Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria.

The original designation of "Arrhythmogenic right ventricular (dysplasia/) cardiomyopathy"(ARVC) was used by the scientists who first discovered the disease, in the pre-genetic and pre-cardiac magnetic resonance era, to describe a new heart muscle disease predominantly affecting the right ventricle, whose cardinal clinical manifestation was the occurrence of malignant ventricular arrhythmias. Subsequently, autopsy investigations, genotype-phenotype correlations studies and the increasing use of contrast-enhancement cardiac magnetic resonance showed that the fibro-fatty replacement of the myocardium represents the distinctive phenotypic feature of the disease that affects the myocardium of both ventricles, with left ventricular involvement which may parallel or exceed the severity of right ventricular involvement. This has led to the new designation of "Arrhythmogenic Cardiomyopathy" (ACM), that represents the evolution of the original term of ARVC. The present International Expert Consensus document proposes an upgrade of the criteria for diagnosis of the entire spectrum of the phenotypic variants of ACM. The proposed "Padua criteria" derive from the diagnostic approach to ACM, which has been developed over 30 years by the multidisciplinary team of basic researchers and clinical cardiologists of the Medical School of the University of Padua. The Padua criteria are a working framework to improve the diagnosis of ACM by introducing new diagnostic criteria regarding tissue characterization findings by contrast-enhanced cardiac magnetic resonance, depolarization/repolarization ECG abnormalities and ventricular arrhythmia features for diagnosis of the left ventricular phenotype. The proposed diagnostic criteria need to be further validated by future clinical studies in large cohorts of patients

Nitration of the Egg-Allergen Ovalbumin Enhances Protein Allergenicity but Reduces the Risk for Oral Sensitization in a Murine Model of Food Allergy

Nitration of proteins on tyrosine residues, which can occur due to polluted air under "summer smog" conditions, has been shown to increase the allergic potential of allergens. Since nitration of tyrosine residues is also observed during inflammatory responses, this modification could directly influence protein immunogenicity and might therefore contribute to food allergy induction. In the current study we have analyzed the impact of protein nitration on sensitization via the oral route.BALB/c mice were immunized intragastrically by feeding untreated ovalbumin (OVA), sham-nitrated ovalbumin (snOVA) or nitrated ovalbumin (nOVA) with or without concomitant acid-suppression. To analyze the impact of the sensitization route, the allergens were also injected intraperitoneally. Animals being fed OVA or snOVA under acid-suppressive medication developed significantly elevated levels of IgE, and increased titers of specific IgG1 and IgG2a antibodies. Interestingly, oral immunizations of nOVA under anti-acid treatment did not result in IgG and IgE formation. In contrast, intraperitoneal immunization induced high levels of OVA specific IgE, which were significantly increased in the group that received nOVA by injection. Furthermore, nOVA triggered significantly enhanced mediator release from RBL cells passively sensitized with sera from allergic mice. Gastric digestion experiments demonstrated protein nitration to interfere with protein stability as nOVA was easily degraded, whereas OVA and snOVA remained stable up to 120 min. Additionally, HPLC-chip-MS/MS analysis showed that one tyrosine residue (Y(107)) being very efficiently nitrated is part of an ovalbumin epitope recognized exclusively after oral sensitization.These data indicated that despite the enhanced triggering capacity in existing allergy, nitration of OVA may be associated with a reduced de novo sensitizing capability via the oral route due to enhanced protein digestibility and/or changes in antibody epitopes

Characterization of the Dispersal of Non-Domiciliated Triatoma dimidiata through the Selection of Spatially Explicit Models

Chagas disease is one of the most important neglected diseases in Latin America. Although insecticides have been successfully sprayed to control domiciliated vector populations, this strategy has proven to be ineffective in areas where non-domiciliated vectors immigrating from peridomestic or sylvatic ecotopes can (re-)infest houses. The development of strategies for the control of non-domiciliated vectors has thus been identified by the World Health Organization as a major challenge. Such development primarily requires a description of the spatio-temporal dynamics of infestation by these vectors, and a good understanding of their dispersal. We combined for the first time extensive spatio-temporal data sets describing house infestation dynamics by Triatoma dimidiata inside one village, and spatially explicit population dynamics models. The models fitted and predicted remarkably the observed infestation dynamics. They thus provided both key insights into the dispersal of T. dimidiata in this area, and a suitable mathematical background to evaluate the efficacy of various control strategies. Interestingly, the observed and modelled patterns of infestation suggest that interventions could focus on the periphery of the village, where there is the highest risk of transmission. Such spatial optimization may allow for reducing the cost of control, compensating for repeated interventions necessary for non-domiciliated vectors

Hystricognathy vs Sciurognathy in the Rodent Jaw: A New Morphometric Assessment of Hystricognathy Applied to the Living Fossil Laonastes (Diatomyidae)

