Phylogenetic and Geospatial Evidence of Canine Parvovirus Transmission between Wild Dogs and Domestic Dogs at the Urban Fringe in Australia

Canine parvovirus (CPV) is an important cause of disease in domestic dogs. Sporadic cases and outbreaks occur across Australia and worldwide and are associated with high morbidity and mortality. Whether transmission of CPV occurs between owned dogs and populations of wild dogs, including Canis familiaris, Canis lupus dingo and hybrids, is not known. To investigate the role of wild dogs in CPV epidemiology in Australia, PCR was used to detect CPV DNA in tissue from wild dogs culled in the peri-urban regions of two Australian states, between August 2012 and May 2015. CPV DNA was detected in 4.7% (8/170). There was a strong geospatial association between wild-dog CPV infections and domestic-dog CPV cases reported to a national disease surveillance system between 2009 and 2015. Postcodes in which wild dogs tested positive for CPV were 8.63 times more likely to also have domestic-dog cases reported than postcodes in which wild dogs tested negative (p = 0.0332). Phylogenetic analysis of CPV VP2 sequences from wild dogs showed they were all CPV-2a variants characterized by a novel amino acid mutation (21-Ala) recently identified in CPV isolates from owned dogs in Australia with parvoviral enteritis. Wild-dog CPV VP2 sequences were compared to those from owned domestic dogs in Australia. For one domestic-dog case located approximately 10 km from a wild-dog capture location, and reported 3.5 years after the nearest wild dog was sampled, the virus was demonstrated to have a closely related common ancestor. This study provides phylogenetic and geospatial evidence of CPV transmission between wild and domestic dogs in Australia

Photoelectrochemical Valorization of Biomass Derivatives with Hematite Photoanodes Modified by Cocatalysts

The solar-driven oxidation of biomass to valuable chemicals is rising as a promising anodic reaction in photoelectrochemical cells, replacing the sluggish oxygen evolution reaction and improving the added value of the energy conversion process. Herein, the photooxidation of 5-hydroxymethylfurfural into furan dicarboxylic acid (FDCA) is performed in basic aqueous environment (borate buffer, pH 9.2), with the addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as redox mediator. Because of its good stability, cost-effectiveness, and nontoxicity, titanium-modified hematite (Ti:Fe2O3) photoanodes are investigated to this aim, and their performance is tuned by engineering the semiconductor surface with a thin layer of Co-based cocatalysts, i.e., cobalt iron oxide (CoFeO x ) and cobalt phosphate (CoPi). Interestingly, the electrode modified with CoPi shows improved efficiency and selectivity toward the final product FDCA The source of this enhancement is correlated to the effect of the cocatalyst on the charge carrier dynamics, which is investigated by electrochemical impedance spectroscopy and intensity-modulated photocurrent spectroscopy analysis. In addition, the results of the latter are interpreted through a novel approach called Lasso distribution of relaxation time, revealing that CoPi cocatalyst is effective in the suppression of the recombination processes and in the enhancement of direct hole transfer to TEMPO

Domestic Cat Hepadnavirus: Molecular Epidemiology and Phylogeny in Cats in Hong Kong

Domestic cat hepadnavirus (DCH) is an emerging virus related to the hepatitis B virus (HBV). The pathogenic potential of DCH in cats remains to be established. The molecular prevalence of DCH varies widely in the regions investigated so far. The aim of this study was to determine the prevalence, load, and risk factors for DCH detection among cats in Hong Kong, and to generate molecular and epidemiological data on the DCH strains circulating in cats in Hong Kong. DCH DNA was detected using DCH-specific qPCR in 57/513 (11.1%) residual diagnostic blood samples from owned cats. The median viral load was 8.85 × 103 copies/mL of whole blood (range for the 5th to the 95th percentile, 3.33 × 103 to 2.2 × 105 copies per mL). Two outliers had higher viral loads of 1.88 × 107 copies/mL and 4.90 × 109 copies/mL. DCH was detected in cats from 3 months to 19 years of age. Sex, age, neuter status, breed, or elevated serum alanine aminotransferase were not statistically associated with DCH DNA detection. On phylogenetic analysis based on 12 complete genome sequences, the Hong Kong DCH viruses clustered in Genotype A with viruses from Australia and Asia (clade A1), distinct from viruses from Europe (clade A2). Sequence analysis found that DCH has similar epsilon and direct repeat regions to human HBV, suggesting a conserved method of replication. Based on our findings, the DCH strains circulating in Hong Kong are a continuum of the Asiatic strains

Identification of Novel Astroviruses in the Gastrointestinal Tract of Domestic Cats

