MRgFUS thalamotomy for the treatment of tremor: evaluation of learning curve and operator's experience impact on the procedural and clinical outcome.

BACKGROUND: MRgFUS Vim ablation is increasingly used for the treatment of tremor in ET e PD patients but there is little published research on the importance of operator experience in this procedure. This study aims to evaluate the learning curve and the influence of the operator experience on the procedural and clinical outcomes. METHODS: We retrospectively evaluated 90 patients (38 ET, 52 PD) submitted to MRgFUS unilateral thalamotomy in the period between February 2018 and July 2020. Clinical endpoints, procedural times, and technical parameters were recorded in all procedures. Based on the time of treatment, patients were divided into three groups of 30 units each, comparing all variables between each time period group. RESULTS: In Group A, the average patient preparation time was 120.6 min, the treatment time was 105.2 min, the number of was sonications 14.1, and the mean target shifts 3.1. In Group B, the mean preparation time was 105.5 min, the treatment time was 89.5 min, the number of sonications was 13.2, and the target shifts 3.0. Group C showed inferior values of preparation time (101.9 min), treatment time (71.7 min), numbers of sonications (10.6), and shifts (1.7). Thalamotomy-related complications occurred in 9 patients of Group A, 2 of Group B, and 5 of Group C. Tremor relapse occurred in 7 patients of Group A, 3 of Group B, and 2 of Group C. The days of hospitalization were comparable in the three groups. CONCLUSIONS: The operators experience is associated with the improvement of clinical and procedural outcome in MRgFUS thalatomy for the treatment of ET and PD tremor.

Liposomes embedded with differentiating factors as a new strategy for enhancing DPSC osteogenic commitment.

Human dental pulp stem cell (DPSC) differentiation toward the osteoblastic phenotype is enhanced when culture media are supplemented with differentiating factors, i.e. ascorbic acid, ß-glycerophosphate and dexamethasone. Liposomes, spherical vesicles formed by a phospholipid bilayer, are frequently used as carriers for drugs, growth factors and hydrophobic molecules. The aim of this work was to speed up DPSC commitment to the osteogenic lineage by embedding differentiating factors within liposomes. Firstly, liposomes were prepared by rehydrating a phospholipidic thin film and characterised in terms of dimensions. Secondly, liposome-exposed DPSCs were characterised by their immunophenotypic profile. Levels of CD90 were significantly decreased in the presence of liposomes filled with ascorbic acid, ß-glycerophosphate and dexamethasone (Lipo-Mix) with respect to normal differentiation medium (DM), while CD73 and CD29 expression were enhanced, suggesting osteogenic commitment. Additionally, an appreciable extracellular matrix deposition is detected. Thirdly, the Lipo-Mix formulation better increases alkaline phosphatase activity and levels of Collagen I secretion with respect to DM. In parallel, the new liposome formulation is capable of decreasing the release of H2O2 and of triggering a precocious antioxidant cell response, redressing the redox balance required upon mesenchymal stem cell commitment to osteogenesis. It can be therefore hypothesised that Lipo-Mix could represent a suitable tool for clinical regenerative purposes in the field of tissue engineering by speeding up DPSC osteogenic commitment, mineralised matrix deposition and remodelling.

Inhomogeneity of charge-density-wave order and quenched disorder in a high-Tc superconductor.

It has recently been established that the high-transition-temperature (high-Tc) superconducting state coexists with short-range charge-density-wave order and quenched disorder arising from dopants and strain. This complex, multiscale phase separation invites the development of theories of high-temperature superconductivity that include complexity. The nature of the spatial interplay between charge and dopant order that provides a basis for nanoscale phase separation remains a key open question, because experiments have yet to probe the unknown spatial distribution at both the nanoscale and mesoscale (between atomic and macroscopic scale). Here we report micro X-ray diffraction imaging of the spatial distribution of both short-range charge-density-wave 'puddles' (domains with only a few wavelengths) and quenched disorder in HgBa2CuO4 + y, the single-layer cuprate with the highest Tc, 95 kelvin (refs 26-28). We found that the charge-density-wave puddles, like the steam bubbles in boiling water, have a fat-tailed size distribution that is typical of self-organization near a critical point. However, the quenched disorder, which arises from oxygen interstitials, has a distribution that is contrary to the usually assumed random, uncorrelated distribution. The interstitial-oxygen-rich domains are spatially anticorrelated with the charge-density-wave domains, because higher doping does not favour the stripy charge-density-wave puddles, leading to a complex emergent geometry of the spatial landscape for superconductivity.

