Drug-Induced Sleep Endoscopy (DISE) with Simulation Bite to Predict the Success of Oral Appliance Therapy in Treating Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS).

STUDY OBJECTIVES: Oral appliances have gained their place in the treatment of obstructive sleep apnea (OSA) where custom-made titratable mandibular advancement devices (MAD) have become the oral appliance of choice. This study aimed to asses the value of the drug-induced sleep endoscopy (DISE) using a MAD in the prediction of treatment outcome for OSAHS. METHODS: This is a prospective, single-center cohort study that enrolled sixty-six consecutive patients with diagnosed OSA (5 events/h < apnea-hypopnea index (AHI) < 50 events/h) to be treated with a custom-made titratable MAD. The patients were evaluated polysomnographically with the MAD in situ after the adaptation and titration period of 3 months. The associations between findings during DISE and treatment outcome were assessed. RESULTS: The subjects showed a wide range of severity of OSAHS pre-treatment: median AHI was 43.10 with a range from 20.13 to 66.07. The simulation bite was associated with a significant increase in cross-sectional area at level of the velopharynx, tongue base and epiglottis. MAD treatment response in the studied population was 91%, with a mean AHI improving from 43.10 to 12.93. CONCLUSIONS: Drug-induced sleep endoscopy with simulation bite is an acceptably reproducible technique for determining the sites of obstruction in OSAHS subjects; it thus offers possibilities as a prognostic indicator for treatment with MAD.

Time Dependence of the Electron and Positron Components of the Cosmic Radiation Measured by the PAMELA Experiment between July 2006 and December 2015.

Cosmic-ray electrons and positrons are a unique probe of the propagation of cosmic rays as well as of the nature and distribution of particle sources in our Galaxy. Recent measurements of these particles are challenging our basic understanding of the mechanisms of production, acceleration, and propagation of cosmic rays. Particularly striking are the differences between the low energy results collected by the space-borne PAMELA and AMS-02 experiments and older measurements pointing to sign-charge dependence of the solar modulation of cosmic-ray spectra. The PAMELA experiment has been measuring the time variation of the positron and electron intensity at Earth from July 2006 to December 2015 covering the period for the minimum of solar cycle 23 (2006-2009) until the middle of the maximum of solar cycle 24, through the polarity reversal of the heliospheric magnetic field which took place between 2013 and 2014. The positron to electron ratio measured in this time period clearly shows a sign-charge dependence of the solar modulation introduced by particle drifts. These results provide the first clear and continuous observation of how drift effects on solar modulation have unfolded with time from solar minimum to solar maximum and their dependence on the particle rigidity and the cyclic polarity of the solar magnetic field.

New upper limit on strange quark matter abundance in cosmic rays with the PAMELA space experiment.

In this work we present results of a direct search for strange quark matter (SQM) in cosmic rays with the PAMELA space spectrometer. If this state of matter exists it may be present in cosmic rays as particles, called strangelets, having a high density and an anomalously high mass-to-charge (A/Z) ratio. A direct search in space is complementary to those from ground-based spectrometers. Furthermore, it has the advantage of being potentially capable of directly identifying these particles, without any assumption on their interaction model with Earth's atmosphere and the long-term stability in terrestrial and lunar rocks. In the rigidity range from 1.0 to ∼1.0×10^{3} GV, no such particles were found in the data collected by PAMELA between 2006 and 2009. An upper limit on the strangelet flux in cosmic rays was therefore set for particles with charge 1≤Z≤8 and mass 4≤A≤1.2×10^{5}. This limit as a function of mass and as a function of magnetic rigidity allows us to constrain models of SQM production and propagation in the Galaxy.

Dietary fatty acids affect mitochondrial phospholipid compositions and mitochondrial gene expression of rainbow trout liver at different ages.

