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Research shows that reduced exposure to natural contexts is associated with an increase in psychophysical disorders. Recent evidence suggests that even a brief experience in natural scenarios can positively affect people's health and well-being. However, natural contexts are not always easily accessible. This study investigates the effects of natural and indoor virtual environments (VREs) on psychophysiological and cognitive responses. Following a within-subject design, 34 healthy participants were exposed to two VREs (i.e., a forest and a living room) in a counterbalanced order through a head-mounted display (Oculus Rift). Participants were asked to explore the scenarios and execute a modified version of the Paced Auditory Serial Addition Test. Physiological parameters (heart rate, skin conductance level [SCL], and respiration rate) were recorded during the whole session. After the exposure to VREs, participants filled a set of visual analog scales to rate their subjective experience of presence, relaxation, and stress. Participants reported a higher perceived sense of relaxation in the virtual forest. Moreover, their SCLs were significantly higher in this environment, showing that the forest elicited higher physiological arousal than the living room. Furthermore, their SCLs were significantly higher during the attentional task in the virtual living room. The results suggest that a natural virtual environment can make people feel more relaxed and physiologically engaged than an indoor scenario. The latter instead can be linked to a performing venue, as reported for real contexts. However, these changes were not related to modulations of attentional performance.

Computer graphics is-in many cases-about visualizing what you cannot see. However, virtual reality (VR), from its beginnings, aimed at stimulating all human senses: not just the visual channel. Moreover, this set of multisensory stimuli allows users to feel present and able to interact with the virtual environment. In this way, VR aims to deliver experiences that are comparable to real-life ones in their level of detail and stimulation, intensity, and impact. Hence, VR is not only a means to see, but also to feel differently. With the spreading of VR technologies, there is a growing interest in using VR to evoke emotions, including positive and negative ones. This article discusses the current possibilities and the authors' experience collected in the field in trying to elicit emotions through VR. It explores how different design aspects and features can be used, describing their contributions and benefits in the development of affective VR experiences. This work aims at raising awareness of the necessity to consider and explore the full design space that VR technology provides in comparison to traditional media. Additionally, it provides possible tracks of VR affective applications, illustrating how they could impact our emotions and improve our life, and providing guidelines for their development.

Long coronavirus disease 19 (COVID-19) is the designation given to a novel syndrome that develops within a few months after infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and that is presenting with increasing incidence because of the numerous cases of infection. Long COVID-19 is characterized by a sequela of clinical symptoms that concern different organs and tissues, from nervous, respiratory, gastrointestinal, and renal systems to skeletal muscle and cardiovascular apparatus. The main common molecular cause for all long COVID-19 facets appears to be related to immune dysregulations, the persistence of inflammatory status, epigenetic modifications, and alterations of neurotrophin release. The prevention and management of long COVID-19 are still inappropriate because many aspects need further clarification. Exercise is known to exert a deep action on molecular dysfunctions elicited by long COVID-19 depending on training intensity, duration, and continuity. Evidence suggests that it could improve the quality of life of long COVID-19 patients. This review explores the main clinical features and the known molecular mechanisms underlying long COVID-19 in the perspective of considering exercise as a co-medication in long COVID-19 management.

This group randomized control trial examined the dose-response effect of varied combinations of linear and nonlinear pedagogy (enriched physical education with specific program led by specialist vs. conventional physical education led by generalist) for improving first-grade children’s motor creativity, executive functions, self-efficacy, and learning enjoyment. We led three physical education classes per group through 12 weeks of combined instruction, based on linear and nonlinear pedagogy: mostly linear (ML; 80% linear, 20% nonlinear; n = 62); mostly nonlinear (MNL; 20% linear, 80% nonlinear; n = 61); and control (C; conventional teaching from generalists; n = 60). MNL improved in (a) motor creativity ability (DMA; 48.7%, 76.5%, and 47.6% for locomotor, stability, and manipulative tasks, respectively); (b) executive functions (working memory and inhibitory control) for RNG task (14.7%) and task errors (70.8%); (c) self-efficacy (5.9%); and (d) enjoyment (8.3%). In ML, DMA improved by 18.0% in locomotor and 60.9% in manipulative tasks. C improved of 10.5% in enjoyment, and RNG task worsened by 22.6%. MNL improvements in DMA tasks, executive functions, and self-efficacy were significantly better than those in C. ML was better than C in DMA task and in executive functions’ task errors. Overall, ML and MNL approaches were more effective than conventional generalist teaching (C), and the MNL combination of 80% nonlinear and 20% linear pedagogy was optimal. We recommend that educators favor the MNL approach.

Physical activity (PA) is a major health factor and studies suggest workplaces could promote PA by modifying office design, motivational strategies and technology. The present study aims to evaluate the efficiency of UP150, a multifactorial workplace intervention for the improvement and maintenance of the level of physical fitness (PF) and wellbeing. Forty-five employees were randomly divided into the experimental (EG) and control (CG) groups. The PF was assessed pre-post intervention using the cubo fitness test (CFT), the amount of PA was evaluated using the IPAQ questionnaire and accelerometers while the workload was assessed using the NASA-TLX questionnaire and psycho-physical health by using the SF-12 questionnaire. The EG worked in UP150 offices while the CG worked in their usual offices for 8 weeks. The EG and CG came back 4 weeks after the intervention for CFT retention. The EG improved CFT motor efficiency and the amount of moderate PA, while it reduced mental load. The EG retained reached motor efficiency levels 4 weeks after the intervention. No differences were found in IPAQ. The UP150 demonstrated to be a proactive environment and to be efficient in the promotion of PA, improving PF and mental health while decreasing mental load.

The passive drag (Dp) during swimming is affected by the swimmer&rsquo, s morphology, body density and body position. We evaluated the relative contribution of morphology, body composition, and body position adjustments in the prediction of a swimmer&rsquo, s Dp. This observational study examined a sample of 60 competitive swimmers (31 male and 29 female) with a mean (&plusmn, SD) age of 15.4 &plusmn, 3.1 years. The swimmer&rsquo, s Dp was measured using an electro-mechanical towing device and the body composition was assessed using a bioelectrical impedance analyser. Body lengths and circumferences were measured in both the standing position and the simulated streamlined position. Partial correlation analysis with age as a control variable showed that Dp was largely correlated (p &lt, 0.05) with body mass, biacromial- and bi-iliac-breadth, streamline chest circumference and breadth. Body mass, Body Mass Index, chest circumference and streamline chest circumference showed a significant and moderate to strong effect (&eta, 2 &gt, 0.55) on Dp. Body mass was the best predictor of Dp explaining 69% of the variability. These results indicate that swimmers with lower Dp values were: (i) slimmer, with lower fat and fat-free mass, (ii) thinner, with lower shoulder breadth, chest circumference, and streamline trunk diameters (iii), shorter, with lower streamline height. These findings can be used for talent identification in swimming, with particular reference to the gliding performance.