Age is not the only risk factor in COVID-19: the role of comorbidities and of long staying in residential care homes.

BACKGROUND: The actual SARS-CoV-2 outbreak caused a highly transmissible disease with a tremendous impact on elderly people. So far, few studies focused on very elderly patients (over 80 years old). In this study we examined the clinical presentation and the outcome of the disease in this group of patients, admitted to our Hospital in Rome. METHODS: This is a single-center, retrospective study performed in the Sant'Andrea University Hospital of Rome. We included patients older than 65 years of age with a diagnosis of COVID-19, from March 2020 to May 2020, divided in two groups according to their age (Elderly: 65-80 years old; Very Elderly > 80 years old). Data extracted from the each patient record included age, sex, comorbidities, symptoms at onset, the Pneumonia Severity Index (PSI), the ratio of the partial pressure of oxygen in arterial blood (PaO2) to the inspired oxygen fraction (FiO2) (P/F) on admission, laboratory tests, radiological findings on computer tomography (CT), length of hospital stay (LOS), mortality rate and the viral shedding. The differences between the two groups were analyzed by the Fisher's exact test or the Wilcoxon signed-rank test for categorical variables and the Mann-Whitney U test for continuous variables. To assess significance among multiple groups of factors, we used the Bonferroni correction. The survival time was estimated by Kaplan-Meier method and Log Rank Test. Univariate and Multivariate logistic regression were performed to estimate associations between age, comorbidities, provenance from long-stay residential care homes (LSRCH) s and clinical outcomes. RESULTS: We found that Very Elderly patients had an increased mortality rate, also due to the frequent occurrence of multiple comorbidities. Moreover, we found that patients coming from LSRCHs appeared to be highly susceptible and vulnerable to develop severe manifestations of the disease. CONCLUSION: We demonstrate that there were considerable differences between Elderly and Very Elderly patients in terms of inflammatory activity, severity of disease, adverse clinical outcomes. To establish a correct risk stratification, comorbidities and information about provenience from LSRCHs should be considered.

Ventilation and air cleaning to limit aerosol particle concentrations in a gym during the COVID-19 pandemic.

SARS-CoV-2 can spread by close contact through large droplet spray and indirect contact via contaminated objects. There is mounting evidence that it can also be transmitted by inhalation of infected saliva aerosol particles. These particles are generated when breathing, talking, laughing, coughing or sneezing. It can be assumed that aerosol particle concentrations should be kept low in order to minimize the potential risk of airborne virus transmission. This paper presents measurements of aerosol particle concentrations in a gym, where saliva aerosol production is pronounced. 35 test persons performed physical exercise and aerosol particle concentrations, CO2 concentrations, air temperature and relative humidity were obtained in the room of 886 m³. A separate test was used to discriminate between human endogenous and exogenous aerosol particles. Aerosol particle removal by mechanical ventilation and mobile air cleaning units was measured. The gym test showed that ventilation with air-change rate ACH = 2.2 h-1, i.e. 4.5 times the minimum of the Dutch Building Code, was insufficient to stop the significant aerosol concentration rise over 30 min. Air cleaning alone with ACH = 1.39 h-1 had a similar effect as ventilation alone. Simplified mathematical models were engaged to provide further insight into ventilation, air cleaning and deposition. It was shown that combining the above-mentioned ventilation and air cleaning can reduce aerosol particle concentrations with 80 to 90% , depending on aerosol size. This combination of existing ventilation supplemented with air cleaning is energy efficient and can also be applied for other indoor environments.

