Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Hymenoptera Venom Allergy: Management of Children and Adults in Clinical Practice.

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care.

Molecular diagnostics improves diagnosis and treatment of respiratory allergy and food allergy with economic optimization and cost saving.

BACKGROUND: Component resolved diagnosis (CRD) allows to precisely identify the sensitization to specific molecules of a given allergenic source, resulting in an important improvement in clinical management, particularly of polysensitized subjects. This will end in the correct prescription of allergen immunotherapy (AIT) for respiratory allergy and in adequate avoidance diets or prescription of self-injectable adrenaline in food allergy. OBJECTIVE: The aim of this multicenter, real life study is to evaluate the percentage change of the diagnostic-therapeutic choice in polysensitized patients with respiratory allergy and in patients with food allergy, after using CRD compared to a first level diagnosis, along with an economic analysis of the patient's overall management according to the two different approaches. METHODS: An overall number of 462 polysensitized patients, as suggested by skin prick tests (SPT), and with clinical symptoms related to a respiratory (275 pts) or food (187 pts) allergy, were recruited. All patients underwent CRD for specific IgE against food or inhalant recombinant molecules, which were chosen according to medical history and positivity to SPT. The first diagnostic-therapeutic hypothesis, based only on medical history and SPT, was recorded for each patient while the final diagnostic-therapeutic choice was based on the results from CRD. The rate of change of the diagnostic-therapeutic choice from the first hypothesis to the final choice was statistically evaluated. The economic impact of CRD on the overall management of the allergic patients was analyzed to evaluate whether the increase in the diagnostic costs would be compensated and eventually exceeded by savings coming from the improved diagnostic-therapeutic appropriateness. RESULTS: An approximate 50% change (k index 0.54) in the prescription of AIT for respiratory allergy as well as a change in the prescription of self-injectable adrenaline (k index 0.56) was measured; an overall saving of financial resources along with a higher diagnostic-therapeutic appropriateness was also detected. CONCLUSION: There is moderate agreement concerning prescription of AIT and self-injectable adrenaline before and after performing CRD: this highlights the usefulness of CRD, at least in polysensitized patients, in indicating the risk assessment and therefore the correct therapy of respiratory and food allergy, which results in a cost-saving approach.

Clinical approach on challenge and desensitization procedures with aspirin in patients with ischemic heart disease and nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, this study aimed to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. METHODS: Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel. RESULTS: Altogether, 310 subjects were assessed; 217 had histories of urticaria/angioedema, 50 of anaphylaxis, 26 of nonimmediate cutaneous eruptions, and 17 of bronchospasm related to ASA/nonsteroidal anti-inflammatory drugs (NSAID) intake. Specifically, 119 subjects had index reactions to ASA doses lower than 300 mg. Of the 310 subjects, 138 had an acute coronary syndrome (ACS), 101 of whom underwent desensitizations, whereas 172 suffered from a chronic ischemic heart disease (CIHD), 126 of whom underwent challenges. Overall, 163 subjects underwent challenges and 147 subjects underwent desensitizations; 86 of the latter had index reactions to ASA doses of 300 mg or less. Ten subjects reacted to challenges, seven at doses up to 500 mg, three at a cumulative dose of 110 mg. The desensitization failure rate was 1.4%. CONCLUSIONS: In patients with stable CIHD and histories of nonsevere hypersensitivity reactions to ASA/NSAIDs, an ASA challenge is advisable. Patients with an ACS and histories of hypersensitivity reactions to ASA, especially following doses lower than 100 mg, should directly undergo desensitization.

A Computational Tool for the Microstructure Optimization of a Polymeric Heart Valve Prosthesis.

Styrene-based block copolymers are promising materials for the development of a polymeric heart valve prosthesis (PHV), and the mechanical properties of these polymers can be tuned via the manufacturing process, orienting the cylindrical domains to achieve material anisotropy. The aim of this work is the development of a computational tool for the optimization of the material microstructure in a new PHV intended for aortic valve replacement to enhance the mechanical performance of the device. An iterative procedure was implemented to orient the cylinders along the maximum principal stress direction of the leaflet. A numerical model of the leaflet was developed, and the polymer mechanical behavior was described by a hyperelastic anisotropic constitutive law. A custom routine was implemented to align the cylinders with the maximum principal stress direction in the leaflet for each iteration. The study was focused on valve closure, since during this phase the fibrous structure of the leaflets must bear the greatest load. The optimal microstructure obtained by our procedure is characterized by mainly circumferential orientation of the cylinders within the valve leaflet. An increase in the radial strain and a decrease in the circumferential strain due to the microstructure optimization were observed. Also, a decrease in the maximum value of the strain energy density was found in the case of optimized orientation; since the strain energy density is a widely used criterion to predict elastomer's lifetime, this result suggests a possible increase of the device durability if the polymer microstructure is optimized. The present method represents a valuable tool for the design of a new anisotropic PHV, allowing the investigation of different designs, materials, and loading conditions.