Mitochondria are among the first responders to various stressors that challenge the homeostasis of cells and organisms. Mitochondrial decay is generally associated with impairment in the organelle bioenergetics function and increased oxidative stress, and it appears that deterioration of mitochondrial inner membrane phospholipids (PL), particularly cardiolipin (CL), and accumulation of mitochondrial DNA (mtDNA) mutations are among the main mechanisms involved in this process. In the present study, liver mitochondrial membrane PL compositions, lipid peroxidation, and mtDNA gene expression were analyzed in rainbow trout fed three diets with the same base formulation but with lipid supplied either by fish oil (FO), rapeseed oil (RO), or high DHA oil (DHA) during 6 weeks. Specifically, two feeding trials were performed using fish from the same population of two ages (1 and 3 years), and PL class compositions of liver mitochondria, fatty acid composition of individual PL classes, TBARS content, and mtDNA expression were determined. Dietary fatty acid composition strongly affected mitochondrial membrane composition from trout liver but observed changes did not fully reflect the diet, particularly when it contained high DHA. The changes were PL specific, CL being particularly resistant to changes in DHA. Some significant differences observed in expression of mtDNA with diet may suggest long-term dietary effects in mitochondrial gene expression which could affect electron transport chain function. All the changes were influenced by fish age, which could be related to the different growth rates observed between 1- and 3-year-old trout but that could also indicate age-related changes in the ability to maintain structural homeostasis of mitochondrial membranes.

Perisurgical and intra-rehabilitative salivary steroid hormone profiles in bicompartmental arthroplasty.

Sex hormones play a role in pain perception, a key variable in evaluating the progression and treatment of osteoarthritis. The aim of this study was to determine the relationship between salivary concentrations of four steroid hormones and functional/clinical outcomes after hip and knee arthroplasty. Saliva samples were collected from 24 otherwise healthy patients with osteoarthritis before surgery, on admission to rehabilitation, and at hospital discharge. Salivary concentrations of testosterone, 17ß-estradiol, dehydroepiandrosterone (DHEA), and cortisol were immunoassayed. Changes in hormone levels were compared with clinical outcomes, as assessed by functional independence measure (FIM®), Barthel Index (BI), and visual analog scale for pain (VAS) scores. Changes in testosterone levels were significantly inversely correlated with VAS (r= -0.53, p=0.043) and FIM® and BI scores in all patients (r= -0.30, p= 0.043, and r= -0.35, p=0.031, respectively). The testosterone to cortisol ratio was inversely correlated with BI scores in all patients (r= -0.30, p=0.040), and in the men (r= -0.55, p=0.005) and the women (r= -0.28, p=0.042) when analyzed separately. Changes in salivary testosterone concentrations closely correlated with clinical outcome measurements for total hip and knee arthroplasty. Clinical outcome after arthroplasty was generally better among the men.

Cosmic-ray positron energy spectrum measured by PAMELA.

Precision measurements of the positron component in the cosmic radiation provide important information about the propagation of cosmic rays and the nature of particle sources in our Galaxy. The satellite-borne experiment PAMELA has been used to make a new measurement of the cosmic-ray positron flux and fraction that extends previously published measurements up to 300 GeV in kinetic energy. The combined measurements of the cosmic-ray positron energy spectrum and fraction provide a unique tool to constrain interpretation models. During the recent solar minimum activity period from July 2006 to December 2009, approximately 24,500 positrons were observed. The results cannot be easily reconciled with purely secondary production, and additional sources of either astrophysical or exotic origin may be required.

The gene expression response of the catadromous perciform barramundi Lates calcarifer to an acute heat stress.