Teaching physical education requires competencies to conduct the classes and to assess the motor skills of practitioners. Specialists (physical education professionals) and generalists (primary school teachers) differently experienced motor tasks during their academic education. This study aimed to compare the teachers&rsquo, ability in assessing the children&rsquo, s forward and backward rolls from the analysis of the reliability of an evaluation grid of rolling abilities (Information Scale for Agility on the Soil, InfoSAS), which was investigated in a first study with teachers. A second study in young children explored the responsiveness of the InfoSAS to discriminate by skill level or by training effects. When administered by specialists, the InfoSAS resulted in being reliable (forward: p = 0.087 and p = 0.908, backward: p = 0.926 and p = 0.910, intra- and inter-rater reliability, respectively) and responsive in detecting differences due to expertise (gymnasts vs. primary school children, forward: p = 0.003, backward: p = 0.016) or improvements after specific training in rolling (pre- vs. post-children&rsquo, s training, forward: p = 0.005, backward: p = 0.001). The results support the conclusion that specialists exhibit higher competence than generalists, which allows proper application of the InfoSAS, possibly because of the practice of skills and reflective teaching styles in physical activity they experienced, along with their academic education in sport sciences.

Background Sudden unexpected postnatal collapse of presumably healthy neonates during early skin-to-skin contact is a rare, yet recognized occurrence, associated with a high risk of mortality and morbidity. A survey was conducted in 2012 in 30 delivery wards throughout Piedmont and the Aosta Valley to evaluate the environmental and logistical aspects that could be linked to SUPC. The survey was again conducted in 2016 in 28 delivery wards in Piedmont and the Aosta Valley in order to evaluate organizational improvements introduced after ministerial indications and recommendations by the Italian Society of Neonatology were published in 2014, in light of new findings regarding the phenomenon. Methods A questionnaire specifically asking about the organization of delivery wards, and surveillance or supervision during early skin-to-skin contact, was sent to all of the hospitals taking part in the survey in both 2012 and 2016. The collected data were elaborated anonymously and the statistical analysis was performed by using the two by two table. Results In 2012, 28 out of 30 delivery wards in Piedmont and Aosta, with a total of 31,074 newborns out of 35,435, were evaluated in all of the environmental and logistical aspects that might be cause for SUPC to occur. An identical survey was taken again in 2016; 26 out of 28 wards participated with a total of 27,484 newborns out of 30,339. In 2012, early skin-to-skin contact took place immediately in all the delivery rooms in 27 wards, and soon after in the post-partum room in one; in 11 out of 28 wards there was early skin-to-skin contact in the operating theater itself, following caesarean sections (11/26 in 2016). Routine newborn care was given after 3 h in 8 delivery wards (7/26 in 2016); after 2 h in 12 (7/26 in 2016); after 1 h in 2 (4/26 in 2016); after 30 min in 3 (2/26 in 2016); after 10 min in 1 (0/26 in 2016); after 1 or 2 min in 1 (0/26 in 2016) and at any time in one ward (6/26 in 2016). Conclusion Periodic surveys of delivery wards are useful for the assessment of all the aspects and risk factors that need to be changed in order to implement safe early skin-to-skin contact. Electronic supplementary material The online version of this article (10.1186/s13052-019-0688-9) contains supplementary material, which is available to authorized users.

International audience; The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.

The circadian rhythm plays a fundamental role in regulating biological functions, including sleep–wake preference, body temperature, hormonal secretion, food intake, and cognitive and physical performance. Alterations in circadian rhythm can lead to chronic disease and impaired sleep. The circadian rhythmicity in human beings is represented by a complex phenotype. Indeed, over a 24-h period, a person’s preferred time to be more active or to sleep can be expressed in the concept of morningness–eveningness. Three chronotypes are distinguished: Morning, Neither, and Evening-types. Interindividual differences in chronotypes need to be considered to reduce the negative effects of circadian disruptions on health. In the present review, we examine the bi-directional influences of the rest–activity circadian rhythm and sleep–wake cycle in chronic pathologies and disorders. We analyze the concept and the main characteristics of the three chronotypes.

BACKGROUND Respiratory muscle training has been shown to provide positive effects for both health and performance purposes. The aim of this study was to evaluate the effects of a six-week period of nasal breathing on pulmonary function and cardio-respiratory fitness in young basketball players. METHODS Thirty-four, male, basketball players were enrolled and assigned either to experimental group (EG) or to control group (CG). All participants were tested for Yo-Yo Intermittent Recovery level 1 (Yo-Yo IR1), Shuttle Sprint Test (SST), Forced Vitality Capacity (FVC), Forced Expiratory Volume in one second (FEV1) and Peak Expiratory Flow (PEF). EG group followed reduced breathing frequency training program focused on intermittent running exercises while performing nasal breathing. RESULTS The main findings were significant interactions in Yo-Yo IR1 test, FVC, FEV1 and PEF (p

Despite the great potential of Virtual Reality (VR) to arouse emotions, there are no VR affective databases available as it happens for pictures, videos, and sounds. In this paper, we describe the validation of ten affective interactive Virtual Environments (VEs) designed to be used in Virtual Reality. These environments are related to five emotions. The testing phase included using two different experimental setups to deliver the overall experience. The setup did not include any immersive VR technology, because of the ongoing COVID-19 pandemic, but the VEs were designed to run on stereoscopic visual displays. We collected measures related to the participants’ emotional experience based on six discrete emotional categories plus neutrality and we included an assessment of the sense of presence related to the different experiences. The results showed how the scenarios can be differentiated according to the emotion aroused. Finally, the comparison between the two experimental setups demonstrated high reliability of the experience and strong adaptability of the scenarios to different contexts of use.

Drag is the resistant force that opposes a swimmer displacing through water and significantly affects swimming performance. Drag experienced during active swimming is called active drag (D a ), and its direct determination is still controversial. By contrast, drag experienced while gliding in a stable streamlined body position is defined as passive drag (D p ), and its assessment is widely agreed upon. D p reduction preserves the high velocity gained with the push-off from the starting block or wall after starting and turning or improves the gliding phase of the breaststroke cycle. Hence, this paper reviewed studies on swimming that measured D p under different conditions of gliding. In the present research, accurate descriptions of the main methods used to directly or indirectly determine D p are provided and the main advantages, limitations and critical features of each method are discussed. Since D p differs in methods but not in reported values and is consistent regardless of the measuring method, the information provided in this paper might allow coaches and practitioners to identify the most suitable method for assessing and determining the drag of their swimmers.

The present study investigated the relationship between local fat percentage (SKfat) and muscle quality (MQ) estimated by a new hand-held electrical impedance myography (hEIM) device or derived fro...