Structural changes of block copolymers with bi-modal orientation under fast cyclical stretching as observed by synchrotron SAXS.

Load-bearing tissues are composite materials that depend strongly on anisotropic fibre arrangement to maximise performance. One such tissue is the heart valve, with orthogonally arranged fibrosa and ventricularis layers. Their function is to maintain mechanical stress while being resilient. It is postulated that while one layer bears the applied stress, the orthogonal layer helps to regenerate the microstructure when the load is released. The present paper describes changes in the microstructure of a block copolymer with cylindrical morphology, having a bio-inspired microstructure of anisotropic orthogonally oriented layers, under uniaxial strain. To allow structural observations during fast deformation, equivalent to the real heart valve operation, we used a synchrotron X-ray source and recorded 2D SAXS patterns in only 1 ms per frame. The deformation behaviour of the composite microstructure has been reported for two arrangements of the cylinders in skin and core layers. The behaviour is very different to that observed either for uniaxially oriented or isotropic samples. Deformation is far from being affine. Cylinders aligned in the direction of stretch show fragmentation, but complete recovery of the spacing between cylinders on removal of the load. Those oriented perpendicular to the direction of stretch incline at an angle of approximately 25° to their original direction during load.

A global sensitivity analysis approach applied to a multiscale model of microvascular flow.

A global sensitivity analysis of a multiscale computational model of microvascular flow is presented. A total of 140 simulations have been completed and analyzed varying 6 input parameters and considering their effects on 7 output variables. Interestingly, the vascular network topology has been found as a determinant factor for both vasculature-related and interstitium-related quantities. Regarding the firsts, the vascular network topology has obtained a score of 5.5/6 and 6/6 for average and spatial distribution respectively (where 6 is the maximum and 1 is the minimum). On the other hand, considering interstitium-related quantities, the score is 4/6 and 5/6 for average and spatial distribution respectively. These results suggest that the network topology has a significant influence on the outcome of the computational analysis.

Inflammatory response to magnesium-based biodegradable implant materials.

Biodegradability and mechanical properties of magnesium alloys are attractive for orthopaedic and cardiovascular applications. In order to study their cytotoxicity usually bone cells are used. However, after implantation, diverse and versatile cells are recruited and interact. Among the first ones coming into play are cells of the immune system, which are responsible for the inflammatory reaction. Macrophages play a central role in the inflammatory process due to the production of cytokines involved in the tissue healing but also in the possible failure of the implants. In order to evaluate the in vitro influence of the degradation products of magnesium-based alloys on cytokine release, the extracts of pure magnesium and two magnesium alloys (with gadolinium and silver as alloying elements) were examined in an inflammatory in vitro model. Human promonocytic cells (U937 cells) were differentiated into macrophages and further cultured with magnesium-based extracts for 1 and 3 days (simulating early and late inflammatory reaction phases), either at 37 °C or at 39 °C (mimicking normal and inflammatory conditions, respectively). All extracts exhibit very good cytocompatibility on differentiated macrophages. Results suggest that M1 and even more M2 profiles of macrophage were stimulated by the extracts of Mg. Furthermore, Mg-10Gd and Mg-2Ag extracts introduced a nuancing effect by rather inhibiting macrophage M1 profile. Magnesium-based biomaterials could thus induce a faster inflammation resolution while improving tissue repair. STATEMENT OF SIGNIFICANCE: Macrophage are the key-cells during inflammation and can influence the fate of tissue healing and implant performance. Magnesium-based implants are biodegradable and bioactive. Here we selected an in vitro system to model early and late inflammation and effect of pyrexia (37 °C versus 39 °C). We showed the beneficial and nuancing effects of magnesium (Mg) and the selected alloying elements (silver (Ag) and gadolinium (Gd)) on the macrophage polarisation. Mg extracts exacerbated simultaneously the macrophage M1 and M2 profiles while Mg-2Ag and Mg-10Gd rather inhibited the M1 differentiation. Furthermore, 39 °C exhibited protective effect by either decreasing cytokine production or promoting anti-inflammatory ones, with or without extracts. Mg-based biomaterials could thus induce a faster inflammation resolution while improving tissue repair.