The functioning side of the pancreas: a review on insulinomas.

PURPOSE: Insulinomas are a rare type of neuroendocrine tumors, originating in the pancreas, difficult to diagnose and to treat. Due to its rarity, insulinomas are a not well-known pathological entity; thus, the diagnostic process is frequently a medical challenge with many possible differential diagnoses. The diagnostic process varies between non-invasive procedures, such as the fasting test or imaging techniques, and invasive ones. Insulinomas are rarely malignant, but the glycemic imbalance correlated with this tumor can frequently alter the quality of life of the patients and the consequent hypoglycemia can be extremely dangerous. Moreover, insulinomas can be associated with different genetic syndromes, such as Multiple Endocrine Neoplasia 1, accompanied by other specific symptoms. There are many different treatment strategies, depending on the need to control symptoms or control diseases progression, the only curative one being surgery. METHODS AND RESULTS: We reviewed the evidences present in the literature on insulinomas and reported its main clinical characteristics and management strategies. CONCLUSION: The aim of this review of the literature is to present the current knowledge on insulinomas, exploring the main clinical characteristics, the diagnostic tools, and the therapeutic strategies.

Short communication: Economic impact among 7 reproductive programs for lactating dairy cows, including a sensitivity analysis of the cost of hormonal treatments.

Although hormonal synchronization programs can improve reproductive efficiency of dairy herds, some farmers question the economics of these programs based on the upfront cost of hormonal treatments as opposed to the economic value of the resulting reproductive performance. Our aim was to compare the economic impact of reproductive management programs that incorporate varying degrees of detection of estrus and timed artificial insemination (AI) in dairy herds with year-round calving in confinement total mixed ration systems. A reproductive economic analysis simulation model was used to compare the economic impact of pairs of reproductive management programs. We simulated sets of scenarios for 2 analyses. In the first analysis, we calculated the economic impact of switching from a Presynch-Ovsynch program to a Double-Ovsynch program that included a second PGF2α treatment during the Breeding-Ovsynch portion of the program (Double-Ovsynch+PGF). In the second analysis, we conducted a break-even analysis in which the cost of hormonal treatments was incrementally increased within various reproductive management programs. Our analyses revealed that a Double-Ovsynch+PGF program, the most intensive program evaluated, was more profitable than other programs compared, including a Presynch-Ovsynch program with 100% timed AI or a Presynch-Ovsynch program that incorporated detection of estrus, despite the higher upfront cost incurred by using more hormonal treatments. This advantage remained until the cost of hormones was increased 5 to 14 times current US market prices and 2 to 6 times current European market prices. The cost of GnRH had a greater impact on net profit gain than the cost of PGF2α. In conclusion, more intensive reproductive programs that use more hormonal treatments but result in substantially increased reproductive performance are more profitable than less intensive programs and remain so even if hormone prices are unusually high.

Should omalizumab be used in severe asthma/COPD overlap?

A large number of patients suffering from asthma or chronic obstructive pulmonary disease (COPD) can show overlapping features of both diseases. Several subjects affected by asthma-COPD overlap (ACO) may be at a severe stage, poorly responsive to triple therapy including inhaled corticosteroids, long-acting ß2 agonists and muscarinic antagonists. This review tries to explore whether omalizumab can be used in poorly controlled severe ACO patients. According to the few studies available, omalizumab may improve asthma outcomes in ACO, although the magnitude of improvements may be lower in comparison to those obtained in subjects affected only by severe asthma. Omalizumab, by acting on IgE, might improve the eosinophilic pattern which is characteristic of the ACO asthma inflammation component. It can be hypothesized that a prevalence of Th1/Th17 airway inflammation pathways can modulate a lower response to anti-IgE while a Th2 pattern can lead to a higher effectiveness to omalizumab in ACO. High levels of IgE, FeNO and blood eosinophil count may be markers of a better response to omalizumab. In conclusion, on the basis of the few studies available, omalizumab could be effective in poorly-controlled severe ACO, although to a reduced extent in comparison to patients affected only by asthma.

