Microscopic dynamics of gas molecules confined in porous channel-like ice structure.

In the rich ice polymorphism landscape, ice XVII, metastable at ambient pressure and at temperatures below 130 K, is surely one of the most interesting from both fundamental and technological perspectives due to its porosity, i.e., its capability to repeatedly absorb and desorb molecular hydrogen by dosing the gas at pressures even below the ambient one. Here, owing to this exceptional key feature, we investigate the roto-vibrational dynamics of the H2 molecules trapped in the fully deuterated ice XVII structure. Making use of the high-resolution and brilliance of the TOSCA neutron vibrational spectrometer, combined with high-resolution Raman data, we are able to efficiently distinguish the center-of-mass translational bands from the rotational ones and to study them as a function of the guest filling of the ice structure, unraveling a peculiar behavior for the confined particle in a low-dimensional system. Moreover, we also report the study of the microscopic dynamics of confined nitrogen and oxygen, which are the most abundant molecular species in the atmosphere and are of paramount interest for technological applications. Finally, we show that the ice XVII porosity is a unique feature, especially in the low pressure regime, within the emptied-hydrate phases discovered to date.

Potential of acetaminophen on the sublingual microcirculation and peripheral tissue perfusion of febrile septic patients: prospective observational study.

BACKGROUND: Acetaminophen (ACT) has been studied in septic patients with detectable plasmatic levels of cell-free hemoglobin (Hb), where it demonstrated to inhibit the hemoprotein-mediated lipid peroxidation and oxidative injury, with a potential of beneficial effect on the endothelium. On the basis of this background, the aim of this study was to evaluate the sublingual microcirculation and the peripheral tissue perfusion before-and-after administration of ACT on clinical judgment in a cohort of febrile septic and septic shock patients. METHODS: Prospective observational study. 50 adult septic and septic shocks treated with ACT for pyrexia, where the sublingual microcirculation and the peripheral tissue perfusion with Near Infrared Spectroscopy (NIRS) and vascular occlusion test (VOT) were evaluated before ACT (t0), after 30 min (t1) and after 2 h (t2). Cell-free Hb and the markers of oxidative stress and endothelial damage were measured at t0 and t2. RESULTS: The study showed a significant increase of the density of the perfused small and total vessels of the sublingual microcirculation 30 min after the infusion of ACT; it also showed an increase of the Microvascular Flow Index (MFI) and a decrease in the heterogeneity of the flow. At a peripheral muscular level, we found an acceleration in the reperfusion curve after VOT at t1, expression of a higher reactivity of the microvasculature. CONCLUSIONS: ACT infusion did not show a clear correlation with cell-free Hb; however, it exhibited protective effect toward the microcirculation that was evident in particular in septic patients. This correlation merits further exploration.

Motorized spiral enteroscopy: effectiveness when used for new indications.

Background and study aims: Motorized spiral enteroscopy is proven to be effective in antegrade and retrograde enteroscopy. Nevertheless, little is known about its use in less common indications. The aim of this study was to identify new indications for the motorized spiral enteroscope. Methods: Monocentric retrospective analysis of 115 patients who underwent enteroscopy using PSF-1 motorized spiral enteroscope between January 2020 and December 2022. Results: A total of 115 patients underwent PSF-1 enteroscopy. 44 (38%) were antegrade procedures and 24 (21%) were retrograde procedures in patients with normal gastrointestinal anatomy with conventional enteroscopy indications. The remaining 47 (41%) patients underwent PSF-1 procedures for secondary less conventional indications: n=25 (22%) enteroscopy-assisted ERCP, n=8 (7%) endoscopy of the excluded stomach after Roux-en-Y gastric bypass, n=7 (6%) retrograde enteroscopy after previous incomplete conventional colonoscopy and n=7 (6%) antegrade panenteroscopy of the entire small bowel. In this group of secondary indications, technical success rate was significantly lower (72.5%) as compared to technical success rates in the conventional groups (98-100%, p<0.001 Chi-square). Minor adverse events occurred in 17/115 patients (15%), all treated conservatively (AGREE I and II). Conclusion: This study demonstrates the capabilities of PSF-1 motorized spiral enteroscope for secondary indications. PSF-1 is useful to complete colonoscopy in case of long redundant colon, to reach the excluded stomach after Roux-en-Y gastric bypass, to perform unidirectional pan-enteroscopy and to perform ERCP in patients with surgically altered anatomy. However, technical success rates are lower as compared to conventional antegrade and retrograde enteroscopy procedures, with only minor adverse events.

Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock.

BACKGROUND: Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient. METHODS: Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters. RESULTS: 8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes. CONCLUSIONS: Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result. TRIAL REGISTRATION: NCT02750163.

Microvascular dysfunction in pediatric patients with SARS-COV-2 pneumonia: report of three severe cases.

The coronavirus 19 (COVID-19) pandemic has affected hundreds of millions of people worldwide: in most of cases children and young people developed asymptomatic or pauci-symptomatic clinical pictures. However authors have showed that there are some categories of childhood more vulnerable to COVID-19 infection such as newborns or children with comorbidities. We report for the first time to the best of our knowledge about microvascular dysfunction in three pediatric clinical cases who developed COVID-19 infections with need of pediatric critical care. We found that sublingual microcirculation is altered in children with severe COVID-19 infection. Our findings confirmed most of data already observed by other authors in adult population affected by severe COVID-19 infection, but with distinct characteristics than microcirculation alterations previous observed in a clinical case of MIS-C. However we cannot establish direct correlation between microcirculation analysis and clinical or laboratory parameters in our series, by our experience we have found that sublingual microcirculation analysis allow clinicians to report directly about microcirculation dysfunction in COVID-19 patients and it could be a valuable bedside technique to monitor thrombosis complication in this population.

Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study.

PURPOSE: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. METHODS: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. RESULTS: Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22-4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23-3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23-3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49-79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69-38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38-22.09). CONCLUSION: Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. TRIAL REGISTRATION: Clinical trial registration number: NCT03354793.

Tocilizumab in COVID-19 interstitial pneumonia.

BACKGROUND: Published reports on tocilizumab in COVID-19 pneumonitis show conflicting results due to weak designs or heterogeneity in critical methodological issues. METHODS: This open-label trial, structured according to Simon's optimal design, aims to identify factors predicting which patients could benefit from anti-IL6 strategies and to enhance the design of unequivocal and reliable future randomized trials. A total of 46 patients with COVID-19 pneumonia needing of oxygen therapy to maintain SO2 > 93% and with recent worsening of lung function received a single infusion of tocilizumab. Clinical and biological markers were measured to test their predictive values. Primary end point was early and sustained clinical response. RESULTS: Twenty-one patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 h after tocilizumab infusion (P = 0.049) and higher baseline values of PaO2/FiO2 (P = 0.008) predicted a favourable response. CONCLUSIONS: Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in patients selected according to our inclusion criteria warrants investigations in randomized trials.

The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice.

Novel coronavirus 2019 is a single-stranded, ribonucleic acid virus that has led to an international pandemic of coronavirus disease 2019. Clinical data from the Chinese outbreak have been reported, but experiences and recommendations from clinical practice during the Italian outbreak have not. We report the impact of the coronavirus disease 2019 outbreak on regional and national healthcare infrastructure. We also report on recommendations based on clinical experiences of managing patients throughout Italy. In particular, we describe key elements of clinical management, including: safe oxygen therapy; airway management; personal protective equipment; and non-technical aspects of caring for patients diagnosed with coronavirus disease 2019. Only through planning, training and team working will clinicians and healthcare systems be best placed to deal with the many complex implications of this new pandemic.

The NATO project: nanoparticle-based countermeasures for microgravity-induced osteoporosis.

