In this work the production of auto-assembled nanoparticles obtained by the mixing of chitosan and lecithin is presented. The size and surface charge of the nanoparticles were studied as function of ...the weight ratio between components, the viscosity of the polysaccharide and the pH of the colloidal suspension.
In order to elucidate the structure of nanoparticles, micro-FT-IR and elastic neutron scattering experiments have been performed. Results evidenced a strong electrostatic interaction between components and a structure that is neither that of homogeneous spheres nor of coated unilamellar vesicles. Preliminary encapsulation experiments with progesterone, as model lipophilic drug, showed good encapsulation efficiencies.
The Short Physical Performance Battery (SPPB) is a well-established tool to assess lower extremity physical performance status. Its predictive ability for all-cause mortality has been sparsely ...reported, but with conflicting results in different subsets of participants. The aim of this study was to perform a meta-analysis investigating the relationship between SPPB score and all-cause mortality.
Articles were searched in MEDLINE, the Cochrane Library, Google Scholar, and BioMed Central between July and September 2015 and updated in January 2016. Inclusion criteria were observational studies; >50 participants; stratification of population according to SPPB value; data on all-cause mortality; English language publications. Twenty-four articles were selected from available evidence. Data of interest (i.e., clinical characteristics, information after stratification of the sample into four SPPB groups 0-3, 4-6, 7-9, 10-12) were retrieved from the articles and/or obtained by the study authors. The odds ratio (OR) and/or hazard ratio (HR) was obtained for all-cause mortality according to SPPB category (with SPPB scores 10-12 considered as reference) with adjustment for age, sex, and body mass index.
Standardized data were obtained for 17 studies (n = 16,534, mean age 76 ± 3 years). As compared to SPPB scores 10-12, values of 0-3 (OR 3.25, 95%CI 2.86-3.79), 4-6 (OR 2.14, 95%CI 1.92-2.39), and 7-9 (OR 1.50, 95%CI 1.32-1.71) were each associated with an increased risk of all-cause mortality. The association between poor performance on SPPB and all-cause mortality remained highly consistent independent of follow-up length, subsets of participants, geographic area, and age of the population. Random effects meta-regression showed that OR for all-cause mortality with SPPB values 7-9 was higher in the younger population, diabetics, and men.
An SPPB score lower than 10 is predictive of all-cause mortality. The systematic implementation of the SPPB in clinical practice settings may provide useful prognostic information about the risk of all-cause mortality. Moreover, the SPPB could be used as a surrogate endpoint of all-cause mortality in trials needing to quantify benefit and health improvements of specific treatments or rehabilitation programs. The study protocol was published on PROSPERO (CRD42015024916).
The protein-only hypothesis predicts that infectious mammalian prions are composed solely of PrPSc, a misfolded conformer of the normal prion protein, PrPC. However, protein-only PrPSc preparations ...lack significant levels of prion infectivity, leading to the alternative hypothesis that cofactor molecules are required to form infectious prions. Here, we show that prions with parental strain properties and full specific infectivity can be restored from protein-only PrPSc in vitro. The restoration reaction is rapid, potent, and requires bank vole PrPC substrate, post-translational modifications, and cofactor molecules. To our knowledge, this represents the first report in which the essential properties of an infectious mammalian prion have been restored from pure PrP without adaptation. These findings provide evidence for a unified hypothesis of prion infectivity in which the global structure of protein-only PrPSc accurately stores latent infectious and strain information, but cofactor molecules control a reversible switch that unmasks biological infectivity.
We revisit leptogenesis in the minimal nonsupersymmetric type I seesaw mechanism with two right-handed (RH) neutrinos, including flavor effects and allowing both RH neutrinos N sub(1) and N sub(2) to ...contribute, rather than just the lightest RH neutrino N sub(1) that has hitherto been considered. By performing scans over parameter space in terms of the single complex angle z of the orthogonal matrix R, for a range of leptonic mixing parameters, we find that in regions around z ~ + or -pi/2, for the case of a normal mass hierarchy, the N sub(2) contribution can dominate the contribution to leptogenesis, allowing the lightest RH neutrino mass to be decreased by about an order of magnitude in these regions, down to M sub(1) ~ 1.3 x 10 super(11) GeV for vanishing initial N sub(2)-abundance, with the numerical results supported by analytic estimates. We show that the regions around z ~ + or -pi/2 correspond to light sequential dominance, so the new results in this paper may be relevant to unified model building.
