Environmental study and stress-related biomarkers modifications in a crew during analog astronaut mission EMMPOL 6.

PURPOSE: Human presence in space is increasingly frequent, but we must not forget that it is a hostile environment. We aimed to study the characteristics of experimental scenarios, to obtain data on human response to isolation, disruption of circadian rhythm and high levels of psychophysical stress. METHODS: In these experiments, we evaluated stress response in five young healthy subjects inside an earth-based moon-settlement-like habitat during a 1-week long analog astronaut mission. Wearable devices were used to monitor daily step count of the subjects, physical activity, heart rate during physical exercise and at rest, and sleep parameters. From saliva and urine samples collected every day at awakening, we studied oxy-inflammation biomarkers and hormones (stress and appetite) were studied too. RESULTS: At the end of the week, all subjects revealed an increase in oxidative stress and cortisol levels but no inflammation biomarkers variations, in conjunction with increasing time/daily exercise. Furthermore, a significant decrease in hours of sleep/day, sleep quality, and REM phase of sleep was recorded and correlated with the increase of reactive oxygen species. CONCLUSION: Oxidative stress increased in a short period of time and may be attributed to the influence of psychological stress during confinement, as well as increased exercise and decreased amount of sleep. On a long-term basis, this could impact performance.

Arterial pulsation modulates the optical attenuation coefficient of skin.

Photoplethysmographic (PPG) signals arise from the modulation of light reflectivity on the skin due to changes of physiological origin. Imaging plethysmography (iPPG) is a video-based PPG method that can remotely monitor vital signs in a non-invasive manner. iPPG signals result from skin reflectivity modulation. The origin of such reflectivity modulation is still a subject of debate. Here, we have used optical coherence tomography (OCT) imaging to find whether iPPG signals may result from skin optical properties being directly or indirectly modulated by arterial transmural pressure propagation. The light intensity across the tissue was modeled through a simple exponential decay (Beer-Lambert law) to analyze in vivo the modulation of the optical attenuation coefficient of the skin by arterial pulsation. The OCT transversal images were acquired from a forearm of three subjects in a pilot study. The results show that the optical attenuation coefficient of skin changes at the same frequency as the arterial pulsation due to transmural pressure propagation (local ballistographic effect), but we cannot discard the contribution of global ballistographic effects.

Continuous Variable Entanglement in an Optical Parametric Oscillator Based on a Nondegenerate Four Wave Mixing Process in Hot Alkali Atoms.

We present the measurement of entanglement between twin beams generated with a doubly resonant optical parameter oscillator (OPO) based on four-wave mixing in hot ^{85}Rb vapor above threshold. This is the first measurement of entanglement in an OPO with a χ^{(3)} media above threshold. We reconstruct the covariance matrix for several configurations and based on a full picture of the four side band mode state, we study entanglement between all possible bipartitions. We show a robust generation of entanglement with stronger generation for a specific pair of modes. For this system, we show that atomic density is a determinant factor for the generation and loss of quantum correlations. The generation of entangled fields with an atomic OPO operating close to atomic resonance of alkali atoms enables a natural integration into quantum networks.

Low-temperature ordering of the dimer phase of a two-dimensional model of core-softened particles.

Purely pairwise interactions of the core-softened type, i.e., featuring a soft repulsion followed by a hard-core interaction at shorter distance, give rise to nontrivial equilibrium structures entirely different from the standard close packing of spheres. In particular, in a suitable low-temperature region of their phase diagram, such interactions are well known to favor a transition from a fluid to a cluster crystal. The residual mutual interaction between individual clusters can lead to the formation of patterns of their reciprocal orientations. In this work, we investigate two examples of such models in two dimensions, at the density most appropriate to the dimer phase, whereby clusters consist of just two particles, studying them with optimization techniques and Monte Carlo simulations. We focus on the dimer crystal, and unveil a second phase transition at extremely low temperature. This transition leads from a triangular dimer lattice with randomly disordered dimer orientations at high temperature to a reduced-symmetry ground state with nematic orientational order and a slightly distorted structure characterized by a centered-rectangular lattice at low temperature.

Effects of acute and sub-acute hypobaric hypoxia on oxidative stress: a field study in the Alps.