Circadian rhythms influence daily behavior, psychological and physiological functions, as well as physical performance. Three chronotypes are distinguished according to the preferences people typically display for activity at certain times of day: Morning, Neither, and Evening types (M-, N- and E-types). The chronotype changes with age: eveningness tends to be stronger in youth and morningness in older age. The progressive shift toward eveningness during adolescence creates misalignment with morning society schedules and can lead to a deterioration in intellectual and physical performance. Soccer is one of the world's most popular sports practiced by adolescents and soccer workouts are usually held after school in the afternoon or evening. Performance in soccer is related to a host of factors, including physiological variables and motor skills that have a circadian variation. The aim of this study was to determine the effect of chronotype on motor skills specific to soccer, specifically whether agility, aerobic endurance, and explosive power differ among the three chronotypes in relation to the time of day. For this study 141 adolescent soccer players filled in the Morningness-Eveningness Questionnaire (MEQ) for the assessment of chronotype. A subsample of 75 subjects, subdivided in M-types (n= 25), E-types (n= 25), and N-types (n= 25), performed three tests (Sargent Jump Test - SJT, Illinois Agility Test - IAT, and 6-Minutes Run Test - 6MRT) at a morning and an evening training session (9:00 am and 6:00 pm). Mixed ANOVA was used to test the interactions between chronotypes, physical performance, and time. On all tests, better performance during the morning than the evening session was observed for the M-types (

In the past, the use of external fixation technique (FE) in children was limited, as the patient's compliance to the treatment was scarce due to an important visual impact for the little patient. With the evolution of the surgical approach and the technology of fixators, we have been able to considerably implement the treatment possibilities, thus allowing for an immediate load bearing of the operated limb and for the early mobilization of the joints. The FE technique does not represent an overcoming of classical synthesis techniques by internal fixation with elastic intramedullary nails, but it simply offers a valid treatment alternative to selected cases. In this work, we radiologically and clinically evaluated pediatric patients treated with FE for diaphyseal fractures of the lower limb and we compared them with patients treated with standard Titanium Endomedullary Nail (TEN) techniques. Our results confirmed that FE is a valid alternative treatment for these types of fractures.

Purpose:To assess the effects of acute combined L-carnosine and β-alanine (Carn-BA) supplementation on isometric and dynamic tasks.Methods:Twelve healthy participants performed knee-extensor maximal voluntary contractions (MVCs) and countermovement jumps (CMJs) before and after a fatiguing protocol (45-s continuous CMJs). Isometric and dynamic tests were performed 4 h after ingestion of Carn-BA (2 g of L-carnosine and 2 g of β-alanine) or placebo (PLA), in random order. After the fatiguing protocol, blood lactate concentration ([La−]), general and muscular rating of perceived exertion (RPE), and muscle pain (24 and 48 h after the end of the fatiguing protocol) were assessed.Results:During the fatiguing protocol, significant decreases in jump height and increases in contact time were found in both groups from the 15th second onward to the end of the fatiguing protocol. Average contact time and jump height were respectively lower (−7%; P = .018) and higher (+6%; P = .025) in Carn-BA than in PLA. After the fatiguing protocol, MVC decreased in both PLA and Carn-BA, but it was higher in Carn-BA than in PLA (+15%, P = 0.012), while CMJ did not change. Moreover, general RPE was lower and muscle pain at 24 h was higher in Carn-BA than in PLA, whereas muscle RPE and [La−] did not differ between conditions.Conclusions:Ingesting Carn-BA before exercise induced positive effects on MVC and CMJ after the fatiguing protocol and improved CMJ performance during the 45-s continuous jumping effort, even when acutely supplemented. Furthermore, Carn-BA reduced the general RPE and increased muscle pain 24 h after the fatiguing task.

Background This study investigated the differences in strength, technique and time performance in in-line skaters of three age categories during a 300-meter trial. Possible correlations among these variables were also assessed. Methods Thirty-six elite in-line skaters (Cadets, Juniors and Seniors, N.=12 each; 14±1, 16±1, and 24±6 years of age, respectively) performed a 300-m trial on an outdoor oval track. Total time (Ttot), 100-m fractions and duration of each skating technique (initial acceleration phase, straight push and cross-over) were recorded. A squat jump (SJ) was performed before and after the trial. Heart rate, blood lactate concentration ([La-]) and rate of perceived exertion (RPE) were collected before, during and at the end of the trial. Results Ttot was longer and SJ lower in Cadets compared to the other groups. Seniors employed the cross-over technique for a longer period than the straight push technique, compared to Juniors and Cadets. Ttot correlated negatively with SJ in Seniors. The number of significant correlations between skating techniques' duration and both Ttot and SJ increased with age category. No differences among groups were found for heart rate, [La-] and RPE. Conclusions With increasing age category, leg strength appeared to be the more related aspect to skating performance. To improve 300-m in-line skating performance, trainers should pay particular attention to the enhancement of leg strength and cross-over skating technique.

Introduction Liquid chromatography coupled to atmospheric pressure ionization tandem mass spectrometry (LC-ESI-MS/MS) is currently considered the reference method for quantitative determination of urinary free cortisol (UFC). One of the major drawbacks of this measurement is a particular form of matrix effect, conventionally known as ion suppression. Materials and methods We describe here the case of a 66-year-old-patient referred to the daily service of general medicine for intravenous antibiotic administration due to a generalized Staphylococcus aureus infection and for routine 24 hours UFC monitoring in the setting of glucocorticoid replacement therapy. Results The observation of 10-fold decrease of internal standard of cortisol signal led us to hypothesize the presence of an ion suppression effect due to a co-eluting endogenous compound. Screening analysis of tandem mass spectrometry (MS/MS) spectra of the interfering molecule, along with in vitro confirmation analyses, were suggestive of the presence of high concentration of piperacillin. The problem was then easily solved with minor modifications of the chromatographic technique. Conclusions According to our findings, antibiotic therapy with piperacillin/tazobactam should be regarded as an important interference in UFC assessment, which may potentially affect detection capability, precision and accuracy of this measurement. This case report emphasizes that accurate anamnesis and standardization of all phases of urine collection are essential aspects for preventing potential interference in laboratory testing.

This study assessed how accurately professional swimmers can interpret instructions to swim “slow,” “moderate,” and “fast.” 8 distance swimmers (6 males, 2 females; M age = 19 yr., SD = 3) and 8 sprint swimmers (7 males, 1 female; M age = 18yr., SD = 1) performed an all-out 50-m crawl stroke and three sets of 8 × 50-m crawl stroke trials interpreting the coach's instruction to swim at slow, moderate, and fast paces. No differences were detected between groups in absolute speed. Nevertheless, distance and sprint swimmers significantly differed in speed normalized to their own 50-m all-out speed (effect sizes = 6.72, 6.20, 1.35 for slow, moderate, and fast, respectively), stroke frequency (effect sizes = 0.81, 1.12, 1.54, respectively), and blood lactate concentration (effect sizes = 0.99, 2.56, 1.70, respectively).

