Exercise-induced anaphylaxis: an update

Exercise-induced anaphylaxis (EIAn) is a rare and potentially fatal syndrome associated with exercise. It is the most serious and potentially life-threatening hypersensitivity phenomenon for athletes of all sports. Food-dependent EIAn (FDEIAn) shares the same symptoms, but ingestion of foods 2–3 h prior to exercise is crucial for its presentation. Attacks may seldom occur also if food ingestion is made 2–3 hours after exercise. Concomitant use of drugs, particularly aspirin and non-steroidal anti-inflammatory drugs, can worsen the clinical presentation. Clinical manifestations cover a wide range of symptoms, from pruritus to dyspnoea to vascular collapse. Differential diagnoses must be investigated when symptoms are unusual. Several pathogenetic theories have been formulated but the rarity of EIAn has not facilitated the efforts of scientists to find pathophysiological and immunological mechanisms that may account for these conditions. Diagnosis is mainly clinical and can be difficult. Validated protocols including skin prick testing together with food–exercise challenges, laboratory investigations looking for specific immunoglobulin E or through allergy molecular diagnostics are often required. Preventative measures are of fundamental importance, in particular regarding education of patients, family/ carers, trainers and teammates. Use of adrenaline autoinjectors is also fundamental and their correct use must be taught to patients, doctors and nurses. Pharmacological preventative measures are not supported by sufficiently powered studies. Further research will be needed to investigate deeper the complexities of EIAn

Investigation of Fretting Wear of Cladding Materials in Liquid Lead

One promising concept for future nuclear reactors uses liquid metals like Pb as reactor coolant. In this work, fretting of fuel clad materials is investigated in Pb environment at relevant operating conditions. A novel test apparatus is presented that allows fretting tests in liquid lead with high accuracy and reproducibility also during long term tests. Tolerable operating conditions concerning fretting wear by evaluating the specific wear coefficient and the concept of fretting maps are given

The Communicative Modes Analysis System in Psychotherapy From Mixed Methods Framework: Introducing a New Observation System for Classifying Verbal and Non-verbal Communication

Communication represents the core of psychotherapy. The dynamic interaction between verbal and non-verbal components during patient-therapist exchanges, indeed, promotes the co-construction of meanings bringing about change within a process of reciprocal influence of participants. Our paper aims to illustrate the building of a new observational instrument of the therapeutic discourse, the Communicative Modes Analysis System in Psychotherapy (CMASP), and its reliability study from Mixed Methods framework. The CMASP is a single classification system analyzing the communication features within therapeutic exchanges. Born to overcome the limits of traditional psychotherapy research which considers verbal and non-verbal dimensions of communication as in polar opposition, the CMASP building was based on the performative function derived from the Speech Act Theory. We used this function as a comprehensive theorization to interpret the communication components in psychotherapy as an integrated and interacting system. In fact, the instrument detects and classifies, at the overall and dimension level, the verbal and extra-linguistic components of psychotherapeutic communication implemented by the therapist and patients in the form of communicative modes. From the observational methodology framework, it was built an instrument able to record and analyze verbal, vocal and interruption behaviors by combining elements of qualitative and quantitative research approaches. The sample consisted of 30 psychotherapy audio recordings and verbatim transcripts of psychotherapy sessions (for a total of 8327 speaking turns). Four main dimensions were elaborated (Verbal Mode-Structural Form, Verbal Mode-Communicative Intent, Vocal Mode, and Interruption Mode) according to the agency role of communication components. The instrument is a field format combined with category systems. For each dimension, we built a category system that is exhaustive and mutually exclusive. From all dimensions, we have a total of 33 categories. Intra-and inter-judge reliability among four independent judges was computed on a total of 503 speaking turns coded through Cohen’s κ and Krippendorff’s canonical agreement coefficients (Cc), respectively. The CMASP showed high intra-and inter-judge agreement at the global, dimensional, and categorical level providing researchers and professionals with a single and flexible classification system, able to give multiple and concurrent information about the psychotherapy process

The Action of Verbal and Non-verbal Communication in the Therapeutic Alliance Construction: A Mixed Methods Approach to Assess the Initial Interactions With Depressed Patients