The majority of emerging infectious diseases are zoonoses, most of which are classified as "neglected". By affecting both humans and animals, zoonoses pose a dual burden. The disability-adjusted life ...year (DALY) metric quantifies human health burden using mortality and morbidity. This review aims to describe and analyze the current state of evidence on the burden of neglected zoonotic diseases (NZDs) and start a discussion on the current understanding of the global burden of NZDs. We identified 26 priority NZDs through consulting the CDC One Health Zoonotic Disease Prioritization Exercise, the Joint External Evaluation reports, and the WHO roadmap for NTDs. A systematic review of global and national burden of disease (BoD) studies for these priority NZDs was conducted using pre-selected databases. Data on diseases, location and DALYs were extracted for each eligible study. A total of 1887 records were screened, resulting in 72 eligible studies (58 national or sub-national, 12 global, and 2 regional studies). The highest number of BoD studies was found for non-typhoidal salmonellosis (23), whereas no estimates were found for West Nile, Marburg and Lassa fever. Geographically, the highest number of studies were found in the Netherlands (11), China (5) and Iran (4). The number of BoD studies retrieved mismatched the perceived importance in national prioritization exercises. For example, anthrax was considered a priority NZD in 73 countries, but only one national estimate was retrieved. By summing the available global estimates, these diseases would cause at least 10 million DALYs in total. The burden of NZDs at the global level remains scattered, and trends were challenging to identify. There are several priority NZDs for which no burden estimates exist, and the number of BoD studies does not reflect national disease priorities. To have complete and consistent estimates of the global burden of NZDs, these diseases should be integrated into larger global BoD initiatives.
Key messages
* There is a mismatched between the estimated retrieved in the search and the perception of the importance of these disease. This amplify the need for a comprehensive program.
* No complete list of zoonoses exist, and the definition used is vague. A stricter definition of zoonoses and what defines them will help provide a clear view of dealing with and controlling them.
Background
Foodborne and zoonotic diseases such as brucellosis present many challenges to public health and economic welfare. Increasingly, researchers and public health institutes use ...disability-adjusted life years (DALYs) to generate a comprehensive comparison of the population health impact of these conditions. DALY calculations entail several methodological choices and assumptions, with data gaps and uncertainties to accommodate. The following review identifies existing brucellosis burden studies and analyses their methodological choices and assumptions.
Methods/Findings
A systematic search for brucellosis burden calculations was conducted in pre-selected international and grey literature databases. Using a standardized reporting framework, we evaluated each estimate on a variety of key methodological assumptions necessary to compute a DALY. One study reported estimates at the global level, the rest (13) at national or subnational. Most studies retrieved brucellosis epidemiological data from administrative registries. Incidence data were often estimated based on laboratory-confirmed tests. Not all studies included mortality estimates (YLLs) in their assessments due to the lack of data or the assumption that brucellosis is not a fatal disease. Only two studies used a model with variable health states and corresponding disability weights. The rest used a simplified singular health state approach. Wide variation was seen in the duration chosen for brucellosis, ranging from 2 weeks to 4.5 years, irrespective of whether a chronic state was included.
Conclusions
Available brucellosis burden assessments vary widely in their methodology and assumptions. Further research is needed to characterize better the total clinical course of brucellosis and estimate case-fatality rate. In addition, reporting of methodological choices should be improved to enhance transparency and comparability of estimates. These steps will increase the value of these estimates for policymakers.
Key messages
* Inconsistencies in reporting methods and assumptions are found, which hinder transparency and understanding of the methodological choices and the reuse of estimates for prioritization purposes.
* Thus, there is a need for a more standardized reporting system for DALY estimates, which could resemble a checklist that reports the methodological choices and assumptions.
The symptoms of prion infection can take years or decades to manifest following the initial exposure. Molecular markers of prion disease include accumulation of the misfolded prion protein (PrPSc), ...which is derived from its cellular precursor (PrPC), as well as downregulation of the PrP-like Shadoo (Sho) glycoprotein. Given the overlapping cellular environments for PrPC and Sho, we inferred that PrPC levels might also be altered as part of a host response during prion infection. Using rodent models, we found that, in addition to changes in PrPC glycosylation and proteolytic processing, net reductions in PrPC occur in a wide range of prion diseases, including sheep scrapie, human Creutzfeldt-Jakob disease, and cervid chronic wasting disease. The reduction in PrPC results in decreased prion replication, as measured by the protein misfolding cyclic amplification technique for generating PrPSc in vitro. While PrPC downregulation is not discernible in animals with unusually short incubation periods and high PrPC expression, slowly evolving prion infections exhibit downregulation of the PrPC substrate required for new PrPSc synthesis and as a receptor for pathogenic signaling. Our data reveal PrPC downregulation as a previously unappreciated element of disease pathogenesis that defines the extensive, presymptomatic period for many prion strains.