Astroviruses, isolated from numerous avian and mammalian species including humans, are commonly associated with enteritis and encephalitis. Two astroviruses have previously been identified in cats, and while definitive evidence is lacking, an association with enteritis is suggested. Using metagenomic next-generation sequencing of viral nucleic acids from faecal samples, we identified two novel feline astroviruses termed Feline astrovirus 3 and 4. These viruses were isolated from healthy shelter-housed kittens (Feline astrovirus 3; 6448 bp) and from a kitten with diarrhoea that was co-infected with Feline parvovirus (Feline astrovirus 4, 6549 bp). Both novel astroviruses shared a genome arrangement of three open reading frames (ORFs) comparable to that of other astroviruses. Phylogenetic analysis of the concatenated ORFs, ORF1a, ORF1b and capsid protein revealed that both viruses were phylogenetically distinct from other feline astroviruses, although their precise evolutionary history could not be accurately determined due to a lack of resolution at key nodes. Large-scale molecular surveillance studies of healthy and diseased cats are needed to determine the pathogenicity of feline astroviruses as single virus infections or in co-infections with other enteric viruses

A gene-wide investigation on polymorphisms in the taste receptor 2R14 (TAS2R14) and susceptibility to colorectal cancer

Background: Molecular sensing in the gastro-intestinal (GI) tract is responsible for the detection of ingested harmful drugs and toxins, thereby genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of the gut in eliminating possible threats to the organism. Although these fundamental control systems have been known for long time, the initial molecular recognition events that sense the chemical composition of the luminal contents of the GI tract have remained elusive. TAS2R14 is one of the better characterized members of the taste receptor family and has several polymorphic variants. Several substances that have been shown to activate TAS2R14 are powerful toxic and carcinogenic agents. Methods: Using a tagging approach we investigated all the common genetic variation of the gene region in relation to colon cancer risk with a case-control study design. This is, at the best of our knowledge also the first report on the allele frequencies of the gene in the Caucasian population. Results: We found no evidence of statistically significant associations between polymorphisms in the TAS2R14 gene and colon cancer risk. Conclusion: In conclusion we can confidently exclude a major role for common polymorphisms of the TAS2R14 gene in colorectal cancer risk in this population, although in this report we had insufficient statistical power to completely exclude the possibility that rare variants of the TAS2R14 might be involved in colorectal cancer risk

Transjugular intrahepatic portosystemic shunt for hepatitis C virus-related portal hypertension after liver transplantation.

hinolfi D, De Simone P, Catalano G, Petruccelli S, Coletti L, Carrai P, Marti J, Tincani G, Cicorelli A, Cioni R, Filipponi F. Transjugular intrahepatic portosystemic shunt for hepatitis C virus-related portal hypertension after liver transplantation. Clin Transplant 2012 DOI: 10.1111/j.1399-0012.2011.01595.x. © 2012 John Wiley & Sons A/S. Abstract:  This is a single center retrospective review of 19 consecutive liver transplant (LT) patients with hepatitis C virus (HCV)-related graft recurrent hepatitis who underwent transjugular intrahepatic portosystemic shunt (TIPS) at a median interval of 21 months (range: 5-50) from LT. Indications were refractory ascites in 11 patients (57.9%), hydrothorax in six (31.6%), and both in two (10.5%). TIPS was successful in 94.7% of cases (18/19) with only one procedure-related mortality (5.3%) owing to sepsis on day 35. At a median follow-up of 23 months (range: one month-nine yr), TIPS allowed for symptoms resolution in 16 patients (84.2%), with ascites resolving in all cases and hydrothorax persisting in 2. Post-TIPS patient survival at six months, one yr, and three yr was 84.2%, 73.7%, and 56.8%, respectively. We compared these results with a control group of 29 patients with HCV recurrence but without unresponsive ascites or hydrothorax. Patients in the control group had better survival than patients undergoing TIPS placement. However, survival of TIPS patients with a MELD score lower than or equal to 12 was similar to that of the control group. We conclude that TIPS may be used to treat complications secondary to HCV

Post-transplant liver graft schistosomiasis in a migrant from sub-saharan africa.

We report a case of post-transplant liver graft infection with Schistosoma spp in a migrant from sub-Saharan Africa transplanted for HBV-related cirrhosis and with undiagnosed schistosomiasis pre-transplantation. The occurrence of tropical diseases in non-endemic areas warrants screening protocols for organ donors and recipients with a history of exposure in endemic areas

Hepadnavirus DNA Is Detected in Canine Blood Samples in Hong Kong but Not in Liver Biopsies of Chronic Hepatitis or Hepatocellular Carcinoma