The acute heat-shock response of the tropical estuarine fish species barramundi Lates calcarifer as indicated by the expression of genes within stress (hsp 90AA, hsp 90AB, hsp 70 and hsc 70), metabolic (cisy, cco II and ldh) and growth (igf1 and mstn 1) related pathways was examined following an increase in water temperature from 28 to 36° C over 30 min. Lates calcarifer were maintained at the acute stress temperature of 36° C for 1 h before being returned to 28° C and allowed to recover at this temperature for a further 2 weeks. Muscle tissue sampling over the experimental period allowed for the expression quantification of stress, metabolic and growth-related genes via quantitative real-time polymerase chain reaction (qrt-PCR) where a robust and reliable normalization approach identified both α-tub and Rpl8 as appropriate genes for the analysis of gene expression in response to an acute heat stress. hsp90AA and hsp70 of the inducible heat-shock response pathway showed a massive up-regulation of gene expression in response to heat stress, whilst the constitutive heat-shock genes hsp90AB and hsp70 showed no change over the course of the experiment and a small increase after 2 weeks of recovery, respectively. Of the three genes representing the metabolic pathway (cisy, cco II and ldh) only cco II changed significantly showing a decrease in gene expression, which may suggest a small suppression of aerobic metabolism. igf1 of the growth pathway showed no significant differences in response to an acute heat stress, whilst mstn1 increased at the beginning of the heat stress but returned to basal levels soon after. Overall, the results demonstrate that an acute heat stress in L. calcarifer caused a significant increase in the expression of genes from the stress response pathway and a possible decrease in aerobic metabolism with only relatively minor changes to the growth pathway highlighting the hardy nature of L. calcarifer and its resilience in coping with sudden temperature changes routinely encountered within its natural environment.

Treatment of horizontal canal benign paroxysmal positional vertigo: a new rehabilitation technique.

The aim of this study was to evaluate the effectiveness of a new technical variant applied to the Gufoni's manoeuvre, in the treatment of horizontal canal benign paroxysmal positional vertigo (HSC-BPPV). 87 patients with BPPV of HSC (55 women and 32 men), aged between 21 and 80 years, were randomized either to modified Gufoni's manoeuvre or to the Gufoni's manoeuvre. 93% of patients treated with modified Gufoni's manoeuvre was cured after the first treatment session, of which only 2% had a conversion into PSC-BPPV, while the Gufoni's manoeuvre led to a symptoms resolution in 88% of cases, of which 16% had a conversion into PSC-BPPV. Therefore, the modified Gufoni's manoeuvre shows the same effectiveness in the resolution of symptoms of Gufoni's manoeuvre, but it appears more effective than the latter to reduce the percentage of conversion of the HSC-BPPV into PSC-BPPV (χ(2) = 6.13, P = 0.047).

Cosmic-ray electron flux measured by the PAMELA experiment between 1 and 625 GeV.

Precision measurements of the electron component in the cosmic radiation provide important information about the origin and propagation of cosmic rays in the Galaxy. Here we present new results regarding negatively charged electrons between 1 and 625 GeV performed by the satellite-borne experiment PAMELA. This is the first time that cosmic-ray e⁻ have been identified above 50 GeV. The electron spectrum can be described with a single power-law energy dependence with spectral index -3.18 ± 0.05 above the energy region influenced by the solar wind (> 30 GeV). No significant spectral features are observed and the data can be interpreted in terms of conventional diffusive propagation models. However, the data are also consistent with models including new cosmic-ray sources that could explain the rise in the positron fraction.

Heavy-ion anisotropy measured by ALTEA in the International Space Station.

The uneven shielding of the International Space Station from the vessel hull, racks and experiments produces a modulation of the internal radiation environment. A detailed knowledge of this environment, and therefore of the Station's shielding effectiveness, is mandatory for an accurate assessment of radiation risk. We present here the first 3D measurements of the Station's radiation environment, discriminating particle trajectories and LET, made possible using the detection capability of the ALTEA-space detector. We provide evidence for a strong (factor ≈ 3) anisotropy in the inner integral LET for high-LET particles (LET > 50 keV/µm) showing a minimum along the longitudinal station axis (most shielded) and a maximum normal to it. Integrating over all measured LETs, the anisotropy is strongly reduced, showing that unstopped light ions plus the fragments produced by heavier ions approximately maintain flux/LET isotropy. This suggests that, while changing the quality of radiation, the extra shielding along the station main axis is not producing a benefit in terms of total LET. These features should be taken into account (1) when measuring radiation with detectors that cannot distinguish the direction of the impinging radiation or that are unidirectional, (2) when planning radiation biology experiments on the ISS, and (3) when simulating the space radiation environment for experiments on the ground. A novel analysis technique that fully exploits the ability to retrieve the angular distribution of the radiation is also presented as well as the angular particle flux and LET characteristic of three geomagnetic zones measured during 2009 by the ALTEA-space detector. This technique is applied to the ALTEA-space detector, but a wider applicability to other detectors is suggested.

