4D-Analysis of Left Ventricular Heart Cycle Using Procrustes Motion Analysis

The aim of this study is to investigate human left ventricular heart morphological changes in time among 17 healthy subjects. Preliminarily, 2 patients with volumetric overload due to aortic insufficiency were added to our analyses. We propose a special strategy to compare the shape, orientation and size of cardiac cycle’s morphological trajectories in time. We used 3D data obtained by Speckle Tracking Echocardiography in order to detect semi-automated and homologous landmarks clouds as proxies of left ventricular heart morphology. An extended Geometric Morphometrics toolkit in order to distinguish between intra- and inter-individual shape variations was used. Shape of trajectories with inter-individual variation were compared under the assumption that trajectories attributes, estimated at electrophysiologically homologous times are expressions of left ventricular heart function. We found that shape analysis as commonly applied in Geometric Morphometrics studies fails in identifying a proper morpho-space to compare the shape of morphological trajectories in time. To overcome this problem, we performed a special type of Riemannian Parallel Transport, called “linear shift”. Whereas the two patients with aortic insufficiency were not differentiated in the static shape analysis from the healthy subjects, they set apart significantly in the analyses of motion trajectory’s shape and orientation. We found that in healthy subjects, the variations due to inter-individual morphological differences were not related to shape and orientation of morphological trajectories. Principal Component Analysis showed that volumetric contraction, torsion and twist are differently distributed on different axes. Moreover, global shape change appeared to be more correlated with endocardial shape change than with the epicardial one. Finally, the total shape variation occurring among different subjects was significantly larger than that observable across properly defined morphological trajectories.     

Liver as a Source for Thymidine Phosphorylase Replacement in Mitochondrial Neurogastrointestinal Encephalomyopathy

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive mitochondrial disease associated with mutations in the nuclear TYMP gene. As a result, the thymidine phosphorylase (TP) enzyme activity is markedly reduced leading to toxic accumulation of thymidine and therefore altered mitochondrial DNA. MNGIE is characterized by severe gastrointestinal dysmotility, neurological impairment, reduced life expectancy and poor quality of life. There are limited therapeutic options for MNGIE. In the attempt to restore TP activity, allogenic hematopoietic stem cell transplantation has been used as cellular source of TP. The results of this approach on ∼20 MNGIE patients showed gastrointestinal and neurological improvement, although the 5-year mortality rate is about 70%. In this study we tested whether the liver may serve as an alternative source of TP. We investigated 11 patients (7M; 35–55 years) who underwent hepatic resection for focal disorders. Margins of normal liver tissue were processed to identify, quantify and localize the TP protein by Western Blot, ELISA, and immunohistochemistry, and to evaluate TYMP mRNA expression by qPCR. Western Blot identified TP in liver with a TP/GAPDH ratio of 0.9±0.5. ELISA estimated TP content as 0.5±0.07 ng/μg of total protein. TP was identified in both nuclei and cytoplasm of hepatocytes and sinusoidal lining cells. Finally, TYMP mRNA was expressed in the liver. Overall, our study demonstrates that the liver is an important source of TP. Orthotopic liver transplantation may be considered as a therapeutic alternative for MNGIE patients.     

Risk of Trypanosoma cruzi infection among travellers visiting friends and relatives to continental Latin America

BackgroundChagas disease (CD) is regarded as a possible risk for travellers to endemic areas of continental Latin America (LA). The aim of the study is to determine the risk of Trypanosoma cruzi (TC) infection among travellers to CD endemic areas and to identify risk factors for acquiring TC infection.Methods/Principal findingWe designed a multicenter cross-sectional study among travellers in Spain (Badalona, Barcelona and Madrid). All available adults with laboratory confirmed proof of absence of TC infection from January 2012 to December 2015 were contacted. Participants referring a trip to LA after the negative TC screening were offered to participate. We performed a standardized questionnaire of travel related factors and measurement of TC antibodies in serum. A total of 971 participants with baseline negative TC serology were selected from the microbiology records. After excluding participants not meeting inclusion criteria, eighty participants were selected. Sixty three (78.8%) were female, and the median age was 38 (IQR 34–47) years. The reason to travel was visiting friends and relatives in 98.8% of the participants. The median duration of travel was 40 (IQR 30–60) days, with 4911 participants-day of exposure. Seventy seven cases (96.25%) participants had two negative TC serology tests after the travel, two cases (2.5%) had discordant serology results (considered false positive results) and one case was infected before travelling to LA. According to our data, the upper limit of the 95% confidence interval of the incidence rate of TC acquisition in travellers is 0.8 per 1000 participant-days.Conclusions/SignificanceAmong 79 non-CD travellers to TC endemic areas, we found no cases of newly acquired TC infection. The incidence rate of TC acquisition in travellers to endemic countries is less than or equal to 0.8 per 1000 traveller-days.     