While exceptional for an intense diversification of lineages, the evolutionary history of the order Rodentia comprises only a limited number of morphological morphotypes for the mandible. This situation could partly explain the intense debates about the taxonomic position of the latest described member of this clade, the Laotian rock rat Laonastes aenigmamus (Diatomyidae). This discovery has re-launched the debate on the definition of the Hystricognathi suborder identified using the angle of the jaw relative to the plane of the incisors. Our study aims to end this ambiguity. For clarity, it became necessary to revisit the entire morphological diversity of the mandible in extant and extinct rodents. However, current and past rodent diversity brings out the limitations of the qualitative descriptive approach and highlights the need for a quantitative approach. Here, we present the first descriptive comparison of the masticatory apparatus within the Ctenohystrica clade, in combining classic comparative anatomy with morphometrical methods. First, we quantified the shape of the mandible in rodents using 3D landmarks. Then, the analysis of osteological features was compared to myological features in order to understand the biomechanical origin of this morphological diversity. Among the morphological variation observed, the mandible of Laonastes aenigmamus displays an intermediate association of features that could be considered neither as sciurognathous nor as hystricognathous

Adaptive Developmental Delay in Chagas Disease Vectors: An Evolutionary Ecology Approach

The developmental time of vector insects is important to their population dynamics, evolutionary biology, epidemiology of the diseases they transmit, and to their responses to global climatic change. In various triatomine species vectors of Chagas disease (Triatominae, Reduviidae), a delay in the molt of a small proportion of individuals has been observed, and from an evolutionary ecology approach, we propose the hypothesis that the developmental delay is an adaptation to environmental stochasticity through a spreading of risk (bet-hedging) diapause strategy. We confirmed, by means of a survey among specialists, the existence of the developmental delay in triatomines. Statistical descriptions of the developmental time of 11 species of triatomines showed some degree of bi-modality in nine of them. We predicted by means of an optimization model which genotype, coding for a given frequency of developmental diapause, is expected to evolve. We identified a series of parameters that can be measured in the field and in the laboratory to test the hypothesis of an optimal diapause frequency. We also discuss the importance of these findings for triatomines in terms of global climatic change and epidemiological consequences such as their resistance to insecticides

Sex-Differences in the Pattern of Comorbidities, Functional Independence, and Mortality in Elderly Inpatients: Evidence from the RePoSI Register

Background: The RePoSi study has provided data on comorbidities, polypharmacy, and sex dimorphism in hospitalised elderly patients. Methods: We retrospectively analysed data collected from the 2010, 2012, 2014, and 2016 data sets of the RePoSi register. The aim of this study was to explore the sex-differences and to validate the multivariate model in the entire dataset with an expanded follow-up at 1 year. Results: Among 4714 patients, 51% were women and 49% were men. The disease distribution showed that diabetes, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy were more frequent in men but that hypertension, anaemia, osteoarthritis, depression, and diverticulitis disease were more common in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment, mood disorders, and disability in daily life measured by the Barthel Index (BI) were worse in women. In the multivariate analysis, BI, CIRS, and malignancy significantly increased the risk of death in men at the 1-year follow-up, while age was independently associated with mortality in women. Conclusions: Our study highlighted the relevance and the validity of our previous predictive model in the identification of sex dimorphism in hospitalised elderly patients underscoring the need of sex-personalised health-care

Precision measurement of CP\it{CP} violation in the penguin-mediated decay Bs0→ϕϕB_s^{0}\rightarrow\phi\phi

A flavor-tagged time-dependent angular analysis of the decay $B_s^{0}\rightarrow\phi\phi$ is performed using $pp$ collision data collected by the LHCb experiment at % at $\sqrt{s}=13$ TeV, the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The $\it{CP}$-violating phase and direct $\it{CP}$-violation parameter are measured to be $\phi_{s\bar{s}s} = -0.042 \pm 0.075 \pm 0.009$ rad and $|\lambda|=1.004\pm 0.030 \pm 0.009$, respectively, assuming the same values for all polarization states of the $\phi\phi$ system. In these results, the first uncertainties are statistical and the second systematic. These parameters are also determined separately for each polarization state, showing no evidence for polarization dependence. The results are combined with previous LHCb measurements using $pp$ collisions at center-of-mass energies of 7 and 8 TeV, yielding $\phi_{s\bar{s}s} = -0.074 \pm 0.069$ rad and $|lambda|=1.009 \pm 0.030$. This is the most precise study of time-dependent $\it{CP}$ violation in a penguin-dominated $B$ meson decay. The results are consistent with $\it{CP}$ symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb public pages

Measurement of the Λb0→Λ(1520)μ+μ−\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-} differential branching fraction

The branching fraction of the rare decay $\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-}$ is measured for the first time, in the squared dimuon mass intervals, $q^2$, excluding the $J/\psi$ and $\psi(2S)$ regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\ \mathrm{fb}^{-1}$. The result in the highest$q^{2}$interval,$q^{2} >15.0\ \mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model dependence, agrees with the predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-050.html (LHCb public pages