A prospective Italian survey on the safety of subcutaneous immunotherapy for respiratory allergy.

BACKGROUND: Subcutaneous immunotherapy is effective for the treatment of respiratory allergy, and it is largely used in Italy, but no systematic safety assessment has been carried out so far. OBJECTIVE: To assess prospectively the safety of injection immunotherapy in a multicentre, real-life survey. METHODS: Eleven Italian allergy departments recorded the clinical characteristics of systemic reactions (SRs) due to immunotherapy. Vaccines were prescribed according to guidelines; only standardized depot extracts were used. SRs were graded according to the EAACI recommendations, and were classified as immediate or delayed. RESULTS: One thousand seven hundred and thirty-eight patients (847 males, age range 5-71) received immunotherapy from eight different manufacturers, for a total of 2038 courses (300 patients received two extracts). A total of 60 785 injections were given over a mean immunotherapy duration of 3 years. Overall, 95 reactions were observed in 57 patients (3.28%), corresponding to 4.7% of the courses and 1.56/1000 injections. Twenty-five patients experienced more than one adverse event. There were 34 grade 2, 60 grade 3 and one grade 4 reactions and no fatality. SRs occurred more frequently in patients with asthma than in patients with rhinitis alone (4.1% vs. 1.1%), and were equally distributed between the build-up and the maintenance phase. Ragweed and grass extracts caused significantly more side effects than other allergens. CONCLUSION: In this large prospective study, the rate of SRs was low, thus confirming that injection immunotherapy has an acceptable risk/benefit ratio when prescribed and carried out according to recommendations.

Possible antioxidant role of SPA therapy with chlorine-sulphur-bicarbonate mineral water.

The aim of our research was to analyze the antioxidant role and efficacy of thermal or salus per aquam (spa) therapy with chlorine-sulphur-bicarbonate mineral water. The study has been performed on 30 rats. The animals were randomized in three groups, each of them composed by ten animals, denominated A, B and C. The A group was the control group and was not subjected to any specific treatment (placebo); the B group has been treated with a standard cycle of hydropinics treatment with mineral water of Therme of Stabia in Castellammare (Naples, Italy) denominated STABIA; the C group was treated with a standard cycle of hydropinic treatment with mineral water of Therme of Stabia in Castellammare (Naples, Italy) denominated SULFUREA. After two weeks of treatment all the rats were sacrificed and blood was collected for the plasmatic determination of reactive oxygen species (ROS). The results demonstrated a significant (P < 0.05) reduction of ROS in B (374 Carr. U. +/-73) and C group (399 carr. U. +/-62) treated with mineral waters if compared with control group (571 + 69 Carr. U.). In conclusion this study suggests a possible antioxidant effect of chlorine-sulphur-bicarbonate spa hydropinic treatment with a consequent suitable intestinal physiology, with reduction of the functional and organic modifications that can lead to pathological disorders of the gastroenteric diseases in whose pathogenesis the oxidative stress can develop an important role.

Matrices based on lineal and star fumarate-metha/acrylate copolymers for bone tissue engineering: Characterization and biocompatibility studies.

This article presents the preparation of matrices from two new families of fumaric copolymers and the effect of structural differences on their physicochemical and biological behavior. Diisopropyl fumarate (DIPF) and poly(ethylene glycol) methyl ether methacrylate (OEGMA) or N-isopropylacrylamide (NIPAM) were copolymerized by conventional radical and RAFT polymerization to obtain lineal or start architectures, respectively. These copolymers were characterized by spectroscopic (FTIR and 1 H-NMR) and chromatographic methods. The thermal stability was studied by thermal gravimetric analysis, showing some differences in relation to the architecture and chemical nature of copolymers. SEM morphological analysis demonstrated that the surface of the matrices derived from OEGMA exhibited an irregular and rough surface, while DIPF-NIPAM copolymers presented smooth surface with nearly no significant porosity. The matrix obtained of both kinds of copolymers presented no cytotoxicity as it was evaluated using a model of macrophages on culture. Moreover, cell growth was better on the surfaces of the DIPF-NIPAM matrices, suggesting a good interaction with this matrix and its potential application as matrices for tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 195-203, 2019.

