Clostridium septicum infection of hepatic metastases following alcohol injection: a case report

Clostridium septicum infections are generally associated with gastrointestinal or hematologic malignancies. We report the first case of hepatic metastases infection with Clostridium septicum that followed alcohol injection of liver lesion. Clinicians should consider this possibility in patients with underlying malignancy who present with hepatic abscess, as prompt surgical drainage and empiric antibiotics may be life saving

Glycan and protein analysis of glycoengineered bacterial E. coli vaccines by MALDI-in-source decay FT-ICR mass spectrometry

Bacterial glycoconjugate vaccines have a major role in preventing microbial infections. Immunogenic bacterial glycans, suchas O-antigen polysaccharides, can be recombinantly expressed and combined with specific carrier proteins to produce effective vaccines. O-Antigen polysaccharides are typically polydisperse, and carrier proteins can have multiple glycosylation sites. Consequently, recombinant glycoconjugate vaccines have a high structural heterogeneity, making their characterization challenging. Sincedevelopment and quality control processes rely on such character-ization, novel strategies are needed for faster and informative analysis.Here, we present a novel approach employing minimal samplepreparation and ultrahigh-resolution mass spectrometry analysis forprotein terminal sequencing and characterization of the oligosaccharide repeat units of bacterial glycoconjugate vaccines. Threeglycoconjugate vaccine candidates, obtained from the bioconjugation of the O-antigen polysaccharides fromE. coliserotypes O2,O6A, and O25B with the genetically detoxified exotoxin A fromPseudomonas aeruginosa, were analyzed by MALDI-in-source decay(ISD) FT-ICR MS. Protein and glycan ISD fragment ions were selectively detected using 1,5-diaminonaphtalene and a 2,5-dihydroxybenzoic acid/2-hydroxy-5-methoxybenzoic acid mixture (super-DHB) as a MALDI matrix, respectively. The analysis of protein fragments required the absence of salts in the samples, while the presence of salt was key for the detection of sodiated glycanfragments. MS/MS analysis of O-antigen ISD fragments allowed for the detection of specific repeat unit signatures. The developed strategy requires minute sample amounts, avoids the use of chemical derivatizations, and comes with minimal hands-on time allowing for fast corroboration of key structural features of bacterial glycoconjugate vaccines during early- and late-stage developmentProteomic

Ki67 expression in invasive breast cancer: the use of tissue microarrays compared with whole tissue sections.

BACKGROUND: Although the prognostic value of Ki67 in breast cancer is well documented, using optimal cut-points for patient stratification, reproducibility of the scoring and interpretation of the results remains a matter of debate particularly when using tissue microarrays (TMAs). This study aims to assess Ki67 expression assessed on TMAs and their matched whole tissue sections (WTS). Moreover, whether the cut-off used for WTS is reproducible on TMA in BC molecular classes and the association between Ki67 expression cut-off, assessed on TMAs and WTS, and clinicopathological parameters and patient outcome were tested. METHOD: A large series (n = 707) of primary invasive breast tumours were immunostained for Ki67 using both TMA and WTS and assessed as percentage staining and correlated with each other, clinicopathological parameters and patient outcome. In addition, MKI67 mRNA expression was correlated with Ki67 protein levels on WTS and TMAs in a subset of cases included in the METABRIC study. RESULTS: There was moderate concordance in Ki67 expression between WTS and TMA when analysed as a continuous variable (Intraclass correlation coefficient = 0.61) and low concordance when dichotomised (kappa value = 0.3). TMA showed low levels of Ki67 with mean percentage of expression of 35 and 22% on WTS and TMA, respectively. MKI67 mRNA expression was significantly correlated with protein expression determined on WTS (Spearman Correlation, r = 0.52) and to a lesser extent on TMA (r = 0.34) (p < 0.001). Regarding prediction of patient outcome, statistically significant differences were detected upon stratification of patients with tumours expressing Ki67 at 10, 15, 20, 25 or 30% in TMA. Using TMA, ≥20% Ki67 provided the best prognostic cut-off particularly in triple-negative and HER2-positive classes. CONCLUSION: Ki67 expression in breast cancer can be evaluated using TMA although different cut-points are required to emulate results from WTS. A cut-off of ≥20% for Ki67 expression in BC provides the best prognostic correlations when TMAs are used

Constructing public health policies in post crisis countries: lessons to learn from the associations between free-sugars consumption and diabetes, obesity and dental caries before, during and after sanctions in Iraq.

