient. The patient sought medical attention in the emergency department due to nasal septal erosions and an oral-antral fistula. Nasal cultures were conducted and indicated the presence of Klebsiella ozaena. Subsequent investigations, including a nasal biopsy, confirmed the diagnosis of IgG4-related autoimmune disease.
PubMed: 37637516
DOI: 10.7759/cureus.42475 -
Frontiers in Oncology 2024Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu, is routinely used to combat influenza...
PURPOSE
Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu, is routinely used to combat influenza infections. Although evidence has indicated the anti-cancer effects of OP and , little information is known about the effect of OP use on cancers in humans.
METHODS
A nationwide population-based cohort study involving 13,977,101 cases with 284,733 receiving OP was performed to examine the association between OP use and cancers using the National Health Insurance Research Database in Taiwan between 2009 and 2018.
RESULTS
The cohort study found that OP users showed a significantly lower incidence of lung cancer, colon cancer, liver, and intrahepatic bile duct cancer, oral cancer, pancreas cancer, esophagus cancer, stomach cancer, and prostate cancer. Additionally, OP users exhibited a lower risk of cancer-related mortality (adjusted HR=0.779; 95% confidence interval [CI] 0.743-0.817; p<0.001) and a reduced risk of developing liver cancer (adjusted HR=0.895; 95% CI 0.824-0.972; p=0.008), esophagus cancer (adjusted HR=0.646; 95% CI 0.522-0.799; p<0.001) and oral cancer (adjusted HR=0.587; 95% CI 0.346-0.995; p=0.048). Notably, OP users had a significant reduction in liver cancer occurrence over a 10-year period follow-up and a lower cancer stage at liver cancer diagnosis.
CONCLUSION
These findings first suggest the beneficial effects and therapeutic potential of OP use for certain cancers, especially liver cancer.
PubMed: 38469236
DOI: 10.3389/fonc.2024.1329986 -
Journal of Postgraduate Medicine 2023We describe a patient who presented with scrotal swelling followed by non-healing and discharging scrotal sinuses, following local trauma and was initially suspected to...
We describe a patient who presented with scrotal swelling followed by non-healing and discharging scrotal sinuses, following local trauma and was initially suspected to have an infected scrotal hematoma. An evaluation revealed it to be scrotal tuberculosis. He also complained of upper abdominal pain and on transabdominal ultrasonography was detected to have a mass in the head of the pancreas. Evaluation of the pancreatic mass revealed it to be pancreatic tuberculosis. Both lesions responded well to anti-tubercular therapy. This is an unusual case of two rare sites of extrapulmonary tuberculosis presenting simultaneously in the same individual. Care needs to be exercised while evaluating any non-healing ulcers or sinuses and mass lesions in countries endemic for tuberculosis as this disease can be a great masquerader.
Topics: Male; Humans; Tuberculosis; Pancreas; Genital Diseases, Male; Scrotum; Hematoma
PubMed: 36751759
DOI: 10.4103/jpgm.jpgm_558_22 -
Cureus Jan 2024A 54-year-old man was admitted for fever and dyspnea. He presented with severe COVID-19 pneumonia and elevated amylase and lipase levels. He received treatment for...
A 54-year-old man was admitted for fever and dyspnea. He presented with severe COVID-19 pneumonia and elevated amylase and lipase levels. He received treatment for COVID-19 and possible acute pancreatitis (AP). Although pneumonia and amylase levels improved, a high-grade fever persisted. On day 39, abdominal CT revealed heterogenous liquid and non-liquid components with a well-defined wall around the pancreas, and he was diagnosed with infected walled-off necrosis (WON) after AP. It was concluded to be associated with COVID-19 because there were no identifiable causes, such as alcohol consumption, gallstones, or other viral infections. The necrotic collection and fever improved after endoscopic transgastric drainage and necrosectomy. SARS-CoV-2 is becoming recognized as a new etiological infectious factor for AP, and COVID-19-associated AP shows higher severity and mortality. Clinicians should evaluate COVID-19 patients for concomitant AP, and if it is present, they should carefully monitor the development of local complications, including WON.
PubMed: 38327952
DOI: 10.7759/cureus.51889 -
Endoscopy International Open Sep 2023Recently studies have compared early (<4 weeks) vs. late or standard (>4 weeks) endoscopic treatment of pancreatic necrotic collections (PNC) and have reported... (Review)
Review
Recently studies have compared early (<4 weeks) vs. late or standard (>4 weeks) endoscopic treatment of pancreatic necrotic collections (PNC) and have reported favorable results for early treatment. In this meta-analysis, we compared the efficacy and safety of early vs. late endoscopic treatment of PNC. We reviewed several databases from inception to September 30, 2021 to identify studies that compared early with late endoscopic treatment of PNC. Our outcomes of interest were adverse events (AEs), resolution of PNC, performance of direct endoscopic necrosectomy, need for further interventions, and mean number of endoscopic necrosectomy sessions. We calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs) for categorical variables and mean differences (MDs) with 95% CIs for continuous variables. Data were analyzed by random effect model. Heterogeneity was assessed by I statistic. We included four studies with 427 patients. We found no significant difference in rates of AEs, RR (95% CI) 1.70 (range, 0.56-5.20), resolution of necrotic or fluid collections, RR (95% CI) 0.89 (range, 0.71-1.11), need for further interventions, RR (95% CI) 1.47 (range, 0.70-3.08), direct necrosectomy, RR (95% CI) 1.39 (range, 0.22-8.80), mortality, RR (95% CI) 2.37 (range, 0.26-21.72) and mean number of endoscopic necrosectomy sessions, MD (95% CI) 1.58 (range,-0.20-3.36) between groups. Early endoscopic treatment of PNC can be considered for indications such as infected necrosis or sterile necrosis with symptoms or complications; however, future large multicenter studies are required to further evaluate its safety.
PubMed: 37671081
DOI: 10.1055/a-2100-9076