Food Safety Issues Related to Uses of Insects for Feeds and Foods.

Edible insects are expected to become an important nutrient source for animals and humans in the Western world in the near future. However, before insects can be put on the market, the safety of their use for feed and food is warranted. This literature study was prepared to provide an overview of the actual knowledge of possible food safety hazards, including chemical, microbiological, and allergenic agents and prions, to human and animal health upon the use of insects for food and feed, and to highlight data gaps and suggest the way forward. From the data available, heavy metals of concern are cadmium in black soldier fly and arsenic in yellow mealworm larvae. Investigated mycotoxins do not seem to accumulate. Residues of pesticides, veterinary drugs, and hormones, as well as dioxins and PCBs, are sometimes found in insects. Contamination of insects with pathogens to human health is a consequence of a combination of the substrates used and the farming and processing steps applied. Insects harbor a wide variety of microorganisms, and some human pathogenic bacteria may be present. In addition, insects may harbor and transmit parasites. There is no evidence so far insects may harbor pathogenic viruses or prions, but they may act as vectors. Insects and insect-derived products may have allergenic potential. In this review, evidence on some safety aspects is displayed, and data gaps are identified. Recommendations are given for future research to fill the most relevant data gaps.

Evaluation of equine oocyte developmental competence using polarized light microscopy.

The purpose of this study was to observe in vitro-matured equine oocytes with an objective computerized technique that involves the use of a polarized light microscope (PLM) in addition to the subjective morphological evaluation obtained using a classic light microscope (LM). Equine cumulus-oocyte complexes (COCs, n = 922) were subjected to different in vitro maturation times (24, 36 or 45 h), however, only 36-h matured oocytes were analyzed using CLM. The 36-h matured oocytes that reached maturity were parthenogenetically activated to evaluate the quality and meiotic competence. Average maturation percentages per session in groups 1, 2 and 3 (24-, 36- and 45-h matured oocytes respectively) were 29.31 ± 13.85, 47.01 ± 9.90 and 36.62 ± 5.28%, whereas the average percentages of immature oocytes per session were 28.78 ± 20.17, 7.83 ± 5.51 and 22.36 ± 8.39% respectively. The zona pellucida (ZP) birefringent properties were estimated and correlated with activation outcome. ZP thickness and retardance of the inner layer of the zona pellucida (IL-ZP) were significantly increased in immature oocytes compared with mature oocytes (P < 0.001 and P < 0.01 respectively). The comparison between parthenogenetically activated and non-activated oocytes showed a significant increase in the area and thickness of the IL-ZP in parthenogenetically activated oocytes (P < 0.01). These results show that the 36-h in vitro maturation (IVM) protocol allowed equine oocytes to reach maturity, and PLM observation of ZP can be used to distinguish mature and immature oocytes as well as activated and non-activated oocytes.

Rise Time Reduction of Thermal Actuators Operated in Air and Water through Optimized Pre-Shaped Open-Loop Driving.

Electrothermal actuators have many advantages compared to other actuators used in Micro-Electro-Mechanical Systems (MEMS). They are simple to design, easy to fabricate and provide large displacements at low voltages. Low voltages enable less stringent passivation requirements for operation in liquid. Despite these advantages, thermal actuation is typically limited to a few kHz bandwidth when using step inputs due to its intrinsic thermal time constant. However, the use of pre-shaped input signals offers a route for reducing the rise time of these actuators by orders of magnitude. We started with an electrothermally actuated cantilever having an initial 10-90% rise time of 85 µs in air and 234 µs in water for a standard open-loop step input. We experimentally characterized the linearity and frequency response of the cantilever when operated in air and water, allowing us to obtain transfer functions for the two cases. We used these transfer functions, along with functions describing desired reduced rise-time system responses, to numerically simulate the required input signals. Using these pre-shaped input signals, we improved the open-loop 10-90% rise time from 85 µs to 3 µs in air and from 234 µs to 5 µs in water, an improvement by a factor of 28 and 47, respectively. Using this simple control strategy for MEMS electrothermal actuators makes them an attractive alternative to other high speed micromechanical actuators such as piezoelectric stacks or electrostatic comb structures which are more complex to design, fabricate, or operate.