In psychodynamic psychotherapy, verbal (structures and intents) and non-verbal (voice and interruptions) dimensions of communication intertwine conveying information and determining the mutual regulation between therapist and patient through conversational sequences. The communication components interplay is the foundation for building the therapeutic alliance, a relational dimension that predicts a psychotherapy outcome and change, influenced by patient-therapist exchanges from the initial stages of their encounter. Depressed patients present specific verbal and non-verbal communication and show difficulties in developing and maintaining the therapeutic alliance. Based on the reviewed literature, the main aim of this study was to analyze how the action of specific communicative modes, implemented by the therapist and depressed patients, affect the reciprocal construction of the early therapeutic alliance by each participant during the mutual regulation processes. We employed a mixed methods approach based on a systematic observation of communication and alliance ruptures and repairs within the audio recordings and verbatim transcripts of 20 psychotherapy sessions (6,232 speaking turns) with seven depressed patients. The observational design was nomothetic, follow-up, and multidimensional. The choice of methodology is justified because we developed a comprehensive procedure that integrates an ad hoc indirect observation system (the Communicative Modes Analysis System in Psychotherapy), analyzing verbal and non-verbal communication, and an observational tool with deductive categories (the Collaborative Interactions Scale-Revised), assessing the therapeutic alliance construction. Once we confirmed the intra-and inter-observer reliability for the ad hoc system and the inter-rater reliability for the tool with deductive (or theoretical) categories, we performed descriptive statistics (to describe quantitatively communicative modes and alliance ruptures and repairs), lag sequential analysis (to detect stable patterns in communication-alliance interactions), and polar coordinate analysis (to identify significant relationships between communicative modes and alliance ruptures and repairs). Results confirm that the therapist's verbal (asking and exploring) and non-verbal (elaborating and cooperatively interrupting) modes and the depressed patients' verbal (asserting and exploring) and non-verbal (expressing emotions and cooperatively interrupting) modes determine stable patterns and significant associations with collaborative behaviors connected to the reciprocal construction of alliance by each participant. All this may provide professionals with useful information to increase the psychotherapy effectiveness with depressed patients

prox1b Activity Is Essential in Zebrafish Lymphangiogenesis

BACKGROUND: The lymphatic vascular system, draining interstitial fluids from most tissues and organs, exerts crucial functions in several physiological and pathological processes. Lymphatic system development depends on Prox1, the first marker to be expressed in the endothelial cells of the cardinal vein from where lymph vessels originate. Prox1 ortholog in the optically clear, easily manipulated zebrafish model has been previously isolated and its contribution to lymphangiogenesis has been clarified. Because of a round of genome duplication occurred at the base of teleosts radiation, several zebrafish genes have been retained in duplicate through evolution. We investigated for the presence of additional prox1 genes and determined their role in zebrafish lymphangiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: We isolated a second ortholog, named prox1b, and analyzed its expression during development by whole mount in situ hybridization (WISH). We detected strong prox1b expression in the endothelium of the posterior cardinal vein (PCV) from where lymphatic precursors originate. To analyze prox1b involvement in lymphangiogenesis we utilized the fli1:GFP transgenics and followed the formation of the toracic duct (TD), the primary lymph vessel in fish, after prox1b knockdown. Our findings clearly demonstrated that the absence of prox1b activity severely hampers the formation of the TD. CONCLUSIONS/SIGNIFICANCE: This work provides substantial progress toward the understanding of zebrafish lymphangiogenesis. In light of the features shared by the lymphatic systems of zebrafish and higher vertebrates, the establishment of such lymphatic model will provide a powerful tool to study, for instance, disorders of body fluid homeostasis, inflammation and cancer metastasis, and may ultimately contribute to novel therapies

Multimodal, open-source big data analysis in asthma: A novel approach to inform public health programming