High-level physical performance in rhythmic gymnastics is influenced by numerous skills and anthropometric factors. In order to understand if genetic predisposition could play a role to define the elite rhythmic gymnast phenotype, we analysed the frequency of common polymorphisms linked to genes correlated with body mass (ADRB2 and FTO), explosive strength (ACTN3 and ACE), and joint mobility (COL5A1), in 42 gymnasts involved in National and International events, and in 42 control girls. Our results demonstrated that high-level rhythmic gymnasts constituted a genetically selected population showing higher frequency of: (a) ADRB2 and FTO alleles linked to low body mass index and low fat mass; (b) COL5A1 CT genotype linked to high joint mobility and to the occurrence of genu recurvatum, but also to a higher incidence of injuries. ACTN3 and ACE polymorphisms did not appear to be connected with the phenotype of high-level rhythmic gymnast. Based on these data, it can be assumed that these polymorphisms could positively affect the phenotype and performance of gymnasts.

BACKGROUND: Cinacalcet hydrochloride is a calcimimetic agent indicated for the treatment of secondary hyperparathyroidism in dialysis-dependent patients with chronic kidney disease. In the context of a pharmacokinetic (PK)/pharmacodynamic study of cinacalcet in dialysis-dependent chronic kidney disease children with secondary hyperparathyroidism, we describe the development and validation of a new, rapid, simple, and economical liquid chromatography-tandem mass spectrometry (LC-MS/MS) micromethod for quantifying cinacalcet plasma concentrations. METHODS: Cinacalcet was analyzed in 50-μL plasma samples over a wide range of concentrations (0.1-100 ng/mL) by LC-MS/MS after protein precipitation and addition of deuterated cinacalcet as the internal standard. Cinacalcet was quantified using selective reaction monitoring of the specific transition m/z 358.1 > 155.1, with the 361.1 > 158.1 transition used for the internal standard. The suitability of the assay for clinical PK studies was evaluated using data from a pilot PK study in a pediatric patient. RESULTS: The overall turnaround time for the assay was 20 minutes. The lower limit of quantification of the method was 0.1 ng/mL. Intraassay imprecision and inaccuracy for quality control samples ranged from 2.8% to 9% and 100% to 102%, respectively. Interassay imprecision and inaccuracy ranged from 6.9% to 8.5% and 99% to 103%, respectively. The overall recovery ranged from 90% to 106%. No ion suppression due to matrix effects was found with different preanalytical conditions, such as hemolysis, lipemia, and hyperuricemia. CONCLUSIONS: This LC-MS/MS micromethod provides high specificity, precision, and accuracy for rapid quantification of cinacalcet plasma concentrations, and it is suitable for application in pediatric PK studies; it also has potential for use in the establishment of target ranges and ultimately routine therapeutic drug monitoring to optimize cinacalcet dosing.

Penconazole (PEN) is a fungicide used in agriculture that has been classified as hazardous to humans and the environment. The objective of this work was to identify PEN urinary metabolites in humans and propose a biomarker for PEN exposure. Five urine samples were collected from agricultural workers who worked with and were exposed to PEN. Samples were analyzed by liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry, with the source operating in the electrospray ionization mode. Metabolites previously identified in animal studies were searched as possible metabolites in humans. Candidate metabolites were first identified by multiple reaction monitoring following the protonated molecular ions that generated the protonated triazole moiety, which is expected to be present in all PEN metabolites; second, the isotopic patterns of the molecular ions were checked for consistency with the presence of two chlorine atoms; third, the full mass spectra were evaluated for consistency with the molecular structure. Seven different oxidized metabolites were found, both in the free and glucuronide conjugate forms. The major metabolite was the monohydroxyl-derivative PEN-OH (median molar fraction approximately 0.92 as a sum of free and glucuronide conjugated form). The product of further oxidation was the carboxyl-derivate PEN-COOH (median molar fraction approximately 0.03). After hydrolysis with β-glucuronidase, the free compounds were quantified in the presence of deuterated PEN as an internal standard; PEN-OH levels ranged from 230 to 460 μg/L, and PEN-COOH levels ranged from 5.2 to 16.7 μg/L. We propose a pathway for PEN metabolism in humans and suggest PEN-OH, after hydrolysis of glucuronide conjugates, as a biomarker for monitoring human exposure to PEN.

Polysensitization, that is, sensitization to more than one allergen family, is a common feature of patients with allergic rhinitis (AR) and significantly impairs their quality of life (QoL). Allergen-specific immunotherapy is the only causal treatment for AR. However, the polysensitization phenomenon may represent a crucial obstacle as far as it concerns the choice of the allergen extract to be used for immunotherapy.A series of real-life based multi-center studies, named POLISMAIL (Polysensitization Impact on Allergen Immunotherapy), have been designed with the aim of evaluating the behavior of allergists in managing polysensitized AR patients. The effect of immunotherapy treatment in these patients was also evaluated. A single allergen extract was used in two-thirds of patients, whereas a mix of two allergens was chosen in the remaining. The severity grade of AR and the QoL were significantly improved by immunotherapy. Both outcomes confirmed that immunotherapy with one or two allergen extracts achieves a significant improvement in polysensitized patients.In conclusion, POLISMAIL studies demonstrate that polysensitization should not represent a counter-indication for prescribing immunotherapy. The choice of limiting sublingual immunotherapy to one to two allergen extracts, preferably separated and at high dosages, is sufficient and effective in improving symptoms and QoL.

Polysensitization is a feature of allergic rhinitis (AR) that significantly impairs the quality of life (QoL) of AR patients. Allergen-specific immunotherapy is the only causal therapy for AR. However, the polysensitization phenomenon may represent a crucial obstacle as far as it concerns the choice of the allergen extract which should be used for immunotherapy. Therefore, a real-life based multicentre study, named POLISMAIL, has been designed which aims at evaluating the behaviour of some allergists managing polysensitized AR patients. The effect of two-year SLIT treatment in those patients was also evaluated. A single allergen extract was used for two-thirds of patients, whereas a mix of two allergens was chosen for the remaining patients. The severity grade of AR and the type of diagnosis were significantly improved by 2-year SLIT. In addition, SLIT significantly improved QoL. Both outcomes confirm that SLIT with one or two allergen extracts achieves a significant improvement in polysensitized patients. In conclusion, the POLISMAIL study demonstrates that polysensitization should not represent a counter-indication for prescribing immunotherapy. The choice to limit SLIT to 1–2 allergen extracts was sufficient and effective in improving symptoms and QoL.