Characterization of luteal dynamics in lactating Holstein cows for 32 days after synchronization of ovulation and timed artificial insemination.

Approximately 20 to 30% of cows diagnosed not pregnant 32 d after timed artificial insemination (TAI) lack a corpus luteum (CL), and cows submitted to a resynchronization protocol in the absence of a CL have about 10% fewer pregnancies per AI (P/AI) than cows with a CL. An understanding of luteal dynamics after synchronization of ovulation and TAI may help refine strategies for reinseminating cows failing to conceive. Lactating Holstein cows (n = 141) were synchronized for first TAI using a Double-Ovsynch protocol. Thrice weekly from 4 to 32 d after TAI, blood samples were collected for evaluation of plasma progesterone (P4) concentrations, and CL diameter was measured using transrectal ultrasonography. Pregnancy status was determined using transrectal ultrasonography 32 d after TAI. Nonsynchronized cows (n = 4) were removed from the study. For cows diagnosed pregnant 32 d after TAI (n = 57), P4 increased from 4 to 15 d and then remained constant until 32 d after TAI, whereas CL volume increased from 4 to 11 d and then remained constant until 32 d after TAI. For cows diagnosed not pregnant 32 d after TAI (n = 80), P4 profiles were evaluated using statistical cluster analysis based on the day after TAI that P4 decreased to <1 ng/mL, resulting in 5 clusters: (1) CL regression 15 d after TAI (1.3%), (2) CL regression 18 to 22 d after TAI (55.0%), (3) CL regression 25 to 27 d after TAI (17.5%), (4) CL regression 29 to 32 d after TAI (5.0%), and (5) CL maintained until 32 d after TAI (21.3%). Plasma pregnancy-associated glycoprotein (PAG) levels at 25 and 32 d after TAI differed among clusters and were below the cut-off value of the assay for the classification of cows as not pregnant for cows in clusters 2, 3, and 4, whereas more than half of the cows in cluster 5 had increased plasma PAG levels. We conclude that at least half of the nonpregnant cows that maintained their CL until 32 d after TAI were initially pregnant but underwent early pregnancy loss based on increased plasma PAG levels at 25 and 32 d after TAI.

The flux dynamics behavior of the two competing high temperature superconducting phases in underdoped LaCuO4.06.

In complex transition metal oxides (TMO) an arrested electronic phase separation (PS) appears by tuning the system near a Lifshitz transition in multiband Hubbard models. The PS in La2CuO4+y near insulator to metal transition (IMT) is made of short range Charge Density Wave (CDW) order inhomogeneity coexisting with quenched lattice disorder. While at high doping y = 0.1 percolation gives a single superconducting phase, near the IMT at y = 0.06 two coexisting superconducting phases appear: the first one with a critical temperature Tc1 = 16 K and the second one with Tc2 = 29 K. It is known that the two superconducting phases are characterized by two different space geometry because of two different spatial distributions of both CDW order and dopants self-organization. Here we show that these two phases show different flux dynamic regimes using alternating current (AC) multi-harmonic susceptibility experiments. This is a unique technique capable to investigate multi-phase superconductors and characterize their transport properties in a percolative scenario. Results point out that the low critical temperature phase is well described by a bulk-like flux pinning with a 2D geometry while the phase with higher critical temperature shows a 'barrier pinning' mechanism providing direct evidence of two different superconducting vortex dynamics in different complex geometrical spaces.

Cross-reactivity and Tolerability of Ertapenem in Patients With IgE-Mediated Hypersensitivity to ß-Lactams.