PURPOSE: High altitude results in lower barometric pressure and hence partial pressure of O2 decrease can lead to several molecular and cellular changes, such as generation of reactive oxygen species (ROS). Electron Paramagnetic Resonance technique was adopted in the field, to evaluate the effects of acute and sub-acute hypobaric hypoxia (HH) on ROS production by micro-invasive method. Biological biomarkers, indicators of oxidative stress, renal function and inflammation were investigated too. METHODS: Fourteen lowlander subjects (mean age 27.3 ± 5.9 years) were exposed to HH at 3269 m s.l. ROS production, related oxidative damage to cellular components, systemic inflammatory response and renal function were determined through blood and urine profile performed at 1st, 2nd, 4th, 7th, and 14th days during sojourn. RESULTS: Kinetics of changes during HH exposition showed out significant (range p < 0.05-0.0001) increases that at max corresponds to 38% for ROS production rate, 140% for protein carbonyl, 44% for lipid peroxidation, 42% for DNA damage, 200% for inflammatory cytokines and modifications in renal function (assessed by neopterin concentration: 48%). Conversely, antioxidant capacity significantly (p < 0.0001) decreased - 17% at max. CONCLUSION: This 14 days in-field study describes changes of oxidative-stress biomarkers during HH exposure in lowlanders. The results show an overproduction of ROS and consequent oxidative damage to protein, lipids and DNA with a decrease in antioxidant capacity and the involvement of inflammatory status and a transient renal dysfunction. Exposure at high altitude induces a hypoxic condition during acute and sub-acute phases accompanied by molecular adaptation mechanism indicating acclimatization.

Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population.

Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.

The use of oxygen ozone therapy in the treatment of cervicobrachial pain: case series study.

This retrospective, observational, uncontrolled case series study was carried out to evaluate the clinical efficacy and safety of intramuscular paravertebral injections of an oxygen-ozone (O2-O3) mixture in patients with cervicobrachial pain. One hundred and sixty-eight subjects affected by cervicobrachial pain, referred to Ozone Therapy Unit at San Pietro Fatebenefratelli Hospital in Rome (Italy), were enrolled in the study. All the subjects (n=168, 106 females and 62 males) completed the treatment and the follow-up visits. Subjects received 12 cervical intramuscular injections of an O2-O3 mixture (5 mL) with an O3 concentration of 16 µg/mL once a week. The overall reduction of pain was measured by the change in mean of Visual Analogue Scale (VAS) score from baseline to the end of treatment and from baseline to one, two, three, four and five years of follow-up. Patient satisfaction was assessed at the end of treatment, by modified MacNab Questionnaire. Possible adverse events related to the treatment were recorded. The mean (± standard deviation) VAS pain score at baseline, at the end of treatment, and during the follow-up at one, two, three, four and five years were 7.82 (±1), 1.6 (±1.5), 1.5 (±1.4), 1.4 (±1.3), 1.6 (±1.2), 1.5 (±1.3) and 1.60 (±1.2), respectively, showing a significant reduction in pain over time (p<0.001). Of 156 patients who responded to treatment, 128 (82.05%) were pain free at one year, 110 (70.51%) at second year, 103 (66.02%) at third year, 94 (60.25%) at fourth year and 86 (55.12%) at fifth year follow-up visit. According to pain distribution all subjects showed a significant reduction in pain over time in each group (p<0.05). No significant differences were observed between groups. No serious adverse events were observed during the entire study. We suggest the use of intramuscular paravertebral injections of an oxygen-ozone (O2-O3) mixture in patients with cervicobrachial pain as an effective and safe treatment option to consider before surgical intervention.

Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity.

Serogroup B meningococcus (MenB) is a leading cause of meningitis and sepsis across the world and vaccination is the most effective way to protect against this disease. 4CMenB is a multi-component vaccine against MenB, which is now licensed for use in subjects >2 months of age in several countries. In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults. The resulting 4CMenB protein antigen fingerprinting allowed the identification of specific human antibody repertoire correlating with the bactericidal response elicited in each subject. This work represents an example of epitope mapping of the immune response induced by a multicomponent vaccine in different age groups with the identification of protective signatures. It shows the high flexibility of this microarray based methodology in terms of high-throughput information and minimal volume of biological samples needed.

Quantum Noise Correlations of an Optical Parametric Oscillator Based on a Nondegenerate Four Wave Mixing Process in Hot Alkali Atoms.