Both F(2)-isoprostanes (8-iso-PGF(2alpha)), a well-known marker of oxidative stress, and thromboxanes A(2) (TXA(2)) are involved in atherosclerosis through LDL oxidation and platelet activation. Different aspects of the pathology can be described by 8-iso-PGF(2alpha) and TXA(2) so it is important to determine both their concentrations to monitor the disease progression and/or therapy effects. We developed a simple and sensitive method based on liquid chromatography-tandem mass spectrometry, using electrospray ionization in negative-ion mode, for the simultaneous measurement of the concentration of 8-iso-PGF(2alpha) and 11-dehydro thromboxane B(2) (11-DH-TXB(2)), a TXA(2) metabolite. This method was applied to analyze urine samples collected overnight from 15 atherosclerotic patients, with documented carotid artery sclerosis (CAS), and from 20 controls. The detection limit was 0.097pg/microL for 8-iso-PGF(2alpha) and 0.375pg/microL for 11-DH-TXB(2), with a linear range of 0.78-25pg/microL; the inter- and intraday imprecision was

Specific immunotherapy (IT) is an effective treatment for rhinitis and asthma caused by aeroallergens sensitization. Sublingual IT (SLIT) was introduced to solve the problem of systemic reactions to subcutaneous IT (SCIT) and developed to represent an actual treatment option. It is now generally accepted that allergen doses much higher than those administered by SCIT must be used to achieve clinical efficacy on allergic symptoms.To evaluate the characteristics of Staloral, an allergen extract produced by Stallergenes (Antony, France) in terms of practical administration, efficacy, safety and mechanism of action.Data were obtained from 20 double-blind, placebo-controlled studies using Staloral in patients sensitized to pollens and house-dust mites, and also from open studies concerning practical administration and the mechanism of action.Efficacy and safety of Staloral, as demonstrated by the revision of the studies, which used doses up to 1125 times those administered with SCIT, are very satisfactory and confer to this allergen extract optimal characteristics for treating patients with seasonal allergies due to pollens or with perennial symptoms induced by dust mites. The main mechanism of action is the interaction with dendritic cells of the oral mucosa and the subsequent tolerance induced in T cells.

Background. Available data about oxidative status in patients with end-stage renal disease (ESRD) or on dialysis are contradictory. The present cross-sectional study aimed to investigate the role of renal insufficiency and dialysis on lipid peroxidation. To separate the effects of uraemia from dialysis-induced stress, we enrolled 26 patients with renal insufficiency on conservative treatment (ESRD), 23 on peritoneal dialysis (PD), 30 on haemodialysis (HD) and 30 controls. Methods. Plasma malondialdehyde (MDA) levels, both total (tMDA) and free (fMDA), were measured as indexes of oxidative stress by gas chromatography-mass spectrometry. Bound MDA (bMDA) levels were calculated as the difference between tMDA and fMDA. Results. Total and bMDA concentrations were significantly higher in patients than in controls (ESRD > HD > PD). In PD and HD patients, fMDA levels were similar and significantly higher than in ESRD. Multivariate analysis, with tMDA, fMDA and bMDA as dependent variables, showed similar and significant tMDA and bMDA relations with residual renal function (t = -2.160, P = 0.035) and albumin (t = -2.049, P = 0.045). Erythropoietin dose affected only fMDA values (t = -2.178, P = 0.034). Conclusions. Free and bMDA concentrations identified different MDA patterns. Bound MDA, not excreted by kidneys, accounts alone for high tMDA concentrations in ESRD patients, while both fMDA and bMDA contribute to tMDA values in dialysis patients. These findings show that increased tMDA could be indicative not only of recent lipid peroxidation, and they also highlight the importance of evaluating free, bound and total MDA in patients with reduced renal function in order to assess their oxidative status.

Antiphospholipid antibodies (Abs) are associated with thrombosis and are a risk factor for recurrent pregnancy loss and obstetric complications in patients with the antiphospholipid syndrome. It is generally accepted that the major autoantigen for aPL Abs is beta (2) glycoprotein I, which mediates the binding of aPL Abs to target cells (i.e., endothelial cells, monocytes, platelets, trophoblasts, etc.) leading to thrombosis and fetal loss. This article addresses molecular events triggered by aPL Abs on endothelial cells, platelets, and monocytes and complement activation, as well as a review of the current knowledge with regard to the putative receptor(s) recognized by aPL Abs on target cells as well as novel mechanisms that involve fibrinolytic processes. A section is devoted to the description of thrombotic and inflammatory processes that lead to obstetric complications mediated by aPL Abs. Based on experimental evidence using in vitro and in vivo models, new targeted therapies for treatment and/or prevention of thrombosis and pregnancy loss in antiphospholipid syndrome are proposed.

The aim of this study was to observe the cardiovascular demands by monitoring the heart rate (HR) and the pacing strategy by evaluating the speed during a simulated cross-country skiing race. Eleven skiers (16.45 ± 1.67 yrs; 21.32 ± 2.03 kg m(-2); 72.35 ± 4.69 mL min(-1) kg(-1)) competed in a 10 km event divided into four laps. The HR profile was classified into four intensity zones. The skiers spent 66.84 ± 23.64% and 31.82 ± 23.77% of the total time above 90% and at 80-90% of the HRmax respectively, whereas the lower zones were negligible. During the event, a progressive increase in intensity was observed: HRmean raised by 2.42% in the last versus the first lap (p < 0.001). The skiers decreased their speed in the second (p = 0.017) and the third laps (p < 0.001) compared to with the first lap. In the fourth lap the skiers increased the speed slightly but without statistical difference. The speed maintained by the skiers resulted in the adoption of a reverse J-shaped pacing strategy.

Allergic rhinitis is characterized by troublesome symptoms that may be particularly severe. Most of rhinitics are dissatisfied with drug treatments. The dissatisfaction level depends on symptoms severity, but not on the type of causal allergen.