Model of arterial tree and peripheral control for the study of physiological and assisted circulation.

Peripheral vasomotion, interstitial liquid exchange, and cardiovascular system behaviour are investigated by means of a lumped parameter model of the systemic and peripheral circulation, from the aortic valve to the venules. This modelling work aims at combining arterial tree hemodynamics description, active peripheral flow regulation, and fluid exchange. The arterial compartment is constructed with 63 RCL segments and 30 peripheral districts including myogenic control on arterioles, metabolic control on venules, and Starling filtration through capillary membrane. The arterial behaviour is characterised as to the long term stability of pressure/flow waves in the different segments. Peripheral districts show autoregulatory capabilities against pressure changes over a wide range and also self-sustained oscillations mimicking vasomotor activity. A preliminary study was carried out as to the model response to changes induced by cardiopulmonary bypass (CPB). Among the induced alterations, the system responds mainly to hemodilution, which increased peripheral fluid loss and oedema beyond the compensatory capabilities of local regulation mechanisms. This resulted in an overall increase total arterial resistance. Local transport deficits were assessed for each district according to the different metabolic demand. This study shows the requirement of a suitable description of both arteries and peripheral mechanisms in order to describe cardiovascular response non-physiological conditions, as well as assisted circulation or other pathological conditions.

A new method to evaluate patient characteristic response to ultrafiltration during hemodialysis.

BACKGROUND: Several factors are involved in the pathogenesis of dialysis discomfort interfering with optimal fluid removal and reducing the efficacy of the treatment; the most important one is a decrease in blood volume caused by an imbalance between ultrafiltration (UF) and plasmarefilling (PR) rates. OBJECTIVES: This study is aimed at devising a method to tailor the dialysis therapy to each individual patient, by analyzing the relationship between PR and UF during the sessions in stable patients and widening the knowledge of fluid exchanges during the treatment. METHODS: Thirty stable patients undergoing maintenance hemodialysis were enrolled. Three dialysis sessions were monitored for each patient; systemic pressure, blood composition, blood volume % variation, weight loss and conductivity were recorded repeatedly. A Plasma Refilling Index (PRI), defined and calculated by means of parameters measured throughout the dialysis, was introduced as a novel instrument to study plasma refilling phenomena. Results. The PRI provides understanding of patient response (in terms of plasma refilling) to the set UF. In the monitored sessions, the PRI trend is found to be characteristic of each patient; a PRI course that is at variance with the characteristic trend is a signal of inadequate or unusual dialysis scheduling. Moreover, statistical analysis highlights two different PRI trends during the first hour and during the rest of the treatment, suggesting the presence of different treatment phases. CONCLUSION: The main advantage of the PRI index is that it is non-invasive peculiar to each patient and easy to compute in a dialysis routine based on online data recorded by the monitor. A deviation from the characteristic trend may be a warning for the clinician. The analysis of the PRI trend also suggests how to modulate UF as a function of interstitial to intravascular fluid removal balance during dialysis.

[Sulphurous vaginal douching and vulvovaginal atrophy].

OBJECTIVE: During climacteric the reduction or interruption of estrogenic stimulus determines a gradual atrophy of the tissues of the urogenital tract.Vulvovaginal atrophy can be cause of dryness, itch, burning, and dyspareunia. Vulvovaginal atrophy is associated also with depression. Hence the importance of an appropriate treatment of the vulvovaginal atrophy. Between therapeutic options we can add, particularly for women who suffer only from vaginal symptoms, the spa therapy that uses mineral waters with benefic effects on vaginal tissue wellness and health. On the basis of considerations described above and on the insufficient literature data, the objective of our single-arm pilot study has been to evaluate, in women suffering from vulvovaginal atrophy, the effects and safety of a vaginal douching cycle with sulphurous mineral water and impact on depression disorder frequently observed. PATIENTS AND METHODS: The study was conducted on 24 women affected by vulvovaginal atrophy; mean age:57±11 years; age range:42-81 years. The subjects were treated, for 2 weeks, with sulphurous vaginal douching from Terme of Telese S.p.A. (Benevento-Italy). At the beginning and at the end of the SPA treatment the following symptoms were evaluated: dryness, burning, itch, dyspareunia and leucorrhoea (using VAS scale); the impact on psychological distress (using S.D.S. Zung-test). RESULT: At the end of the spa treatment, the mean values±SD, compared to baseline, have showed a significant (p<0.05) reduction in leucorrhoea (-88%), in vulvar itch (-79%), in vaginal burning (-71%), in vaginal dryness (-65%) with an improvement of psichological distress as demonstrated by S.D.S. Zung-test. CONCLUSION: The data of this single-arm pilot clinical trial show that the sulphurous vaginal douching cycle can be considered very useful in women suffering from vulvovaginal atrophy with improving of the quality of life and social relationship.