Asthma is a chronic respiratory disease affecting over 358 million people worldwide; for this reason analysing big data on asthma from different countries could give a more detailed picture of current disease burden. We aim to investigate the correlations between asthma and key socio-demographic parameters from different world databases. We found a direct correlation with the gross domestic product (GDP) per capita and its nominal counterpart, with wealthiest countries seen to have the highest prevalence of asthma, as also confirmed by a similar correlation with the human development index (HDI). A positive correlation was also seen between asthma prevalence and a number of socio-cultural data being representative of a good life quality index and prevalent in more developed and wealthier countries. Concerning medical data, an inverse relationship was seen between asthma prevalence and helminthiasis. Those data indicate a higher prevalence for asthma in more developed countries, where socio-economic status is higher and also the access to medical care is more ubiquitous. The approach used in our study highlighted the role of medical literacy and access to healthcare facilities in the correct diagnosis of asthma and vice versa. Our data appear to be suitable in terms of a health programming approach because of the high burden of disease worldwide

COVID-19: Considerations about immune suppression and biologicals at the time of SARS-CoV-2 pandemic

The extent of the profound immunological and nonimmunological responses linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently being investigated worldwide due to the large burden associated with death due to SARS-CoV-2 and the short-term consequences of coronavirus disease 2019 (COVID-19). It has been hypothesized that patients on immunosuppressive treatments, including biologics, may have an augmented risk of being infected by SARS-CoV-2; however, there are currently no definitive data about biological drugs and COVID-19 in immune-mediated inflammatory diseases. Current epidemiological models developed to understand how long the COVID-19 epidemic may last are not conclusive and range from sustained epidemics to complete elimination. Nevertheless, even in the best-case scenario of apparent elimination, there is concordance about a possible contagion resurgence as late as 2024. Therefore, knowledge of the impact of SARS-CoV-2 on immune-mediated diseases and among patients treated with biologicals, together with the results of novel and promising COVID-19 treatment strategies targeting the virus and the host immune response (or both), will help us to best manage our patients during this pandemic over the next few years

Clinical pitfalls of leishmaniasis and Whipple’s disease hidden behind systemic lupus erythematosus: A case series

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that can affect major organs possibly leading to life-threatening complications and appears with heterogeneous clinical picture. SLE could present with broad spectrum of clinical and laboratory features that can resemble those of other diseases, such as hemopoietic malignancies, infections, or immune-mediated disorders. Its complexity and protean features overlap with many other diseases, hindering the differential diagnosis. Rarely, true overlap with other diseases may occur. Herein, we report a case series of two patients affected by infectious diseases, namely visceral leishmaniasis and Whipple’s disease (WD), intertwined with clinical or serological features of SLE. In both cases, several confounding factors have led to a delay in the diagnosis. Moreover, we first describe the persistent elevation of autoantibodies and a monoclonal gammopathy in a patient with WD. Awareness of unusual presentations of infections or other rare disorders, which may be encountered in clinical practice when taking care of SLE patients, is essential for timely diagnosis and treatment of potentially lethal diseases

development of a new reference standard for microarray experiments

Often microarray studies require a reference to indirectly compare the samples under observation. References based on pooled RNA from different cell lines have already been described (here referred to as RNA-R), but they usually do not exhaustively represent the set of genes printed on a chip, thus requiring many adjustments during the analyses. A reference could also be generated in vitro transcribing the collection of cDNA clones printed on the microarray in use (here referred to as T3-R). Here we describe an alternative and simpler PCR-based methodology to construct a similar reference (Chip-R), and we extensively test and compare it to both RNA-R and T3-R. The use of both Chip-R and T3-R dramatically increases the number of signals on the slides and gives more reproducible results than RNA-R. Each reference preparation is also evaluated in a simple microarray experiment comparing two different RNA populations. Our results show that the introduction of a reference always interferes with the analysis. Indeed, the direct comparison is able to identify more up- or down-regulated genes than any reference-mediated analysis. However, if a reference has to be used, Chip-R and T3-R are able to guarantee more reliable results than RNA-R

A Strategy analysis for genetic association studies with known inbreeding

Background: Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results: We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the betathalassemia, which is a well known Mendelian disease, and also to the common asthma where we have identified candidate genes that underlie to the susceptibility of the asthma. Some of such candidate genes have been also found related to common asthma in the current literature. Conclusions: The data analysis approach, based on selecting the most related cases and controls along with the Random Forest model, is a powerful tool for detecting genetic variants associated to a disease in isolated populations. Moreover, this method provides also a prediction model that has accuracy in estimating the unknown disease status and that can be generally used to build kit tests for a wide class of Mendelian diseases