Tebuconazole (TEB) is a fungicide used in agriculture; the objective of this work was to identify and quantify TEB metabolites in human urine. Samples from seven vineyard workers exposed to TEB were submitted to liquid chromatography interfaced with a triple quadrupole mass spectrometer, equipped with an electron spray source, and a linear ion trap to gain a profile of candidate metabolites. Based on the presence of the ion m/z 70 in the MS/MS spectra, which corresponds to protonated triazole (a specific moiety of TEB), and the isotopic pattern of the molecular ions, typical of molecules with one chlorine atom, hydroxyl and carboxyl derivatives of TEB, that is, TEB-OH and TEB-COOH, were identified as major metabolites, both as free molecules and as glucuronide (Glc) conjugates. The mean molar fractions were 0.67, 0.13, 0.13, and 0.07 for TEB-O-Glc, TEB-OH, TEB-COO-Glc, and TEB-COOH. Urine samples were submitted to hydrolysis with β-glucuronidase, and the free compounds were quantified in the presence of deuterated TEB (TEB-d6) as the internal standard (IS), by multiple reaction monitoring (MRM) mode. The assay was linear in the ranges of 0.2-600 μg/L and 0.1-240 μg/L for TEB-OH and TEB-COOH, respectively; precision, accuracy, and the limit of quantification (LOQ) were

Background: Cystic fibrosis per se can sometimes lead to hyponatremia, hypokalemia, hypochloremia or hyperbicarbonatemia. This tendency was first documented 60years ago and has subsequently been confirmed in single case reports or small case series, most of which were retrospective. However, this issue has not been addressed analytically. We have therefore systematically reviewed and analyzed the available literature on this subject. Methods: This was a systematic review of the literature. Results: The reports included in this review cover 172 subacute and 90 chronic cases of electrolyte imbalances in patients with cystic fibrosis. The male:female ratio was 1.57. Electrolyte abnormalities were mostly associated with clinically inapparent fluid volume depletion, mainly affected patients aged ≤2.5years, frequently tended to recur and often were found before the diagnosis of cystic fibrosis was established. Subacute presentation often included an history of heat exposure, vomiting, excessive sweating and pulmonary infection. History of chronic presentation, in contrast, was often inconspicuous. The tendency to hypochloremia, hypokalemia and metabolic alkalosis was similar between subacute and chronic patients, with hyponatremia being more pronounced (P

HDMs are a ubiquitous allergen source, with a very well defined biology, but their role in clinical settings and in everyday clinical practice is not well characterized. Aim of this cross-sectional, questionnaire-based study was to assess the clinical characteristics of HDM-related respiratory allergy in a large population of Italian patients.A structured questionnaire was sent to allergists randomly chosen among those of the Italian Federation of Immunology, Allergy and Clinical Immunology (IFIACI). They were asked to fill it with the clinical data of 10-12 consecutive patients referred for respiratory allergy, positive to HDM skin prick test. The questionnaire assessed type and severity of allergy, demographics, yearly distribution of symptoms, treatment, and satisfaction with the therapy.45 allergists collected data from 499 patients. Within the evaluated population, 42% had rhinitis only, 45% asthma + rhinitis and 13% asthma alone. Rhinitis was moderate/severe in 51% of patients. Asthma was intermittent in 36% of patients, mild in 37% and moderate in 27%. Conjunctivitis was the most frequent comorbidity (36%), followed by rhinosinusitis (16%), adenoid hypertrophy (6%) and polyposis (5%). Out of the population, 56.2% of patients were not at all or partially not satisfied of their treatment for rhinitis, whereas the percentage of dissatisfied patients was about 53% for asthma therapy. 34% patients (n = 170) were monosensitized to HDM. It is confirmed that patients have more symptoms during the fall-winter periods.Patients with HDM allergy have frequently moderate-severe rhinitis, and about 50% of them are not satisfied with their treatment.

The aim of this paper was to evaluate the effects of a very long distance swimming task on psychological, biomechanical and physiological responses. Eight swimmers (age 21.0 ± 1.2 years; stature 1.80 ± 0.07 m; body mass 76.7 ± 11.0 kg; means ± SD) participated in a 25-km trial in a swimming pool.Before and immediately after the trial, swimmers underwent a 50-m sprint test, during which we assessed velocity, stroke rate (SR), stroke length (SL) and psychological condition (rate of perceived exertion [RPE] and profile of mood state [POMS] questionnaire). During the 25-km trial we determined also elbow angle, heart rate (HR) and lactate concentration ([La]).Velocity, SR and SL during the sprint test after the trial decreased compared to before from 1.91 ± 0.01 m·s⁻¹, 0.94 ± 0.01 cycles·s⁻¹ and 1.99 ± 0.02 m·cycle⁻¹ to 1.45 ± 0.01 m·s⁻¹, 0.78 ± 0.01 cycles·s⁻¹ and 1.84 ± 0.03 m·cycle⁻¹, respectively (P0.05). During the 25-km trial, velocity and SL decreased significantly, while SR and elbow angle did not change. Velocity and SR during the sprint test after the trial were significantly higher than those during the trial. RPE and fatigue (POMS subscale) increased significantly, while the other negative POMS subscales and vigor decreased significantly. HR decreased significantly at 20 km, then increasing significantly at 25 km, while [La] did not change.These results suggest that, despite the occurrence of fatigue, as evidenced by the drop in velocity and changes in psychological profile, swimmers were able to complete the 25-km trial by adopting a conservative pacing, unveiling also a reserve in maximum performance.

The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of glucose and lipid metabolism. They are activated by natural ligands, such as fatty acids, and are also targets of synthetic antidiabetic and hypolipidemic drugs. By using cell-based reporter assays, we studied the transactivation activity of two enantiomeric ureidofibrate-like derivatives. In particular, we show that the R-enantiomer, (R)-1, is a full agonist of PPARgamma, whereas the S-enantiomer, (S)-1, is a less potent partial agonist. Most importantly, we report the x-ray crystal structures of the PPARgamma ligand binding domain complexed with the R- and the S-enantiomer, respectively. The analysis of the two crystal structures shows that the different degree of stabilization of the helix 12 induced by the ligand determines its behavior as full or partial agonist. Another crystal structure of the PPARgamma.(S)-1 complex, only differing in the soaking time of the ligand, is also presented. The comparison of the two structures of the complexes with the partial agonist reveals significant differences and is suggestive of the possible coexistence in solution of transcriptionally active and inactive forms of helix 12 in the presence of a partial agonist. Mutation analysis confirms the importance of Leu(465), Leu(469), and Ile(472) in the activation by (R)-1 and underscores the key role of Gln(286) in the PPARgamma activity.

Exercise performed at a competitive level could deeply modify the immune system and the cytokine response of athletes. In this report, we demonstrated that young elite female artistic gymnasts (n = 16; age: 9-15 years) showed an increase of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) mRNA expression in blood mononuclear cells (PBMCs), in comparison to girls performing the same sport at a recreational level (n = 16; age: 10-15 years). The increase of IL-6 and TNF-α mRNAs appeared to be directly linked to the intensity and duration of the training. Moreover, in elite athletes engaged in artistic gymnastics or in synchronised swimming (n =34; age: 9-15 years), IL-6 gene expression appeared to be modulated by the levels of circulating oestrogens: pre-pubertal athletes (n = 20; age: 11 ± 1 years) revealed a higher increase in IL-6 than pubertal athletes (n = 14; age: 14 ± 1.6 years). In pre-pubertal athletes, body mass index (BMI) percentile was inversely correlated with the increase of both IL-6 and TNF-α. The consequence of these events was the shift of the cytokine profile towards a pro-inflammatory status. These modifications, induced by training performed at an elite level, might negatively affect the growth of female children athletes.