We present the first measurement of two-mode squeezing between the twin beams produced by a doubly resonant optical parameter oscillator (OPO) in an above threshold operation based on parametric amplification by nondegenerate four wave mixing with rubidium (^{85}Rb). We demonstrate a maximum intensity difference squeezing of -2.7 dB (-3.5 dB corrected for losses) with a pump power of 285 mW and an output power of 12 mW for each beam, operating close to the D1 line of Rb atoms. The use of open cavities combined with the high gain media can provide a strong level of noise compression and the access to new operation regimes that could not be explored by crystal based OPOs. The spectral bandwidth of the squeezed light is broadened by the cavity dynamics, and the squeezing level is robust for strong pump powers. Stable operation was obtained up to 4 times above the threshold. Moreover, operation of the OPO close to the atomic resonances of alkali atoms allows a natural integration into quantum networks, including structures such as quantum memories.

Oxygen-ozone therapy as adjuvant in the current emergency in SARS-COV-2 infection: a clinical study.

The aim of the multicentre study promoted by Nuova FIO is to evaluate the beneficial effects of the systemic Oxygen-Ozone (O2O3) therapy in patients suffering from SARS COV-2 disease in the early phases of the disease, before worsening, up to the need of tracheal intubation. The study is based on the rationale on that the systemic oxygen-ozone treatment could be effective, positively influencing the disease evolution and/or being able to mitigate the onset of the cytokine storm syndrome at least partially.

Improvement of body composition and bone mineral density after enteral nutrition in pediatric Crohn disease.

BACKGROUND: The relationship between exclusive enteral nutrition (EEN) and bone status is poorly defined in pediatric Crohn disease (CD). AIMS: The aim of this study was to investigate the impact of EEN on body composition, nutritional status, and bone mineral density (BMD) in an incident CD cohort. METHODS: 18 newly diagnosed CD children starting EEN for 8 weeks were prospectively enrolled and evaluated at baseline and after 8 (T8), 26 (T26) and 52 weeks (T52) from diagnosis. The Fat Free Mass (FFM) and the Resting Energy Expenditure (REE) were measured through Bioelectrical Impedance (BIA) and the BMD was assessed by dual-energy X-ray (DXA). We compared DXA data of IBD patients to the data obtained in 15 healthy controls. RESULTS: CD children had a significant lower BMD compared to healthy control both at baseline (p<0.0001), and after EEN therapy at T52 (p=0.0004); although at this latest time point CD children had a significant increase of BMD compared to baseline (p=0.0015). The BIA analysis showed a significant increase at T26 and T52 of FFM and REE. T52. FFM measured by BIA and BMD measured by DXA were significantly correlated. CONCLUSION: EEN improves nutritional status and bone mineral composition.

Reducing the phase noise in diode lasers.

Diode lasers are widely used in atomic physics given their narrow linewidth and wavelength tunability. Nevertheless, although they present low noise for their intensity, excessive noise in the phase limits their application in quantum optics. Looking for reduction of this phase noise, we built and characterized a ring laser, using a semiconductor-tapered amplifier as the gain medium. We were able to reduce the phase noise of a diode laser to a factor of 10 above shot-noise level, bringing it closer to a useful coherent state for applications in quantum information.

Hexapartite Entanglement in an above-Threshold Optical Parametric Oscillator.

We demonstrate, theoretically and experimentally, the generation of hexapartite modal entanglement by the optical parametric oscillator (OPO) operating above the oscillation threshold. We show that the OPO generates a rich structure of entanglement among sets of six optical sideband modes interacting through the nonlinear crystal. The class of quantum states thus produced can be controlled by a single parameter, the power of the external laser that pumps the system. Our platform allows for the generation of massive entanglement among many optical modes with well defined but vastly different frequencies, potentially bridging nodes of a multicolor quantum network.

Orbital angular momentum symmetry in a driven optical parametric oscillator.

We investigate the dynamics of a driven optical parametric oscillator under the injection of orbital angular momentum. The injected mode is adiabatically driven through arbitrary transformations on the Poincaré sphere of first-order paraxial beams. As a result, the down-converted beam conjugated to the seed is shown to follow a path imposed by a nontrivial symmetry on the Poincaré sphere. This symmetry allows controllable distinguishability between the spatial modes of the down-converted beams. In this Letter, we provide convincing experimental evidence of this effect.

