E2 strengths and transition radii difference of one-phonon 2+ states of 92Zr from electron scattering at low momentum transfer

Background: Mixed-symmetry 2+ states in vibrational nuclei are characterized by a sign change between dominant proton and neutron valence-shell components with respect to the fully symmetric 2+ state. The sign can be measured by a decomposition of proton and neutron transition radii with a combination of inelastic electron and hadron scattering [C. Walz et al., Phys. Rev. Lett. 106, 062501 (2011)]. For the case of 92Zr, a difference could be experimentally established for the neutron components, while about equal proton transition radii were indicated by the data. Method: Differential cross sections for the excitation of one-phonon 2+ and 3- states in 92Zr have been measured with the (e,e') reaction at the S-DALINAC in a momentum transfer range q = 0.3-0.6 fm^(-1). Results: Transition strengths B(E2;2+_1 -> 0+_1) = 6.18(23), B(E2; 2+_2 -> 0+_1) = 3.31(10) and B(E3; 3-_1 -> 0+_1) = 18.4(11) Weisskopf units are determined from a comparison of the experimental cross sections to quasiparticle-phonon model (QPM) calculations. It is shown that a model-independent plane wave Born approximation (PWBA) analysis can fix the ratio of B(E2) transition strengths to the 2+_(1,2) states with a precision of about 1%. The method furthermore allows to extract their proton transition radii difference. With the present data -0.12(51) fm is obtained. Conclusions: Electron scattering at low momentum transfers can provide information on transition radii differences of one-phonon 2+ states even in heavy nuclei. Proton transition radii for the 2+_(1,2) states in 92Zr are found to be identical within uncertainties. The g.s. transition probability for the mixed-symmetry state can be determined with high precision limited only by the available experimental information on the B(E2; 2+_1 -> 0+_1) value.Comment: 14 pages, 5 figures, submitted to Phys. Rev. C, revised manuscrip

Imbalanced Folate and Vitamin B12 in the Third Trimester of Pregnancy and its Association with Birthweight and Child Growth up to 2 Years

Scope: Folic acid supplementation during pregnancy may lead to an imbalance when vitamin B12 intake is low (folate trap) and may affect child’s growth. Methods: The authors study the association between third trimester maternal intakes of folate and B12 and birthweight and postnatal growth of 2632 infants from the KOALA Birth Cohort Study. Plasma vitamin biomarkers are measured in 1219 women. Results: Imbalanced total intakes (folate > 430 µg day−1 combined with B12 < 5.5 µg day−1) are not associated with birthweight [ adj (95% CI) = –14.87 (–68.87, 39.13)] compared with high intakes of both. Imbalanced intake is associated with a lower z score of weight at 1–2 years [ adj = –0.14 (–0.25, –0.03)]. Having red blood cell folate > 745 nmol L−1 and plasma B12 < 172 pmol L−1 is not associated with birthweight [ adj = –7.10 (–97.90, 83.71) g]. Maternal dietary B12 intake [ adj = –9.5 (–15.6, –3.3)] and plasma methylmalonic acid [ adj = 234 (43, 426)] are associated with birthweight. Conclusion: Low maternal dietary B12 intake and elevated methylmalonic acid rather than imbalanced vitamins are associated with higher birthweight, suggesting that low maternal B12 can predispose the infants for later obesity

OHMI: The Ontology of Host-Microbiome Interactions

Host-microbiome interactions (HMIs) are critical for the modulation of biological processes and are associated with several diseases, and extensive HMI studies have generated large amounts of data. We propose that the logical representation of the knowledge derived from these data and the standardized representation of experimental variables and processes can foster integration of data and reproducibility of experiments and thereby further HMI knowledge discovery. A community-based Ontology of Host-Microbiome Interactions (OHMI) was developed following the OBO Foundry principles. OHMI leverages established ontologies to create logically structured representations of microbiomes, microbial taxonomy, host species, host anatomical entities, and HMIs under different conditions and associated study protocols and types of data analysis and experimental results

Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy.

Patients with cancer who developed severe, grade 3 or 4 immune-related adverse events (irAEs) during therapy with immune checkpoint inhibitors are at risk for developing severe toxicities again on rechallenge with checkpoint inhibitors. Consequently, medical oncologists and multidisciplinary teams are hesitant to retreat in this scenario, despite the fact that a number of patients may derive clinical benefit from this approach. Balancing such clinical benefit and treatment-related toxicities for each patient is becoming increasingly challenging as more and more patients with cancer are being treated with checkpoint inhibitors. In this manuscript, we provide an extensive overview of the relevant literature on retreatment after toxicity, and suggest prophylactic approaches to minimize the risk of severe irAE following rechallenge with immune checkpoint blockade, since treatment may be lifesaving in a number of occasions

The role of biofactors in the prevention and treatment of age‐related diseases

The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age‐related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age‐related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age‐related diseases, and ultimately of mortality in the older population. These biofactors can be a cost‐effective strategy to prevent or, in some cases, even treat age‐related diseases. Examples reviewed herein include omega‐3 fatty acids and dietary fiber for the prevention of CVD, α‐tocopherol (vitamin E) for the treatment of biopsy‐proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α‐lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age‐related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors , we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature

Diabetes and baseline glucose are associated with inflammation, left ventricular function and short- and long-term outcome in acute coronary syndromes: role of the novel biomarker Cyr 61.