An integrated pan‐tropical biomass map using multiple reference datasets

We combined two existing datasets of vegetation aboveground biomass (AGB) (Proceedings of the National Academy of Sciences of the United States of America, 108 , 2011, 9899; Nature Climate Change, 2 , 2012, 182) into a pan‐tropical AGB map at 1‐km resolution using an independent reference dataset of field observations and locally calibrated high‐resolution biomass maps, harmonized and upscaled to 14 477 1‐km AGB estimates. Our data fusion approach uses bias removal and weighted linear averaging that incorporates and spatializes the biomass patterns indicated by the reference data. The method was applied independently in areas (strata) with homogeneous error patterns of the input (Saatchi and Baccini) maps, which were estimated from the reference data and additional covariates. Based on the fused map, we estimated AGB stock for the tropics (23.4 N–23.4 S) of 375 Pg dry mass, 9–18% lower than the Saatchi and Baccini estimates. The fused map also showed differing spatial patterns of AGB over large areas, with higher AGB density in the dense forest areas in the Congo basin, Eastern Amazon and South‐East Asia, and lower values in Central America and in most dry vegetation areas of Africa than either of the input maps. The validation exercise, based on 2118 estimates from the reference dataset not used in the fusion process, showed that the fused map had a RMSE 15–21% lower than that of the input maps and, most importantly, nearly unbiased estimates (mean bias 5 Mg dry mass ha^?1 vs. 21 and 28 Mg ha^?1 for the input maps). The fusion method can be applied at any scale including the policy‐relevant national level, where it can provide improved biomass estimates by integrating existing regional biomass maps as input maps and additional, country‐specific reference datasets.     

Faecal nutritional indicators in relation to the comparative population performance of sable antelope and other grazers

In the Kruger National Park, sable antelope underwent a substantial decline in abundance after 1987. Our study investigated whether forage quality as reflected by faecal nutrient contents could be restricting population recovery. Faecal samples were collected from sable, zebra and buffalo in one study area and from sable only in a second study area with higher mean rainfall, during the dry seasons of two successive years. Faecal samples were analysed for nitrogen, phosphorus, sodium and crude fibre. Faecal nitrogen and phosphorus levels were similar for sable and buffalo and remained around or slightly above putative maintenance levels, but were higher than shown by nonruminant zebra. Faecal sodium levels were substantially lower for sable than for the other two grazers. In the wetter study area, faecal nitrogen levels for sable herds fell below the minimum maintenance level throughout the dry season in the drier year. Although faecal nutrient levels for sable appeared only marginally limiting under the conditions that prevailed during the study, malnutrition could have contributed to the population decline by sable during a persistently low‐rainfall period.     

Extracellular enzymatic activities in Cryptococcus neoformans strains isolated from AIDS patients in different countries

Three hundred and ten Cryptococcus neoformans strains isolated from AIDS patients in five different countries (151 from Brazil, 23 from Italy, 28 from Spain, 104 from Thailand and four from Turkey) were tested by the API-ZYM kit to detect their extracellular enzymatic activity. The enzymes esterase (C4) (no 3), esterase lipase (C8) (no 4), leucine arylamidase (no 6) and acid phosphatase (no 11) were commonly positive in most of the strains (more than 95%). These enzymes could be considered a useful tool not only for C. neoformans identification, but in particular for their possible relationship to new C. neoformans virulence factors and also for epidemiological research. Interestingly, it is also the high positive percentage of alpha-glucosidase and beta-glucosidase detected in all isolates. The serotype A was the most predominant serotype in all countries, except for Italy where the serotype D was predominant. Further studies are needed to draw a clear correlation between the API-ZYM profile and serotype.     

Structure-based design of isoquinoline-5-sulfonamide inhibitors of protein kinase B

Structure-based drug design of novel isoquinoline-5-sulfonamide inhibitors of PKB as potential antitumour agents was investigated. Constrained pyrrolidine analogues that mimicked the bound conformation of linear prototypes were identified and investigated by co-crystal structure determinations with the related protein PKA. Detailed variation in the binding modes between inhibitors with similar overall conformations was observed. Potent PKB inhibitors from this series inhibited GSK3beta phosphorylation in cellular assays, consistent with inhibition of PKB kinase activity in cells.     

Distribution of mosquito species in areas with high and low incidence of classic Kaposi's sarcoma and seroprevalence for HHV-8

The 'promoter-arthropod' hypothesis, which postulates that exposure to the bites of certain species of haematophagous arthropods is an environmental risk cofactor linked to human herpes virus 8 (HHV-8) and Kaposi's sarcoma, was investigated in the Po River valley, northern Italy. The presence and density of adult female mosquitoes (Diptera: Culicidae) was determined by CDC light trap catches in two adjacent districts, at variance with respect to Kaposi's sarcoma incidence and HHV-8 seroprevalence. A total of 3910 specimens belonging to 11 species was collected in 34 rural sites (six municipalities) representative of the two districts. Five of these species are considered to be possible 'promoters' because of the irritation their bites cause humans: Aedes vexans (Meigen) and Ae. caspius (Pallas) (87% of sampled promoters), Culex modestus Ficalbi, Culiseta annulata (Schrank) and Coquillettidia richiardii (Ficalbi). Six are probable 'non-promoters': Cx. pipiens s.l., Cx. martinii Medschid, Anopheles claviger (Meigen), An. maculipennis s.l., An. plumbeus Stephens and Uranotaenia unguiculata Edwards. The density of promoters by site was correlated with the incidence rates of Kaposi's sarcoma at the district level (Pearson's r = 0.33, P = 0.06) and at the municipal level (r = 0.50, P< 0.01). Similar correlations emerged for non-promoters (r = 0.48, P< 0.01 and r = 0.42, P = 0.01, respectively). The density of promoters was higher than that of non-promoters in sites with livestock (odds ratio, OR = 2.8, 95% CI 2.2-3.6) and in municipalities with Kaposi's sarcoma cases (OR = 2.5, 95% CI 1.7-3.5). The study provides additional evidence of the association between the density of some mosquito species and Kaposi's sarcoma.