PAMELA measurements of cosmic-ray proton and helium spectra.

Protons and helium nuclei are the most abundant components of the cosmic radiation. Precise measurements of their fluxes are needed to understand the acceleration and subsequent propagation of cosmic rays in our Galaxy. We report precision measurements of the proton and helium spectra in the rigidity range 1 gigavolt to 1.2 teravolts performed by the satellite-borne experiment PAMELA (payload for antimatter matter exploration and light-nuclei astrophysics). We find that the spectral shapes of these two species are different and cannot be described well by a single power law. These data challenge the current paradigm of cosmic-ray acceleration in supernova remnants followed by diffusive propagation in the Galaxy. More complex processes of acceleration and propagation of cosmic rays are required to explain the spectral structures observed in our data.

Differential tissue-regulation of myostatin genes in the teleost fish Lates calcarifer in response to fasting. Evidence for functional differentiation.

Gene or genome duplication is a fundamental evolutionary mechanism leading towards the origin of new genes, or gene functions. Myostatin (MSTN) is a negative regulator of muscle growth that in teleost fish, as a result of genome duplication, is present in double copy. This study provides evidence of differentiation of MSTN paralogs in fish by comparatively exploring their tissue-regulation in the Asian sea bass (Lates calcarifer) when subjected to fasting stress. Results showed differential regulation as well as specific tissue-responses in the muscle, liver, gill and brain of L. calcarifer after nutritional deprivation. In particular, the LcMstn-1 expression increased in liver (∼4 fold) and muscle (∼3 fold) and diminished in brain (∼0.5 fold) and gill (∼0.5 fold) while that of LcMstn-2 remained stable in brain and muscle and was up regulated in gill (∼2.5 fold) and liver (∼2 fold). Differential regulation of Mstn paralogs was supported by in silico analyses of regulatory motifs that revealed, at least in the immediate region upstream the genes, a differentiation between Mstn-1 and Mstn-2. The Mstn-1 in particular showed a significantly higher conservation of regulatory sites among teleost species compared to its paralog indicating that this gene might have a highly conserved function in the taxon.

PAMELA results on the cosmic-ray antiproton flux from 60 MeV to 180 GeV in kinetic energy.

The satellite-borne experiment PAMELA has been used to make a new measurement of the cosmic-ray antiproton flux and the antiproton-to-proton flux ratio which extends previously published measurements down to 60 MeV and up to 180 GeV in kinetic energy. During 850 days of data acquisition approximately 1500 antiprotons were observed. The measurements are consistent with purely secondary production of antiprotons in the Galaxy. More precise secondary production models are required for a complete interpretation of the results.

Enhancement of the HIV-1 inhibitory activity of RANTES by modification of the N-terminal region: dissociation from CCR5 activation.

Although selected chemokines act as natural inhibitors of human immunodeficiency virus (HIV) infection, their inherent proinflammatory activity may limit a therapeutic use. To elucidate whether the antiviral and signaling functions of RANTES can be dissociated, several recombinant analogues mutated at the N terminus were generated and functionally compared with the wild-type (WT) molecule, as well as with three previously described mutants. Substitution of selected residues within the N-terminal region caused a marked loss of antiviral potency. By contrast, two unique analogues (C1.C5-RANTES and L-RANTES) exhibited an increased antiviral activity against different CXCR4-negative HIV-1 isolates grown in primary mononuclear cells or in macrophages. This enhanced HIV-blocking activity was associated with an increased binding affinity for CCR5. Both C1.C5-RANTES and L-RANTES showed a dramatically reduced ability to trigger intracellular calcium mobilization via CCR3 or CCR5, while potently antagonizing the action of the WT chemokine. By contrast, two previously described analogues (RANTES(3-68) and AOP-RANTES) maintained a WT ability to trigger CCR5-mediated signaling, while a third one (RANTES(9-68)) showed a dramatic loss of antiviral activity. These data demonstrate that the antiviral and signaling functions of RANTES can be uncoupled, opening new perspectives for the development of chemokine-based therapeutic approaches for HIV infection.