BACKGROUND AND OBJECTIVE: Administration of carbapenems to ß-lactam-allergic patients has always been considered potentially harmful because of a 47.4% rate of cross-reactivity to imipenem reported in a single study. Nevertheless, recent studies have shown that the rate of cross-reactivity of imipenem and meropenem with penicillins is lower than 1%. The aim of this study was to evaluate the possibility of using ertapenem in patients with an established IgE-mediated ß-lactam allergy. PATIENTS AND METHODS: We studied all participants who came to our allergy unit and had a clinical history of immediate hypersensitivity reactions to ß-lactams. The inclusion criteria were a positive skin test result to at least 1 ß-lactam molecule and/or positive specific IgE (when available). All participants underwent immediate-type skin tests with several ß-lactam molecules including ertapenem. Challenges with intravenous ertapenem were performed on 2 different days in patients with negative skin test results. RESULTS: We examined 49 patients with a clinical history of immediate reactions to ß-lactams. All the patients had positive skin tests and/or positive specific IgE to at least 1 ß-lactam reagent and negative carbapenem skin tests. Thirty-six patients agreed to undergo the challenges and 35 tolerated the full dose of ertapenem. CONCLUSIONS: The practice of avoiding carbapenems in patients with ß-lactam allergy should be abandoned considering the very low rate of cross-reactivity. ß-Lactam-allergic patients who need ertapenem therapy should undergo skin tests and, if negative, a graded challenge to assess tolerability.

Endoscopic dacryocystorhinostomy with and without silicone intubation: 4 years retrospective study.

The objective of this study is to assess different outcomes between endoscopic dacryocystorhinostomy (En-DCR) with and without silicone intubation. We retrospectively analyzed 84 patients (89 procedures), suffering from chronic epiphora for primary acquired nasolacrimal duct obstruction, treated with En-DCR and divided into two groups depending on silicone stent intubation. The surgical outcomes were evaluated at 7 post-operative controls using Munk's score criteria. Functional success was defined as absence of epiphora, no further episodes of dacryocystitis, and a patent ostium after fluorescein irrigation. 45 En-DCR with stent and 44 En-DCR without stent were performed. Success rate after 18 months follow-up were, respectively, 82.2 % in the stent group and 88.6 % in the non-stent group (OR 0.59) with no statistical differences. The ostial size reduction has been reported in higher percentage in the stent group, mainly due to peristomal granuloma (OR 3.64), scar tissue formation (OR 2.25), and turbinoseptal synaechia (OR 1.76). The benefits of non-intubation are less patient discomfort, reduced surgical time and costs, simpler follow-up regimen and less intubation-associated complications. En-DCR without silicone stent intubation should be the first choice of procedure, stent intubation should be reserved in selected cases with poor local conditions pre and intra-operatively assessed.

Worry and anger rumination in fibromyalgia syndrome.

The aim of the present study was twofold: 1) to investigate the psychological profile of patients with fibromyalgia syndrome (FS) as compared to patients with other chronic pain syndromes (CP) and healthy subjects (HS); 2) to examine the associations between anxiety, depression, worry and angry rumination in FS patients. FS patients (N=30), CP patients (N=30) and HS (N=30) completed measurements of anxiety, depression, worry and angry rumination. FS patients showed higher levels of state and trait anxiety, worry and angry rumination than CP patients and HS, and higher levels of depression than HS. Worry and angry rumination were strongly associated in the FS group. FS patients may use worry and rumination as coping strategies to deal with their negative emotional experience, which might impair their emotional wellbeing. Findings from the present study add to our understanding of the psychological profile of FS patients, and have important implications for developing a tailored CBT protocol for pain management in FS patients.

TRYPTASE AND HISTAMINE MAY SUPPORT ORAL FOOD CHALLENGE IN THE DIAGNOSIS OF ALLERGY.