Abstract We previously reported that mevalonate starvation elicited by hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors reduced cholesterol accumulation promoted in murine macrophages by acetylated LDL (AcLDL). In the present study we investigated the cellular mechanism of this effect. Our results indicate that the HMG-CoA reductase inhibitors fluvastatin and simvastatin reduce, in a concentration-dependent manner, more then 50% of the 125 I-AcLDL degradation by macrophages. This effect was not due to a decrease of lysosomal enzyme activity, and it was paralleled by the retention of AcLDL-associated cholesteryl ester in the incubation medium. The ability of fluvastatin to inhibit AcLDL degradation was completely overcome by mevalonate and its derivative geranylgeraniol. Evaluation at 4°C of 125 I-AcLDL binding to plasma membrane suggested that the inhibitory effect of fluvastatin on lipoprotein catabolism was not due to a decreased expression of scavenger receptors. Fluorescent microscope analysis of cellular internalization of AcLDL labeled with the fluorochrome 3,3′-dioctadecyl indocarbocyanine demonstrated that fluvastatin inhibits lipoprotein endocytosis, an effect reversed by mevalonate. Studies performed with native 125 I-LDL indicated that fluvastatin did not inhibit but rather increased the degradation of LDL taken up by the normal LDL receptor. These results exclude a generalized depression of the cellular endocytotic activity by the drug. The ability of fluvastatin to reduce AcLDL catabolism and cholesterol esterification was more pronounced in cholesterol-enriched macrophages compared with normal cells. In conclusion, the present results demonstrate that HMG-CoA reductase inhibitors may reduce the in vitro cholesterol accumulation in macrophages by inhibiting AcLDL endocytosis.

The worldwide prevalence of allergic diseases such as rhinitis, asthma, and atopic dermatitis is continuously increasing, while other allergic disorders such as urticaria and angioedema are less investigated. We performed a population study evaluating the prevalence of any kind of allergic disorders.The entire population of 7,201 inhabitants of Cotignola (Ravenna, Italy) was surveyed by a questionnaire assessing symptoms related to rhinitis, asthma, anaphylaxis, skin symptoms and insect sting allergy as well as the features of clinical presentations, diagnosis, and treatment received.Valid questionnaires were obtained by 6,676 inhabitants (92.7%). The sample was formed by 3,266 males and 3,495 females, the mean age was 45.6 years; 1,035 subjects (15.5%) were aged less than 18 years; 404 subjects (6%) had at least one episode of wheezing/breathlessness in their lifetime, and 243 of them (60.1%) had a diagnosis of asthma; 1,002 subjects (14.8%) had nose symptoms in their lifetime, and 375 of them (37.4%) had a diagnosis of allergic rhinitis or rhinoconjunctivitis. For other allergic manifestations, data were obtained from 5,730 subjects; of them, 178 (3.1%) had skin symptoms, 59 (1.1%) had oral symptoms, and 37 (0.6%) had anaphylaxis; 207 (3.6%) had reactions to insect stings. There were no significant differences in prevalence between Italians and immigrants. Only 51.7% of subjects with asthma, 46.5% of those with rhinitis, 22.7% of those with other allergies, but 97.1% of those with insect allergy, received treatment.These findings confirm recent data on epidemiology of allergic diseases in Europe, particularly in Italy, and add some details on how such diseases are managed.

Video abstract Video, The house dust mite is a major cause of respiratory allergy worldwide. The management of mite allergy is based on avoidance measures, drug treatment, and allergen immunotherapy, but only allergen immunotherapy is able to modify the natural history of the disease. Injectable subcutaneous immunotherapy was introduced a century ago, while sublingual immunotherapy was proposed in the 1980s and emerged in the ensuing years as an effective and safe option to subcutaneous immunotherapy. However, the quality of the extracts to be used in allergen immunotherapy is crucial for the success of treatment. The mite extract for sublingual immunotherapy known as Staloral 300 was developed to offer optimal characteristics concerning the mite culture medium, standardization, and allergen dose. Double-blind, placebo-controlled trials with Staloral 300 have provided a substantial part of the clinical evidence analyzed in a meta-analysis of the efficacy of allergen immunotherapy in mite-induced rhinitis and asthma. Safety and tolerability are very good, mild local reactions in the mouth being the most common side effect. This makes it feasible to carry out sublingual immunotherapy for the 3–5-year duration needed to achieve long-lasting tolerance to the specific allergen. The performance of Staloral 300 may provide optimal conditions for an effective and safe sublingual immunotherapy in patients with mite-induced respiratory allergy.

Quality of life (QOL) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment. However, there are no data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized patients.To evaluate the effect, in real-life clinical practice, of SLIT on QOL in a population of polysensitized patients with allergic rhinitis.We prospectively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis. QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of SLIT (performed in approximately 70% of cases using single allergen extracts provided by the same manufacturer).The most frequent causes of sensitization were grass pollen, Parietaria, and house dust mites. The mean number of sensitizations per patient was 3.65. SLIT was performed with 1 extract in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items improved significantly (P.01 in all cases), with the following reductions noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to 1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44.This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL.

Polysensitization is quite frequent in allergic children and may cause difficulties for the allergist in prescribing allergen-specific immunotherapy. This study aimed at evaluating the clinical effectiveness of 1 year of sublingual immunotherapy (SLIT) in a cohort of Italian allergic children with polysensitization. This open study was performed on 51 polysensitized children (34 boys; mean age, 11.8 years; range, 5.2-17.7 years) with allergic rhinitis and/or mild to moderate asthma. All of them were treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, the type of diagnosis, the severity of symptoms, and the use of drugs were evaluated at baseline and after 1 year. The adverse events to SLIT were also evaluated. Forty-two children were treated with a single extract, four with two different extracts and three with a mix of allergens. SLIT treatment induced a significant reduction in the number of sensitizations (p = 0.018); significant improvement of allergic rhinitis classification and severity; significant reduction of ocular, nasal, and bronchial symptoms (p < 0.01 for all); and drugs use (p < 0.01 for all drugs). No systemic reactions to SLIT were observed. This open study provides evidence that polysensitization is not an obstacle for prescribing SLIT in polysensitized children. Indeed, SLIT efficacy on clinical parameters is significant after 1 year and the therapy is safe.