Early production of HIV-1 neutralising antibodies in patients following highly active antiretroviral treatment (HAART) during primary HIV infection.

We investigate the effects of highly active antiretroviral therapy (HAART) on humoral immune responses during a 24-month follow up of 15 HIV patients with acute primary HIV infection. The patients were divided into three groups on the basis of the therapeutic protocol they were following at the time of entry: a) five naive patients (untreated or treated with only ZDV or AZT); b) five patients following a triple combination of ZDV+ lamivudine (3TC)+ saquinovir (SQV); and c) five patients on a four-drug combination of ZDV+3TC+SQV+ ritonavir (RTV). The results show that the early introduction of HAART greatly reduces plasma viremia levels and restores the number of CD4 cells. A significant correlation was found between anti HIV neutralising activity and the four-drug, but not the three-drug combination. The reduction in infectivity was directed against viruses of different clades and associated with immunoglobulin fractions. Moreover, the neutralising antibodies in the HAART-treated patients appeared after two weeks of treatment and remained stable throughout the 24 months of follow up. The early appearance of neutralising antibodies represent an important component of immune responses during primary HIV infection, may contribute towards immune reconstitution in patients on HAART, and give further information that may be useful in developing new strategies designed to eradicate the disease.

Penile metastasis from carcinoma of the prostate in a patient with high serum prostate specific antigen levels.

Prostatic carcinoma metastasizing to the penis is rare. Prognosis is poor with survival ranging from 1 to 24 months. A patient with prostate cancer and a serum Prostate Specific Antigen (PSA) level over 200 ng/ml, submitted to radical retropubic prostatectomy (RRP) and after 2 months presenting with two painful nodules in the penis, is described.

[Response of interleukin-6 in patients undergoing a laparoscopic or laparotomic cholecystectomy]. / Risposta della interleukina-6 in pazienti sottoposti a colecistectomia laparoscopica o laparotomica.

BACKGROUND: It is well known that surgery induces an acute inflammatory response associated with significant increase of interleukin-6 (IL-6) and C reactive protein (CRP). Laparoscopic cholecystectomy (LC) is a so called "mini-invasive" surgical intervention and on the basis of this consideration it has been investigated if and how serological markers of inflammation are modified in patients after laparoscopic cholecystectomy compared to patients undergoing open cholecystectomy. METHODS: The acute phase of inflammation (IL-6, CRP and body temperature) was evaluated in 53 patients one day before surgery and p.o. after 1, 3 and 6 days; 26 patients underwent "open" cholecystectomy and 27 LC. RESULTS: One day after surgery patients with open cholecystectomy showed significant increase (p < 0.05) of IL-6, CRP and body temperature, while these parameters were almost unchanged in patients with LC. In patients with "open" cholecystectomy, 2 p.o. complications (pneumonia) were observed. CONCLUSIONS: In conclusion, LC, although it requires longer operative time, strongly reduces p.o. pain, hospitalization, promotes earlier recovery and return to normal activity, avoiding the acute phase of p.o. inflammation with better p.o. morbidity compared to open surgery.

[The use of prosthetic meshes in the surgical treatment of inguinal hernia: the costs and profits for the local health screening unit]. / Utilizzazione delle reti protesiche nel trattamento chirurgico dell'ernia inguinale: costi e guadagni per la ULSS.