[Sulphur mud-bath treatment in osteoarthrosis: therapeutic activity and efficiency on the quality of life]. / La fangobalneoterapia sulfurea nell'osteoartrosi: attività tera- peutica ed efficacia sulla qualità di vita.

OBJECTIVES: Osteoarthrosis (OA) is a degenerative condition of the joints, involving: cartilage, synovia and bone. The onset is gradual with articular pain, functional difficulties, articular rigidity being accompanied by depression. Spa therapy with mud-bath treatment (FBT) is a promising management practice that can improve the quality of life for these patients. Few studies have investigated the impact of the FBT on the quality of life for patients with OA. The aim of our study was to investigate the "short-term" therapeutic effects and the impact on the quality of life using sulphur FBT in OA. PATIENTS AND METHODS: The study has been performed on 51 subjects affected by OA, being 32 (63%) women and 19 (37%) males (mean age: 62 +/- 1,2 years, age range: 44-77 years). The investigated subjects underwent 12 consecutive days sulphur mud-bath treatment (FBT) from Terme of Telese in Telese Terme (Benevento-Italy). At the beginning and at the end of the Spa therapy the clinical symptoms induced by OA and the impact of sulphur FBT treatment on quality of life were measured using VAS scale, WOMAC and SF-36 questionnaires. RESULTS: At the end of Spa therapy the results of our study, showed a significant (P < 0.05) reduction of the symptoms and improved quality of life. CONCLUSIONS: The data of this first series of investigations suggests that sulphur FBT is useful in improving the quality of life of patients with OA.

Effectiveness of sulphur spa therapy with politzer in the treatment of rhinogenic deafness.

Several studies have focused on the usefulness of sulphur, radioactive and bromo-iodine mineral waters in the treatment of chronic inflammatory lower and upper respiratory processes. The purpose of this study was to evaluate the tolerability, effectiveness and impact on quality of life of sulphur spa therapy with Politzer in subjects with chronic inflammatory processes responsible for the onset or persistence of rhinogenic deafness. The study was performed on 27 subjects (mean age 62 +/- 2.2 years, range: 28-88) with chronic catarrhalis otitis, chronic rhino-sinusitis and pharyngeal inflammation. These patients underwent 12 sessions of humid-hot inhalation, with vapour jet 20 cm from the face, at 38 degrees C for 10 min, followed by Politzer with sulphur sodium chloride bicarbonate alkaline mineral water from "Rosapepe" Spa, in Contursi (Salerno, Italy). Middle ear function and possible social recovery (based on Giaccai and Gardenghi guidelines) of the patients were assessed, at the beginning and end of the spa therapy. Results, at the end of this treatment, showed a significant (p < 0.05) increase in audiometric curves corresponding to the normal ventilation of the tympanic box (incidence of 24% before therapy and 33% thereafter) and a decrease in pathological curves. Moreover, a significant (p < 0.05) reduction in the percentage of auditory loss was recorded (N = 41; 19.7% +/- 2.5 --> 13.9% +/- 1.9) and improved hearing, at the frequencies required for daily activities: 500-1000 and 2000 Hz (31.1 dB +/- 1.7 --> 26.8 dB +/- 1.5). No adverse effects to the spa therapy were observed during the study. In conclusion, the results of this study are in agreement with data in the literature, demonstrating that associated spa therapy with Politzer and inhalation have a positive impact on the therapeutic strategy of chronic inflammatory processes, responsible for the onset or persistence of rhinogenic deafness, in order to enhance and combine with the already consolidated pharmacological approaches.

Resolution of subchorionic hematoma and symptoms of threatened miscarriage using vaginal alpha lipoic acid or progesterone: clinical evidences.