Randomised Italian Sonography for occiput POSition Trial Ante vacuum (R.I.S.POS.T.A.).

OBJECTIVE: To assess whether sonographic diagnosis of fetal head position before instrumental vaginal delivery can reduce the risk of failed vacuum extraction and improve delivery outcome. METHODS: Randomised Italian Sonography for occiput POSition Trial Ante vacuum (R.I.S.POS.T.A.) is a randomized controlled trial of term (37 + 0 to 41 + 6 weeks' gestation) singleton pregnancies with cephalic presentation requiring instrumental delivery by vacuum extraction, which was conducted between April 2014 and June 2017 and involved 13 Italian maternity hospitals. Patients were randomized to assessment of fetal head position before attempted instrumental delivery by either vaginal examination (VE) alone or VE plus transabdominal sonography (TAS). Primary outcome was incidence of emergency Cesarean section due to failed vacuum extraction. A sample size of 653 women per group was planned to compare the primary outcome between the two groups. The sample size estimation was based on the hypothesis that the risk of failed vacuum delivery in the VE group would be 5% and that ultrasound assessment of fetal position prior to vacuum extraction would decrease this risk to 2%. RESULTS: On interim analysis, the trial was stopped for futility. During this period, 222 women were randomized and 221 were included in the final data analysis, of whom 132 (59.7%) were randomized to evaluation of fetal head position by VE only and 89 (40.3%) to assessment by VE plus TAS prior to vacuum extraction. No significant differences were observed between the two groups with respect to incidence of emergency Cesarean section due to failed instrumental delivery and other maternal and fetal outcomes. Women randomized to assessment by VE plus TAS showed higher incidence of non-occiput anterior position of the fetal head at randomization and lower incidence of incorrect diagnosis of occiput position compared with women undergoing assessment by VE alone. A higher rate of episiotomy was noted in the women undergoing both VE and TAS compared with those in the VE-only group. CONCLUSIONS: Our prematurely discontinued randomized controlled trial did not demonstrate any benefit in terms of reduced risk of failed instrumental delivery or maternal and fetal morbidity in women undergoing sonographic assessment of fetal head position prior to vacuum extraction. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Focus on periodontal disease and development of endocarditis.

Infective endocarditis is a devastating disease with high morbidity and mortality. The link to oral bacteria has been known for many decades and has caused ongoing concern for dentists, patients and cardiologists. The microbiota of the mouth is extremely diverse and more than 700 bacterial species have been detected. Half of them are uncultivable so far. Oral microbiota is not uniform, specific sites exist in the mouth such as tongue, palate, cheek, teeth and periodontal pockets that have their own microbiota. Factors involved in the development of a bacterial endocarditis are difficult to define but a vulnerable surface (i.e. a damaged endocardium) and a high bacterial load in the blood seems to be decisive. The cause of microorganisms, in 90% of cases, are staphylococcus, streptococcus and enterococcus. Oral streptococci belong to viridans group (streptococcus mutans and streptococcus sanguis). As they are part of dental plaque, they could enter the bloodstream causing bacteraemia through daily habits like chewing or tooth brushing. Effective treatment of periodontal infections is important to reduce local inflammation and bacteraemia. In addition, poor periodontal health appears to increase the risk of cardiovascular disease, pulmonary disease, and preterm and low birth weight. CONCLUSIONS: Long-standing oral disease prevention protocols reduce the risk of developing periodontal disease. Data suggests that methods used to prevent cases of IE that originate from oral bacteria should focus on improving oral hygiene and reducing or eliminating gingivitis, which should reduce the incidence of bacteraemia after tooth-brushing and the need to extract teeth owing to periodontal disease and caries.

Detection of endocarditis bacteria in tonsillar mucosa of Afghan population.