The genus Hystrix includes eight species of porcupines distributed in Eurasia and Africa, across a broad latitudinal gradient. Our aim was to assess whether porcupine skulls: (1) allow for a reliable ...interspecific distinction; (2) change in size proportionally with body size; (3) follow the Bergmann's rule. We measured 235 Hystrix skulls from museums and private collections. We tested for differences in skull size and we assessed whether variability in skull shape allows species recognition through a multivariate approach. All Hystrix species considered could be reliably identified by skull shape. Skull size was correlated with body size and species differed in skull shape and size, with skulls of Hystrix javanica and Hystrix africaeaustralis being respectively the smallest and the largest ones. Within Hystrix cristata, the Mediterranean and the sub‐Saharan clades differed for both skull size and shape. Using skull size, we could distinguish among African, mainland Italian and Sicilian populations. Skull size of this species decreased in size for increasing latitude values, contrary to prediction by the Bergmann's rule. Such latitudinal pattern may depend on the adaption of H. cristata to Equatorial African conditions, where the species evolved. In Italy (where H. cristata was introduced in the VI Century AD) and in North Africa, a smaller body size may be due to the local climate, or to a ‘founder effect’.
In our work, we aimed to assess whether porcupine skulls fit the Bergmann’s rule. We measured 235 Hystrix skulls of 5 species from museums and private collections. The opposite pattern of the Bergmann’s rule was observed in Hystrix cristata may be due to the fact that this species evolved in Equatorial Africa. In Italy (where introduced) and in North Africa as well, a smaller body‐size would occur because of unsuitable climates or as a result of the founder effect.
In order to assess the susceptibility of bank voles to chronic wasting disease (CWD), we inoculated voles carrying isoleucine or methionine at codon 109 (Bv109I and Bv109M, respectively) with CWD ...isolates from elk, mule deer and white-tailed deer. Efficient transmission rate (100%) was observed with mean survival times ranging from 156 to 281 days post inoculation. Subsequent passages in Bv109I allowed us to isolate from all CWD sources the same vole-adapted CWD strain (Bv(109I)CWD), typified by unprecedented short incubation times of 25-28 days and survival times of ∼35 days. Neuropathological and molecular characterisation of Bv(109I)CWD showed that the classical features of mammalian prion diseases were all recapitulated in less than one month after intracerebral inoculation. Bv(109I)CWD was characterised by a mild and discrete distribution of spongiosis and relatively low levels of protease-resistant PrP(Sc) (PrP(res)) in the same brain regions. Despite the low PrP(res) levels and the short time lapse available for its accumulation, end-point titration revealed that brains from terminally-ill voles contained up to 10(8,4) i.c. ID50 infectious units per gram. Bv(109I)CWD was efficiently replicated by protein misfolding cyclic amplification (PMCA) and the infectivity faithfully generated in vitro, as demonstrated by the preservation of the peculiar Bv(109I)CWD strain features on re-isolation in Bv109I. Overall, we provide evidence that the same CWD strain was isolated in Bv109I from the three-cervid species. Bv(109I)CWD showed unique characteristics of "virulence", low PrP(res) accumulation and high infectivity, thus providing exceptional opportunities to improve basic knowledge of the relationship between PrP(Sc), neurodegeneration and infectivity.
It has been shown previously that ovine prion protein (PrP(C)) renders rabbit epithelial RK13 cells permissive to the multiplication of ovine prions, thus providing evidence that species barriers can ...be crossed in cultured cells through the expression of a relevant PrP(C). The present study significantly extended this observation by showing that mouse and bank vole prions can be propagated in RK13 cells that express the corresponding PrP(C). Importantly, the respective molecular patterns of abnormal PrP (PrP(res)) and, where examined, the neuropathological features of the infecting strains appeared to be maintained during the propagation in cell culture. These findings indicate that RK13 cells can be genetically engineered to replicate prion strains faithfully from different species. Such an approach may facilitate investigations of the molecular basis of strain identity and prion diversity.
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