OBJECTIVE: Alpha Lipoic Acid (ALA) is a safe natural molecule that exerts a selective immunomodulating activity with antioxidant and anti-inflammatory properties. This randomized controlled clinical trial (RCT) tested the effect of the vaginal administration with ALA or Progesterone, in subchorionic hematoma resorption in women with threatened miscarriage. PATIENTS AND METHODS: 400 mg of vaginal Progesterone or 10 mg of vaginal ALA were administered to sixty-two pregnant women, in the first trimester of gestation with threatened miscarriage and subchorionic hematoma. Controls were patients who chose not to receive any treatment. RESULTS: In the ALA group the subchorionic hematoma was reabsorbed more quickly in comparison with the progression detected in Progesterone group (p ≤ 0.05). The other parameters checked (pelvic pain and vaginal bleeding) did not show any significant difference and a smaller number of miscarriages was recorded in the ALA group, compared to Progesterone group. CONCLUSIONS: Our data provides the first evidence of the efficacy of ALA, administered by vaginal route, in the healing process of patients with threatened miscarriage, thus supporting the normal course of pregnancy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02601898 (ClinicalTrials.gov registry).

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice.

The administration of mineral sulphur water is an alternative experimental approach for the treatment of rheumatic diseases, such as osteoarthritis (OA), that cause the degeneration of bone and cartilage and sufferance to the patients. Chondroitin sulfate (CS) is a symptomatic slow acting nutropeucital agent currently used in molecular therapy of OA. Therefore, we have studied the role and efficacy of the selective soil paste from the mineral sulphur enriched spring (mud)-therapy alone or in combination with CS in the treatment of OA. The study was performed on 40 C57 Black 6N mice, an experimental model which spontaneously develop an osteoarthritic process. The animals were divided in 4 groups and were treated with the single agents or with the combination. After 30 days of treatment all the mice were sacrificed and right knees and blood were collected. It was found that CS determined a reduction of radiological and histological features of chondrodegeneration and that mud-therapy increased the effects of CS in the animal group treated with the combination. However, the effects of thermal therapy alone were not statistically significant. Since OA is characterized by an increase of the production of nitric oxide (NO) by chondrocytes in extracellular matrix with its consequent elevation in serum and synovial fluid, we have evaluated the effects of the treatments on serum NO levels. CS alone induced a statistically significant reduction of NO serum levels (90+/-13 micromM vs 219+/-60 microM of control group, P<0.05) while mud-therapy alone induced a not statistically significant reduction of serum NO (170+/-62 microM, P>0.05). However, the latter strongly potentiated the decrease of serum NO induced by CS (31+/-1.5 microM) with a high statistical significance if compared to both the control group (P<0.01) and the CS-treated group (P<0.05). In conclusion, this study demonstrates that mud-therapy with sulphur mineral water could represent an important phase of the therapeutic strategy of OA. This experimental strategy could integrate and potentiate the standard pharmacological tools. Moreover, we have set a valid experimental in vivo model for the study of the thermal effects on the development of OA.

A mechanical model lung for hydraulic testing of total liquid ventilation circuits.

A new model lung (ML), designed to reproduce the tracheal pressure vs. fluid flow relationship in animals undergoing total liquid ventilation (TLV) trials, was developed to be used as a mock bench test for neonatal TLV circuits. The ML is based on a linear inertance-resistance-compliance (LRC) lumped-parameter model of the respiratory system with different resistance values for inspiration (R insp ) or expiration (R exp ). The resistant element was set up using polypropylene hollow fibres packed inside a tube. A passive one-way valve was used to control the resistance cross-section area provided for the liquid to generate different values for R insp or R exp , each adjustable by regulating the active length of the respective fibre pack. The compliant element consists of a cylindrical column reservoir, in which bars of different diameter were inserted to adjust compliance (C). The inertial phenomena occurring in the central airways during TLV were reproduced by specifically dimensioned conduits into which the endotracheal tube connecting the TLV circuit to the ML was inserted. A number of elements with different inertances (L) were used to simulate different sized airways. A linear pressure drop-to-flow rate relationship was obtained for flow rates up to 5 l/min. The measured C (0.8 to 1.3 mL cmH2O (-1) kg(-1)), R insp (90 to 850 cmH2O s l(-1)), and R exp (50 to 400 cmH2O s l(-1)) were in agreement with the literature concerning animals weighing from 1 to 12 kg. Moreover, features observed in data acquired during in vivo TLV sessions, such as pressure oscillations due to fluid inertia in the upper airways, were similarly obtained in vitro thanks to the inertial element in the ML.