Endocarditis is a cardiovascular disease caused by the inflammation of the inner tissues of the heart, the endocardium, usually of the valves. Bacteraemia is essential in the development of endocarditis, and there are some findings that the main pathogens of endocarditis are viridans group streptococci: Streptococcus oralis, Streptococcus sanguinis, and Enterococcus faecalis. There is strong evidence that endocarditis bacteria are present in the tonsillar microbiota, so that tonsillar infection is associated with an increased risk of endocarditis. The aim of this manuscript is to investigate the presence of the main pathogens of endocarditis in tonsillar microbiota of an Afghan population group. A sample of 80 tonsil swabs were analyzed by quantitative real time PCR to detect endocarditis pathogens and an estimation of the total bacterial load. The median bacterial load in PCR reaction was 1.4x106 (interquartile range 4,7x105 - 2,9x106). Three species, S. Oralis, S. Sanguinis, and E. Faecalis were found in large amounts in all specimens. On the other hand, S. Mitis was never detected. The S. Aureus was found in 3 samples with a prevalence of 0.04 (C.I. 0.01-0.10). The S. Mutans was found in 33 samples with a prevalence of 0.41 (C.I. 0.31-0.52). Endocarditis bacteria has been found into the tonsillar microbiota, so there is sufficient evidence to justify that the oral cavity is a reservoir of endocarditis bacteria that can have a significant impact on the cardiovascular function.

Human polyomavirus in tonsillar microbiota of an Afghan population group.

Some studies have evidenced the role of human polyomaviruses in head and neck squamous cell carcinoma. BK, JC and SV40 human polyoma viruses are widely recognized as etiological agents associated with malignancies. The aim of this study was to analyse the prevalence of BK, IC and SV40 in tonsillar microbiota in a group of Afghan volunteers. A sample of the tonsillar microbiota was taken from a single site using a sterile oral swab paper stick. A fixed volume of purified DNA from each sample was tested by quantitative real-time polymerase chain reactions to evaluate the number of human cells and the number of viral genomes in each sample. The cell number was evaluated via the quantification of a single copy genomic sequence, which is located in the HMBS locus. The median analyzed cell number in each reaction was 4343 (interquartile range 2074-8470). SV40 was never detected, while prevalence rate was 0.11 (C.I. 0.06-0.20) for BK and 0.10 (C.I. 0.05-0.19) for JC. Further studies are necessary to clarify whether polyomaviruses can be considered a risk factor of oral, oropharyngeal and laryngeal malignancies.

Pre-treatment with berberine enhances effect of 5-fluorouracil and cisplatin in HEP2 laryngeal cancer cell line.

Larynx squamous cell carcinoma represents one of the most common head and neck cancers in the world. Herbal drugs are popularly emerging as complementary and alternative therapies in cancer because of their cost effectiveness and minimal side effects. The present study was undertaken to explore the anti-tumor potential of berberine, an isoquinolone present in the extract of Tinospora cordifolia in HEP2 human laryngeal cancer cell line. Besides, it was aimed to investigate whether berberine could enhance the anti-cancer effect of 5-fluorouracil and cisplatin in HEP2. Our data seem to support a role for berberine in decreasing the expression of genes usually seen overexpressed in larynx squamous cell carcinoma and involved in pathways such as those of cell cycle and regulation, differentiation, and epithelial-mesenchymal transition. Moreover, a down regulation of these genes caused by cisplatin or 5-fluorouracil, treatment of election in laryngeal cancers was enhanced by a 4h pre-treatment with berberine.

Efficacy of a standardized extract of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) in infantile colic: An open randomized controlled trial.

BACKGROUND: Infant colic (IC) is a prevalent physiological event of infants, which can disrupt the child's home environment. We aimed to investigate the effectiveness of a mixture of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) compared with Lactobacillus reuteri DSM 17938 and with simethicone for the treatment of IC. METHODS: A multicenter randomized comparative study was conducted in infants with colic, according to Rome III criteria, who were randomly assigned to receive M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) (Colimil® Plus® ; Milte Italia Spa, Milan, Italy) (Group A), L. reuteri DSM 17938 (Group B) and simethicone (Group C). Treatment was given to subjects for 28 days. KEY RESULTS: One-hundred and seventy-six patients completed the study. Mean daily crying time at day 28 was significantly lower in group A (-44, 95% CI: -58 to -30, P<.001) and group B (-35, 95% CI: -49 to -20, P<.001) when compared to group C. No significant difference was observed between Group A and Group B (mean difference: -9 minutes, 95% CI -23 to +5, P=.205). At day 28, 39 of 57 (68.4%) of infants in Group C responded to the treatment compared with 57 out of 60 patients (95%) of Group A and 51 out of 59 (86.4%) of Group B (P<.001). CONCLUSIONS: This study suggests that administration of M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) and L. reuteri DSM 17938 are significantly more effective than simethicone in IC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02708238.