Allergen-specific immunoglobulin E (IgE) reactions lead to acute degranulation of mast cells and basophils and release of stored mediators, particularly tryptase and histamine, which can be measured in vitro after reactions. The aim of this study was to investigate the utility of serum tryptase and plasma histamine during oral food challenge (OFC) in 103 children with suspected food allergy, in order to support the diagnosis of a IgE-mediated reaction. Blood samples for serum tryptase and plasma histamine were collected before the OFC and after the onset of allergic symptoms or after 60 minutes from test completion. Serum tryptase and plasma histamine were measured by a fluoroenzyme immunoassay (ImmunoCAP; ThermoFisher, Uppsala, Sweden) according to the manufacturer’s instructions. A correlation between serum tryptase and plasma histamine distributions was observed after OFC (p=0.0035). A correlation was also observed for both serum tryptase and plasma histamine before and after OFC (p less than0.0001). Subjects with positive response to OFC had significantly higher values (p = 0.0375) of serum tryptase compared to subjects with negative response. The plasma histamine distribution showed a significant difference between measurements before and after OFC, both in the complete population (p less than 0.0001), and considering the response (negative OFC: p less than 0.0001; positive OFC: p=0.0181). The diagnostic work-up of IgE- mediated food allergy may include determination of serum tryptase and plasma histamine, in order to support the results of OFC. These markers are strongly related to the same IgE-mediated mechanism and, as they can be both easily measured, can confirm the allergic nature of a reaction in the real-life setting of food allergy.

ATOPIC DERMATITIS: IS THERE A ROLE FOR PROBIOTICS?

Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly presents during early childhood. In the last decades the prevalence of AD has increased, especially in western societies. This frequently relapsing inflammatory condition has a strong impact on the quality of life of patients and families. The recent advances in the understanding of this disease have paved the way for the development of new strategies for the prevention and treatment of AD. Among the new therapeutic options, there is increasing interest in the potential benefit of probiotic supplementation. It has been widely demonstrated that the human microbiota plays a fundamental role not only in the maintenance of intestinal homeostasis through the interaction between microorganisms and the innate immune system, but also in the microbiota-mediated development of adaptive immunity. In addition, several studies have demonstrated that probiotics are able to influence the composition of gut microbiota and may exert immunomodulatory effects. According to these promising results, the possible application of probiotics in the therapeutic management of allergic diseases has been investigated in many studies. In particular, a considerable body of literature has been published analyzing the effects of probiotics on patients with AD. In order to shed light on frequently conflicting results, we reviewed the data regarding the application of probiotics in AD, with the aim to provide a state-of-the-art assessment of the most important studies exploring the role of probiotics both in the prevention and treatment of AD.

CYSTIC FIBROSIS AND ANTIBIOTIC HYPERSENSITIVITY: PRESENT KNOWLEDGE AND PRACTICAL APPROACH.

Cystic fibrosis is one of the most common fatal genetic diseases (1 in 2500 births). The defect causing the disease is localized on the 7q31 gene, which codifies for the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) transmembrane protein. CFTR is a chloride channel localized on the epithelial cells of the mucosa of the respiratory tract, pancreatic ducts, biliary tree, intestine, vas deferens and sweat glands. More than 2000 different mutations are currently known; some are prominent or relatively frequent, ranging from one population to another. The most frequent complications of cystic fibrosis are those affecting the bronchial tree. Patients suffer from recurrent lung infections, which involve a progressive loss of lung function. The pulmonary infections are frequent or chronic and limit the quality of life of patients. In addition to being enormously exposed to antibiotics, they have many more opportunities to develop hypersensitivity reactions to these molecules. Only a complete allergy work-up with a detailed analysis of the clinical history, skin tests and provocation test can show if the patient has actually experienced an allergic hypersensitivity reaction. Desensitization is to be considered as a treatment that may help patients benefit from antibiotic treatment in those cases in which they have a proven allergy to a certain molecule.

EMERGING AND FUTURE THERAPIES FOR ALLERGIC RHINITIS.

Allergic rhinitis (AR) is one of the most common diseases and represents a global health problem, currently affecting up to 30% of the general population, with a continuously increasing prevalence and significant comorbidities and complications. To date, the mainstay of current treatment strategies of AR includes allergen avoidance, pharmacotherapy and allergen-specific immunotherapy, as defined by Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines for both adults and children. The aim of this review is to provide an update on all emerging and future therapeutic options for the treatment of AR.