BACKGROUND: This article aims to provide evidence for an informed public health policy on free-sugar consumption in post-crisis countries. METHODS: Iraq was selected as a case study. A systematic search for published data on the prevalence/incidence of type-2 diabetes, overweight/obesity, dental caries and free-sugar consumption levels in Iraq was conducted using MEDLINE, the Iraqi Academic Scientific journals and relevant international organisations' websites. Comparable data before (1980-1990), during (1991-2002) and after (2003-2015) the United Nations sanctions (UNS) were included. RESULTS: Ten studies were included. Quality scores ranged between 3 and 7/8. Free-sugar consumption decreased dramatically during the UNS (from 50 to 16.3 kg/person/year) and started increasing afterwards (24.1 kg/person/year). Changes in type-2 diabetes, overweight/obesity and caries levels mirrored those of free-sugar consumption. Caries declined markedly during UNS and started increasing afterwards. Comparable data on diabetes and overweight/obesity were only available for the periods during and after the UNS. Both of these conditions started increasing with increased free-sugar consumption after lifting the UNS. CONCLUSIONS: There is a need to develop a public health policy in post-crisis countries to maintain the reduction in free-sugar consumption, and hence promote both general and dental health, by integrating the common risk factor approach into the social determinant framework

Lipoprotein-apheresis reduces circulating microparticles in individuals with familial hypercholesterolemia

Lipoprotein-apheresis (apheresis) removes LDL-cholesterol in patients with severe dyslipidemia. However, reduction is transient, indicating that the long-term cardiovascular benefits of apheresis may not solely be due to LDL removal. Microparticles (MPs) are submicron vesicles released from the plasma membrane of cells. MPs, particularly platelet-derived MPs, are increasingly being linked to the pathogenesis of many diseases. We aimed to characterize the effect of apheresis on MP size, concentration, cellular origin, and fatty acid concentration in individuals with familial hypercholesterolemia (FH). Plasma and MP samples were collected from 12 individuals with FH undergoing routine apheresis. Tunable resistive pulse sensing (np200) and nanoparticle tracking analysis measured a fall in MP concentration (33 and 15%, respectively; P < 0.05) pre- to post-apheresis. Flow cytometry showed MPs were predominantly annexin V positive and of platelet (CD41) origin both pre- (88.9%) and post-apheresis (88.4%). Fatty acid composition of MPs differed from that of plasma, though apheresis affected a similar profile of fatty acids in both compartments, as measured by GC-flame ionization detection. MP concentration was also shown to positively correlate with thrombin generation potential. In conclusion, we show apheresis nonselectively removes annexin V-positive platelet-derived MPs in individuals with FH. These MPs are potent inducers of coagulation and are elevated in CVD; this reduction in pathological MPs could relate to the long-term benefits of apheresis

La comunicazione interculturale e l’approccio comunicativo: dall’idea allo strumento

il saggio si inserisce in un filone di ricerca aperto nel 199 e proseguito con saggi e volumi: in questo caso di descrive e discute la progettazione di un passo fondamentale, dall'elaborazione teorica del modello di riferimento alla traduzione di tale modello in strumento operativo per la consultazione e la didattica

A literature review and survey of childhood pneumonia etiology studies: 2000-2010.

The Pneumonia Etiology Research for Child Health (PERCH) project is the largest multicountry etiology study of childhood pneumonia since the Board on Science and Technology in International Development studies of the 1980s. However, it is not the only recent or ongoing pneumonia etiology study, and even with seven sites, it cannot capture all epidemiologic settings in the developing world. Funding providers, researchers and policymakers rely on the best available evidence to strategically plan programs, new research directions and interventions. We aimed to describe the current landscape of recent pneumonia etiology studies in children under 5 years of age in the developed and developing world, as ascertained by a literature review of relevant studies with data since the year 2000 and a survey of researchers in the field of childhood pneumonia. We collected information on the study population, study design, case definitions, laboratory samples and methods and identified pathogens. A literature review identified 88 studies with child pneumonia etiology results. As of June 2010, our survey of researchers identified an additional 65 ongoing and recently completed child pneumonia etiology studies. This demonstrates the broad existing context into which the PERCH study must be placed. However, the landscape analysis also reveals a multiplicity of case definitions, levels of clinician involvement, facility types, specimen collection, and laboratory techniques. It reinforces the need for the standardization of methods and analyses for present and future pneumonia etiology studies in order to optimize their cumulative potential to accurately describe the microbial causes of childhood pneumonia