Uncontrolled allergic rhinoconjunctivitis to pollen and a new oral allergy syndrome with fresh fruits: should we take a top down or a bottom up approach?

European Acad Allergol & Clin Immunolinfo:eu-repo/semantics/publishedVersio

Atypical form of acute myocardial infarction with tamponade

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2019.Background: Nowadays it is well recognized that the absence of obstructive coronary artery disease in a patient presenting with symptoms suggestive of ischemia and ST-segment alterations does not preclude an atherothrombotic etiology. CMR is an essential method for the investigation of Myocardial infarction (MI) with non obstructive coronary artery disease (MINOCA). Clinical Case: A 66 years-old female patient was referred after an episode of acute oppressive chest pain, nausea and hypersudorese, followed by syncope. She had a previous medical history of rheumatoid arthritis, under immunosuppression, occlusion of the cilioretinal artery, hypertension and dyslipidemia. On admission she was hypotensive (80/60mmHg). The ECG showed sinus rhythm and mild ST depression in V2-V3 leads, and the echocardiogram a small circumferential pericardial effusion (10mm) with signs of hemodynamic compromise. The blood tests documented a slight leukocytosis and an elevated troponin (hs-TnT 619ng/L).info:eu-repo/semantics/publishedVersio

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects

Left ventricular systolic dysfunction in Marfan syndrome is related to aortic distensibility

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2019.Background: The cardiovascular involvement in Marfan syndrome (MS) is characterized mainly by dilatation and reduced distensibility of the ascending aorta. Left ventricular (LV) dysfunction has been detected in MS and a primary cardiomyopathy has been suggested but the pathophysiology is unclear. The purpose of this study was to evaluate the LV function in patients with MS and to assess the relationship with the aortic distensibility, as possible underlying mechanism. Methods: We studied 53 patients with MS (27.0 ± 11 years, 29 men) without valvular or hypertensive heart disease and a control group of 26 healthy subjects (29 ± 9 years, 17 men). All underwent echocardiography and cardiac magnetic resonance (CMR) and the following indexes were analyzed: a) Echo: mitral flow velocities E/A ratio and deceleration of mitral E; E’ velocity obtained from the medial and lateral mitral ring; E/E’ ratio b) CMR: LV volumes indexed to BSA and ejection fraction (EF); global longitudinal strain (GLS, Circle cvI42); maximal size and distensibility of proximal ascending aorta. Distensibility was calculated from maximal (systolic) and minimum (diastolic) area of maximal proximal ascending aorta (cross-sectional images from SSFP sequence) using the formula=(maximum area-minimum area)/[ minimum area x (systolic BP-diastolic BP)]. Results: 17 from 53 patients with MS had increased LV end-diastolic volume, 14 decreased EF (<50%) and 22 decreased GLS. Compared with the control group, patients with MS showed increased LV end-diastolic volume (85.0 ± 5.2vs 80.1 ± 5.3ml/m2, p = 0.04), lower GLS (17.1 ± 1.9 vs 18.9 ± 2.2, p = 0.01) lower LVEF (53.0 ± 7.1% vs 56.0 ± 5.4%, p = 0.03) and higher E/E’ value (9.2 ± 1.3 vs. 6.2 ± 0.8, p = 0.01) as well as larger dimensions of proximal aorta (39 ± 2.2cm vs 32 ± 0.8,p = 0.010) and lower aortic distensibility (3.4 ± 1.9 vs. 4.4 ± 1.7 dynes cm-1, p = 0.03). In the group of patients, a correlation was found between the aortic distensibility and the LVEF (r = 0.47, p = 0.045) and GLS (r = 0.65, p = 0.02), but not with the other variables. Aortic distensibility was an independent predictor of LV dysfunction using a cutoff of 50% for LVEF and 19% for GLS. Conclusion: In our population of patients with MS, we found changes in the LV function, which were related with aortic distensibility, possibly sharing a common pathway. The prognostic significance of these findings is under evaluation.info:eu-repo/semantics/publishedVersio

The impact of exchanging the light and heavy chains on the structures of bovine ultralong antibodies

The third complementary‐determining regions of the heavy‐chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These `ultralong' CDR3Hs form β‐ribbon stalks that protrude from the surface of the antibody with a disulfide cross‐linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B‐cell sequencing, has been determined to 1.6 Å resolution. By swapping the D08 native light chain with that of an unrelated antigen‐unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing

The effect of videokeratoscope faceplate design on radius of curvature maps

A computer model using finite ray tracing methods was developed to simulate a videokeratoscope analysing an average cornea. Different faceplate designs were tested using five points in the faceplate subtending angles between 15 and 75 in 15 intervals at the corneal vertex. Image quality was assessed by adding the geometrical blurs of the 5 image points. Differences (error) between accurate sagittal radius of curvature and sagittal radius of curvature calculated by the van Saarloos algorithm were calculated for selected surfaces at the same corneal points. The calculations were repeated for the tangential radius of curvature. Differences equal or bigger than 0.02 mm were regarded as clinically significant. The surface that provided the sharpest image for an average cornea was a cylinder with the base 120 mm away from the corneal vertex and a diameter of 26 mm. Changing the faceplate design results in clinically significant differences for an average cornea

Essential Physiological Differences Characterize Short- and Long-Lived Strains of Drosophila melanogaster

Aging is a multifactorial process which affects all animals. Aging as a result of damage accumulation is the most accepted explanation but the proximal causes remain to be elucidated. There is also evidence indicating that aging has an important genetic component. Animal species age at different rates and specific signaling pathways, such as insulin/insulin-like growth factor, can regulate life span of individuals within a species by reprogramming cells in response to environmental changes. Here, we use an unbiased approach to identify novel factors that regulate life span in Drosophila melanogaster. We compare the transcriptome and metabolome of two wild-type strains used widely in aging research: short-lived Dahomey and long-lived Oregon R flies. We found that Dahomey flies carry several traits associated with short-lived individuals and species such as increased lipoxidative stress, decreased mitochondrial gene expression, and increased Target of Rapamycin signaling. Dahomey flies also have upregulated octopamine signaling known to stimulate foraging behavior. Accordingly, we present evidence that increased foraging behavior, under laboratory conditions where nutrients are in excess increases damage generation and accelerates aging. In summary, we have identified several new pathways, which influence longevity highlighting the contribution and importance of the genetic component of aging.This work was supported by the European Research Council (260632 - ComplexI&Aging to A.S.); the Academy of Finland (252048 to A.S); the Biotechnology and Biological Sciences Research Council ( BB/M023311/1 to A.S.); the Centre for International Mobility (CIMO) (TM-12- 8391 and TM-13-8919 to N.G.); the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (PI14/00328 to R.P. and PI17/01286 to P.N.); the Autonomous Government of Catalonia (2017SGR696 and SLT002/16/00250 to R.P.); the Ministry of Education and Science of Ukraine (grant number 0117U006426 to O.L.); FEDER funds from the European Union (“A way to build Europe” to R.P.); and the Doctoral Programme in Medicine and Life Sciences of University of Tampere (to T.R). R.S is a Sir Henry Wellcome Postdoctoral Fellow funded by Wellcome (204715/Z/16/Z

Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon

Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. We aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions. The anti-inflammatory efficacy of UDCA, a nonmetabolizable analog, 6 alpha-methyl-UDCA (6-MUDCA), and its primary colonic metabolite lithocholic acid (LCA) was assessed in the murine dextran sodium sulfate (DSS) model of mucosal injury. The effects of bile acids on cytokine (TNF-alpha, IL-6, Il-1 beta, and IFN-alpha) release from cultured colonic epithelial cells and mouse colonic tissue in vivo were investigated. Luminal bile acids were measured by gas chromatography-mass spectrometry. UDCA attenuated release of proinflammatory cytokines from colonic epithelial cells in vitro and was protective against the development of colonic inflammation in vivo. In contrast, although 6-MUDCA mimicked the effects of UDCA on epithelial cytokine release in vitro, it was ineffective in preventing inflammation in the DSS model. In UDCA-treated mice, LCA became the most common colonic bile acid. Finally, LCA treatment more potently inhibited epithelial cytokine release and protected against DSS-induced mucosal inflammation than did UDCA. These studies identify a new role for the primary metabolite of UDCA, LCA, in preventing colonic inflammation and suggest that microbial metabolism of UDCA is necessary for the full expression of its protective actions.NEW & NOTEWORTHY On the basis of its cytoprotective and anti-inflammatory actions, the secondary bile acid ursodeoxycholic acid (UDCA) has well-established uses in both traditional and Western medicine. We identify a new role for the primary metabolite of UDCA, lithocholic acid, as a potent inhibitor of intestinal inflammatory responses, and we present data to suggest that microbial metab-olism of UDCA is necessary for the full expression of its protective effects against colonic inflammation