Grass pollen is a major cause of allergy throughout the world. The only treatment targeting the causes and not only the symptoms of allergy is specific immunotherapy (IT). A number of controlled trials demonstrated the efficacy of IT in grass pollen allergic subjects, most using extracts of multiple grasses but some using extracts of a single grass. The optimal grass extract for IT has not yet been established.This study is aimed at investigating the IgE-binding pattern in sera from IT-naïve patients from central Italy with allergic rhinitis and/or asthma caused by grass pollen. A 5-grass extract was used (containing Dactylis glomerata, Poa pratensis, Lolium perenne, Antoxanthum odoratum and Phleum pratense) and compared to Phleum pratense alone, which is the most frequently used single grass extract, by the RAST-inhibition technique.The 5-grass extract showed, by RAST-inhibition, a significantly higher binding compared to the Phleum pratense extract for Antoxanthum odoratum and Poa pratensis, while the two extracts for immunotherapy showed similar binding affinity for Phleum pratense and the non-Pooideae grass, Cynodon dactylon.The use of a mixed-grass pollen extract seems to be the optimal choice when applying specific IT in grass pollen-allergic subjects from the Mediterranean area.

Allergic rhinitis and asthma have a very high prevalence and constitute a health problem with a relevant burden of disease, concerning medical and economical issues. Among the treatments of allergy, specific immunotherapy (IT) has the capacity to favourably alter the natural history of the disease both during and after its performance, and thus to reduce the direct and indirect costs of allergic rhinitis and asthma. A number of studies reported a cost reduction for traditional, subcutaneous IT (SCIT). We analyzed the available studies on economic evaluation of sublingual immunotherapy (SLIT) in children and adults. Articles were retrieved from Medline and Embase using the terms economic aspects, pharmacoeconomics, cost effectiveness, and sublingual immunotherapy. 18 articles were found in English language, 7 studies investigated the economic advantage of SLIT over standard drug treatment in subjects with respiratory allergy, and 2 of them included a comparison of costs of SCIT and SLIT. The data obtained provide evidence that SLIT is associated to economic advantages and/or monetary savings, specifically in terms of reduction of economic burden of the disease. Although the number of studies is still limited, the available data support a SLIT effect on sparing costs for respiratory allergy.

Polysensitization is very common in allergic patients and was previously reported to be associated with more severe symptoms and impaired quality of life. Polysensitization is often considered as a contraindication for specific immunotherapy (SIT). This study is aimed at evaluating the allergist attitude for decision making in choosing SIT in a cohort of Italian polysensitized patients. Moreover, the 1-year effectiveness of the prescribed sublingual immunotherapy (SLIT) in this cohort was evaluated. The study was performed on 244 patients (109 males, 135 females, mean age 28.7 years, S.D. 12.0) with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA criteria) treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, type of diagnosis, severity of symptoms, use of drugs, and adverse events were evaluated at baseline and after 1 year. A total of 230 patients were treated with SLIT: 165 with a single extract, and 65 with two different extracts (mix). SLIT treatment significantly improved disease staging, and reduced symptom severity and drug use. No systemic reaction was reported. In conclusion, these findings provide preliminary evidence that SIT is effective and safe in polysensitized patients after 1 year of treatment also using single extracts, and thus does not represent an obstacle for prescribing SIT.

Objective Inflammation might represent a second hit for anti-phospholipid antibody (aPL)-mediated thrombosis. Inflammatory responses have been linked to gene polymorphisms of several cytokines and Toll Like Receptors (TLRs). We examined IL1β, TNFα, TGFβ, IL6, IFNγ, IL10, tlr4 gene polymorphisms in a family with several members positive for IgG anti-β2 glycoprotein I (β2GPI) antibodies but with recurrent thrombosis in one member only. Methods Lupus anticoagulant, anti-cardiolipin, anti-β2GPI IgG/IgM antibodies, IL1β, TNFα, TGFβ1, IL6, IL10, IFNγ, tlr4 gene polymorphisms (by allele-specific polymerase chain reaction) in addition to standard thrombophilic risk factors and cytokine serum levels (IL-1β, TNFα, IL-10) were evaluated. Results Recurrent thrombotic events was reported only in the proband, but not in three healthy siblings persistently positive for IgG anti-β2GPI antibodies, respectively. The wild type tlr4 gene and cytokine polymorphisms associated with a high pro-inflammatory response (IL-1β promoter-511 C/T; TNFα G/A; TGFβ + 10 T/C, +25 C/G; IL-6 −174 C/G) were found only in the proband. Serum cytokine levels were normal. Conclusion This case report confirms that protective tlr4 gene polymorphisms are more frequent in asymptomatic aPL carriers. In line with the role of inflammatory mediators as second hits for aPL-associated thrombosis, the polymorphisms of cytokines linked to higher inflammatory response were found in the proband only.

Anti-phospholipid antibodies (aPL) are risk factor for recurrent pregnancy loss and obstetrical complications. The mechanisms of aPL-mediated pregnancy failure are still a matter of research. Although aPL are associated with thrombosis, thrombotic events cannot explain all the miscarriages. There is evidence for a direct in vitro aPL effect on the trophoblast as shown by their binding; reduction of proliferation, human chorionic gonadotrophin release, in vitro invasiveness, adhesion molecule expression; and increased apoptosis. Such a direct reactivity is supported by the expression of beta2 glycoprotein (beta 2GP) I on trophoblast cell membranes. aPL/anti-beta 2GPI antibodies also bind to human decidual/endometrial cells in vitro and induce a pro-inflammatory phenotype. APL-mediated inflammatory processes at the placental level are apparently responsible for fetal loss at least in animal models. Both complement activation and pro-inflammatory cytokine/chemokine secretion have been shown to play a role. More recently, complement-induced tissue factor expression on infiltrating neutrophils was described as an additional pathogenic mechanisms mediated by aPL. As a whole, these findings do suggest that aPL may induce a defective placentation by acting at different levels without involving necessarily thrombotic events.

The clinical expression of the most common allergic diseases reflects allergic inflammation and underlines that inflammation is the main target of anti-allergic therapies. Allergen specific immunotherapy (AIT) has a recognized impact on allergic inflammation, which persists after its discontinuation, and is the only therapy able to modify the natural history of allergic march. The traditional, subcutaneous route of administration is effective in altering the phenotype of allergen-specific T cells, switching from a Th2-type response, characterized by the production of IL-4, IL-5, IL-13, IL-17, and IL-32 cytokines to a Th1-type response. This immune deviation is related to an increased IFN-gamma and IL-2 production as well as to the anergy or tolerance of Th2, the latter related to the generation of allergen-specific T regulatory (Treg) cells, which produce cytokines such as IL-10 and TGF-beta. Anti-inflammatory mechanisms observed during sublingual IT with high allergen doses proved to be similar compared to subcutaneous immunotherapy. Recent data obtained in biopsies clearly indicate that the pathophysiology of the oral mucosa, and in particular mucosal dendritic cells, plays a pivotal role in inducing tolerance to the administered allergen.