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

Abnormal hyperventilation in patients with hepatic cirrhosis: Role of enhanced chemosensitivity to carbon dioxide

BACKGROUND: Patients with hepatic cirrhosis frequently show idiopathic hyperventilation at rest, despite no concomitant cardiopulmonary disease. The aim of the study was to determine whether altered chemosensitivity either to hypoxia or hypercapnia could underlie inappropriate hyperventilation in cirrhotic patients. METHODS: We consecutively recruited 30 biopsy proven cirrhotic patients equally distributed in the three Child's classes A, B and C (age 54±8years, mean±SD). All patients underwent evaluation of chemosensitivity to hypoxia and to hypercapnia and blood sampling for brain natriuretic peptide, norepinephrine and progesterone, besides full clinical characterization. We also recruited 10 age- and gender-matched healthy controls (age 55±7years). RESULTS: Overall, 18 patients (60%) showed an increased chemosensitivity to carbon dioxide (CO(2)), while 8 patients (27%) showed enhanced chemosensitivity to hypoxia. Child's class C patients had lower arterial partial pressure of CO(2) (PaCO(2)), higher rest ventilation, increased chemosensitivity to hypercapnia, plasma level of norepinephrine and serum progesterone levels when compared to class A patients and controls (all p<0.05). Rest ventilation was positively related to pH (R=0.41, p=0.023), chemosensitivity to hypercapnia (R=0.54, p=0.002), and progesterone (R=0.53, p=0.016) and negatively to PaCO(2) (R=0.61, p<0.001), but not to hemoglobin level and chemosensitivity to hypoxia. Chemosensitivity to hypercapnia was positively related to PaCO(2) (R=0.74, p<0.001), serum progesterone (R=0.50, p=0.016), and to plasma norepinephrine (R=0.57, p=0.004). CONCLUSIONS: Enhanced chemosensitivity to hypercapnia was found in more decompensated cirrhotic patients and was associated with sympathetic overactivity and elevated serum progesterone, likely representing a key mechanism underlying the "unexplained" hyperventilation observed in such patients

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

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

Bitter taste receptor polymorphisms and human aging.

Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p = 0.001) with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics

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

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

Feline calicivirus virulent systemic disease: Clinical epidemiology, analysis of viral isolates and in vitro efficacy of novel antivirals in australian outbreaks

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCVVSD viruses is incompletely understood, and antivirals for FCV-VSD have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2′-C-methylcytidine (2CMC) and NITD008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCVURTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino-acid residues from the hypervariable E region of the capsid in the cultured viruses did not support the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose–response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4–0.6 µM, TI = 21; 2CMC EC50, 2.7–5.3 µM, TI &gt; 18; NITD-008, 0.5 to 0.9 µM, TI &gt; 111. Investigation of these antivirals for the treatment of FCV-VSD is warranted

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