BACKGROUND: Inguinal hernioplasty represents one of the most frequently performed surgical operation. The recent introduction of prosthetic mesh made Bassini operation obsolete, with more space gained by the newly developed "tension-free" and "sutureless" surgical techniques. This new approach, however, results in increased initial costs for the hospital, due to the purchase of mesh materials. On the other hand a reduction of overall expenses for a single hernia repair should be expected. In this work an attempt is made to verify this, by calculating the cost-benefit ratio of different techniques for hernia repair. METHODS: The type and amount of materials used in a standard Bassini hernia repair, Lichtenstein and Trabucco have been examined. The amount of anesthetic drugs required, the average hospital stay and time away from work were recorded too. The costs of the three operations considered, not including routine expenses (operating room, bed sheet, etc.) have been estimated. RESULTS: Lichtenstein and Trabucco repair performed in local anesthesia (L. 1.354.120, L. 1.567.120) were cheaper than Bassini (L. 2.820.950). CONCLUSIONS: Since the system of diagnosis-related group offers a fixed amount of reimbursement for hernia repair (L. 3.247.000), the extensive use of tension free and sutureless methods, offers better profit for the Hospital. Last but not least, tension free hernia repair ensures short hospital stay, less postoperative pain, good compliance and better quality of life for the patient.

Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess.

Apparent mineralocorticoid excess (AME) is a genetic disorder causing pre- and postnatal growth failure, juvenile hypertension, hypokalemic metabolic alkalosis, and hyporeninemic hypoaldosteronism due to a deficiency of 11 beta-hydroxysteroid dehydrogenase type 2 enzyme activity (11 beta HSD2). The 11 beta HSD2 enzyme is responsible for the conversion of cortisol to the inactive metabolite cortisone and therefore protects the mineralocorticoid receptors from cortisol intoxication. Several homozygous mutations are associated with this potentially fatal disease. We have examined the phenotype, biochemical features, and genotype of 14 patients with AME. All of the patients had characteristic signs of a severe 11 beta HSD2 defect. Birth weights were significantly lower than those of their unaffected sibs. The patients were short, underweight, and hypertensive for age. Variable damage of one or more organs (kidneys, retina, heart, and central nervous system) was found in all of the patients except one. The follow-up studies of end-organ damage after 2-13 yr of treatment in six patients demonstrated significant improvement in all patients. The urinary metabolites of cortisol demonstrated an abnormal ratio with predominance of cortisol metabolites, i.e. tetrahydrocortisol plus 5 alpha-tetrahydrocortisol/tetrahydrocortisone was 6.7-33, whereas the normal ratio is 1.0. Infusion of [11-3H]cortisol resulted in little release of tritiated water, indicating the failure of the conversion of cortisol to cortisone. Thirteen mutations in the HSD11B2 gene have been previously published, and we report three new genetic mutations in two patients, one of whom was previously unreported. All of the patients had homozygous defects except one, who was a compound heterozygote. Our first case had one of the most severe mutations, resulting in the truncation of the enzyme 11 beta HSD2, and died at the age of 16 yr while receiving treatment. Three patients with identical homozygous mutations from different families had varying degrees of severity of clinical and biochemical features. Due to the small number of patients with identical mutations, it is difficult to correlate genotype with phenotype. In some cases, early and vigilant treatment of AME patients may prevent or improve the morbidity and mortality of end-organ damage such as renal or cardiovascular damage and retinopathy. The outcome of treatment in more patients may establish the efficacy of treatment.

[Risk of surgery in geriatric age: prospective evaluation of risk factors]. / Rischio chirurgico in età geriatrica: valutazione prospettica d'indici di rischio.

The use of Risk Index in surgery is aimed to plan surgical strategy in order to achieve a better post-operative prognosis. This is especially true in geriatric surgery where ASA Index and, more recently, Reiss Index are widely employed. Since the mentionated Risk Indices are calculated on the basis of different factors, in this prospective study we compared the two Risk Indices with the aim of verify which index offers better prognostic indications. 125 consecutive patients, aged older 70 years, undergoing surgical treatment, were investigated. The patients were grouped according to ASA Index and Reiss Index and postoperative morbidity and mortality rate was calculated. Both Indices resulted good predictive for the postoperative prognosis (ASA: G Statistic = 31.531, p < 0.001; Reiss: G Statistic = 18.416, p < 0.001), but ASA Index sensitivity was better (Specificity = 100%, sensitivity = 28%, false negative rate = 72%) than Reiss Index (Specificity = 100%, sensitivity = 0, false negative rate = 100%). Therefore ASA Index has clinical valid role in valuing surgical risk in elderly.