Chronic hepatitis and hepatocellular carcinoma (HCC) caused by the hepadnavirus hepatitis B virus (HBV) are significant causes of human mortality. A hepatitis-B-like virus infecting cats, domestic cat hepadnavirus (DCH), was reported in 2018. DCH DNA is hepatotropic and detectable in feline blood or serum (3.2 to 12.3%). Detection of HBV DNA has been reported in sera from 10% of free-roaming dogs in Brazil, whereas 6.3% of sera from dogs in Italy tested positive for DCH DNA by real-time quantitative PCR (qPCR). If DCH, HBV, or another hepadnavirus is hepatotropic in dogs, a role for such a virus in the etiology of canine idiopathic chronic hepatitis (CH) or HCC warrants investigation. This study investigated whether DCH DNA could be detected via qPCR in blood from dogs in Hong Kong and also whether liver biopsies from dogs with confirmed idiopathic CH or HCC contained hepadnaviral DNA using two panhepadnavirus conventional PCRs (cPCR) and a DCH-specific cPCR. DCH DNA was amplified from 2 of 501 (0.4%) canine whole-blood DNA samples. A second sample taken 6 or 7 months later from each dog tested negative in DCH qPCR. DNA extracted from 101 liver biopsies from dogs in Hong Kong or the USA, diagnosed by board-certified pathologists as idiopathic CH (n = 47) or HCC (n = 54), tested negative for DCH DNA and also tested negative using panhepadnavirus cPCRs. This study confirms that DCH DNA can be detected in canine blood by qPCR, although at a much lower prevalence than that reported previously. We identified no evidence to support a pathogenic role for a hepadnavirus in canine idiopathic CH or HCC

Feline parvovirus seroprevalence is high in domestic cats from disease outbreak and non‐outbreak regions in Australia

Multiple, epizootic outbreaks of feline panleukopenia (FPL) caused by feline parvovirus (FPV) occurred in eastern Australia between 2014 and 2018. Most affected cats were unvaccinated. We hypothesised that low population immunity was a major driver of re‐emergent FPL. The aim of this study was to (i) determine the prevalence and predictors of seroprotective titres to FPV among shelter‐housed and owned cats, and (ii) compare the prevalence of seroprotection between a region affected and unaffected by FPL outbreaks. FPV antibodies were detected by haemagglutination inhibition assay on sera from 523 cats and titres ≥1:40 were considered protective. Socioeconomic indices based on postcode and census data were included in the risk factor analysis. The prevalence of protective FPV antibody titres was high overall (94.3%), even though only 42% of cats were known to be vaccinated, and was not significantly different between outbreak and non‐outbreak regions. On multivariable logistic regression analysis vaccinated cats were 29.94 times more likely to have protective FPV titres than cats not known to be vaccinated. Cats from postcodes of relatively less socioeconomic disadvantage were 5.93 times more likely to have protective FPV titres. The predictors identified for FPV seroprotective titres indicate targeted vaccination strategies in regions of socioeconomic disadvantage would be beneficial to increase population immunity. The critical level of vaccine coverage required to halt FPV transmission and prevent FPL outbreaks should be determined

Efficacy and safety of combination therapy with everolimus and sorafenib for recurrence of hepatocellular carcinoma after liver transplantation.

Background Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. Methods This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug. Results Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). Conclusions Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival.BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is still associated with a dismal outcome. Combination therapy with everolimus (EVL) and vascular endothelial growth factor inhibitor sorafenib (SORA) is based on the role of both b-Raf and mammalian target of rapamycin/protein kinase B pathways in the pathogenesis of HCC and is being investigated in clinical practice. METHODS: This was a single-center retrospective analysis on LT recipients with unresectable HCC recurrence and undergoing combination therapy with EVL and SORA. Patients were included if they were switched to EVL+SORA at any time after surgery. Primary endpoint was overall survival (OS) after both LT and recurrence, and response to treatment based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) in the intention-to-treat (ITT) population. Secondary analysis was safety of combination therapy with EVL and SORA in the population of patients who received ≥1 dose of the study drug. RESULTS: Seven patients (100% male; median age 53 years [interquartile range (IQR) 9 years]) were considered for analysis. HCC recurrence was diagnosed at a median (IQR) interval since LT of 9 (126) months, and patients were administered EVL+SORA at a median interval since LT of 11 (126) months. Baseline immunosuppression was with tacrolimus (TAC) in 2 patients (28.6%), cyclosporine (CsA) in 2 (28.6%), and EVL monotherapy in 3 (42.8%). At a median (IQR) follow-up of 6.5 (14) months, 5 patients (71.4%) were alive, 4 of them (57.1%) with tumor progression according to the mRECIST criteria. Median (IQR) time to progression was 3.5 (12) months. Two patients died at a median (IQR) follow-up of 5 (1) months owing to tumor progression in 1 patient (14.3%) and sepsis in the other (14.3%). EVL monotherapy was achieved in 6 patients (85.7%), whereas 1patient (14.3%) could not withdraw from calcineurin inhibitor owing to acute rejection. Treatment complications were: hand-foot syndrome in 5 patients (71.4%), hypertension in 1 (14.3%), alopecia in 1 (14.3%), hypothyroidism in 1 (14.3%), diarrhea in 2 (28.6%), pruritus in 1 (14.3%), abdominal pain in 1 (14.3%), rash in 1 (14.3%), asthenia in 3 (42.8%), anorexia in 3 (42.8%), and hoarseness in 2 (28.6%). Adverse events led to temporary SORA discontinuation in 2 patients (28.6%) and to SORA dose reduction in 3 (42.8%). CONCLUSIONS: Treatment of HCC recurrence after LT with a combination regimen of EVL+ SORA is challenging because of SORA-related complications. Longer follow-up periods and larger series are needed to better capture the impact of such combination treatment on tumor progression and patient survival