Hyperglycemia in the setting of an acute coronary syndrome (ACS) impacts short term outcomes, but little is known about longer term effects. We therefore designed this study to firstly determine the association between hyperglycemia and short term and longer term outcomes in patients presenting with ACS and secondly evaluate the prognostic role of diabetes, body mass index (BMI) and the novel biomarker Cyr61 on outcomes. The prospective Special Program University Medicine-Acute Coronary Syndrome (SPUM-ACS) cohort enrolled 2168 patients with ACS between December 2009 and October 2012, of which 2034 underwent PCI (93.8%). Patients were followed up for 12 months. Events were independently adjudicated by three experienced cardiologists. Participants were recruited from four tertiary hospitals in Switzerland: Zurich, Geneva, Lausanne and Bern. Participants presenting with acute coronary syndromes and who underwent coronary angiography were included in the analysis. Patients were grouped according to history of diabetes (or HbA1c greater than 6%), baseline blood sugar level (BSL; &lt; 6, 6-11.1 and &gt; 11.1 mmol/L) and body mass index (BMI). The primary outcome was major adverse cardiac events (MACE) which was a composite of myocardial infarction, stroke and all-cause death. Secondary outcomes included the individual components of the primary endpoint, revascularisations, bleeding events (BARC classification) and cerebrovascular events (ischaemic or haemorrhagic stroke or TIA). Patients with hyperglycemia, i.e. BSL ≥ 11.1 mmol/L, had higher levels of C-reactive protein (CRP), white blood cell count (WBC), creatinine kinase (CK), higher heart rates and lower left ventricular ejection fraction (LVEF) and increased N-terminal pro-brain natriuretic peptide. At 30 days and 12 months, those with BSL ≥ 11.1 mmol/L had more MACE and death compared to those with BSL &lt; 6.0 mmol/L or 6.0-11.1 mmol/L (HR-ratio 4.78 and 6.6; p &lt; 0.001). The novel biomarker Cyr61 strongly associated with high BSL and STEMI and was independently associated with 1 year outcomes (HR 2.22; 95% CI 1.33-3.72; Tertile 3 vs. Tertile 1). In this large, prospective, independently adjudicated cohort of in all comers ACS patients undergoing PCI, both a history of diabetes and elevated entry glucose was associated with inflammation and increased risk of MACE both at short and long-term. The mediators might involve increased sympathetic activation, inflammation and ischemia as reflected by elevated Cyr61 levels leading to larger levels of troponin and lower LVEF. Trial registration Clinical Trial Registration Number: NCT01000701. Registered October 23, 2009

Acinic cell carcinoma in pregnancy: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>We report an observational study on the etiology and recurrence of acinic cell carcinoma of the parotid gland that seemed to be related to pregnancy. The medical literature has never reported such an association; therefore, our case report is probably the first to mention this observation.</p> <p>Case presentation</p> <p>This report is of a 25-year-old Arabic female patient from the United Arab Emirates, who, during her first pregnancy, developed acinic cell carcinoma of the right parotid gland that was managed with surgical excision in the form of superficial parotidectomy. During her second pregnancy, which occurred four years later, she had a recurrence of the same malignant neoplasm associated with ipsilateral malignant cervical lymphadenopathy. The patient was managed with total parotidectomy and neck dissection, as well as postoperative adjuvant radiotherapy. Our observation on this particular case of acinic cell carcinoma is that the initial onset of her neoplasm was during her first pregnancy, and the recurrence of the same malignant disease was during a subsequent pregnancy. This chronologic association raised our suspicion that there might be a possible etiologic effect of pregnancy or its associated hormonal or physiologic changes or both on the pathogenesis or etiology of acinic cell carcinoma.</p> <p>Conclusion</p> <p>Some association might exist between pregnancy and the pathogenesis or etiology of acinic cell carcinoma.</p

Identification of the Rheumatoid Arthritis Shared Epitope Binding Site on Calreticulin

Background: The rheumatoid arthritis (RA) shared epitope (SE), a major risk factor for severe disease, is a five amino acid motif in the third allelic hypervariable region of the HLA-DRb chain. The molecular mechanisms by which the SE affects susceptibility to – and severity of- RA are unknown. We have recently demonstrated that the SE acts as a ligand that interacts with cell surface calreticulin (CRT) and activates innate immune signaling. In order to better understand the molecular basis of SE-RA association, here we have undertaken to map the SE binding site on CRT. Principal Findings: Surface plasmon resonance (SPR) experiments with domain deletion mutants suggested that the SE binding site is located in the P-domain of CRT. The role of this domain as a SE-binding region was further confirmed by a sulfosuccinimidyl-2-[6-(biotinamido)-2-(p-azido-benzamido) hexanoamido] ethyl-1,3-dithiopropionate (sulfo-SBED) photoactive cross-linking method. In silico analysis of docking interactions between a conformationally intact SE ligand and the CRT P-domain predicted the region within amino acid residues 217–224 as a potential SE binding site. Site-directed mutagenesis demonstrated involvement of residues Glu 217 and Glu 223- and to a lesser extent residue Asp 220- in cell-free SPR-based binding and signal transduction assays. Significance: We have characterized here the molecular basis of a novel ligand-receptor interaction between the SE and CRT. The interaction represents a structurally and functionally well-defined example of cross talk between the adaptive an