Recent advances in nanotechnology applied to medicine and regenerative medicine have an enormous and unexploited potential for future space and terrestrial medical applications. The Nanoparticles and Osteoporosis (NATO) project aimed to develop innovative countermeasures for secondary osteoporosis affecting astronauts after prolonged periods in space microgravity. Calcium- and Strontium-containing hydroxyapatite nanoparticles (nCa-HAP and nSr-HAP, respectively) were previously developed and chemically characterized. This study constitutes the first investigation of the effect of the exogenous addition of nCa-HAP and nSr-HAP on bone remodeling in gravity (1 g), Random Positioning Machine (RPM) and onboard International Space Station (ISS) using human bone marrow mesenchymal stem cells (hBMMSCs). In 1 g conditions, nSr-HAP accelerated and improved the commitment of cells to differentiate towards osteoblasts, as shown by the augmented alkaline phosphatase (ALP) activity and the up-regulation of the expression of bone marker genes, supporting the increased extracellular bone matrix deposition and mineralization. The nSr-HAP treatment exerted a protective effect on the microgravity-induced reduction of ALP activity in RPM samples, and a promoting effect on the deposition of hydroxyapatite crystals in either ISS or 1 g samples. The results indicate the exogenous addition of nSr-HAP could be potentially used to deliver Sr to bone tissue and promote its regeneration, as component of bone substitute synthetic materials and additive for pharmaceutical preparation or food supplementary for systemic distribution.

Severe 5,10-methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia.

BACKGROUND AND PURPOSE: Juvenile- or adult-onset forms of severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency manifesting as complicated hereditary spastic paraplegia have rarely been described. METHODS: Two siblings with mental retardation developed a progressive spastic paraparesis in their late teens. Their diagnostic assessment included extensive neurophysiologic, neuroimaging and metabolic studies. RESULTS: Brain magnetic resonance imaging showed occipital white matter alterations, and electromyography documented a mixed polyneuropathy. Severe hyperhomocisteinemia (>150 µmol/L) associated with the characteristic amino acid profile suggested a diagnosis of severe MTHFR deficiency, confirmed by MTHFR direct sequencing. Treatment with betaine and vitamins benefitted patients' symptoms and diagnostic features. CONCLUSIONS: Severe MTHFR deficiency can be a rare, treatable cause of autosomal recessive complicated hereditary spastic paraplegia. Its screening should be part of the diagnostic flowchart for these disorders.

An autonomous medical monitoring system: Validation on arrhythmia detection.

In this paper, we present a generic platform for autonomous medical monitoring and diagnostics. We validated the platform in the context of arrhythmia detection with publicly available databases. The big advantage of this platform is its capacity to deal with various types of physiological signals. Many pre-processing steps are performed to bring the input information into a uniform state that will be explored by a machine learning algorithm. Since this block plays a crucial role in the entire processing pipeline, three different methods were evaluated for detection and classification of anomalies. The results presented in this work are validated on cardiac beats, where the highest accuracy was obtained on the classification of normal beats (94%). On the other hand, atrial fibrillation and premature ventricular contraction beats were classified with an accuracy of 78%.

Resveratrol Requires Red Wine Polyphenols for Optimum Antioxidant Activity.

OBJECTIVE: There is substantial evidence that a diet rich in fruit and vegetables may reduce the risk of aging and stress oxidative associated diseases. It has been suggested that benefits associated with fruit and red wine consumption could be due to pooled antioxidant microcomponents in diet. The aim of this study was to investigate the antioxidant activities of pure resveratrol (a well known phytoalexin, RSV) and red wine polyphenols (RWP), using UV-B radiated isolated rat hepatocytes as a model of oxidative stress. METHODS: Rat hepatocytes were isolated by the collagenase method. The cells were loaded with resveratrol and/or polyphenols at different concentrations. The production of thiobarbituric acid reactive substances (TBARS) released by UV-B radiated cells and the levels of lipid-soluble antioxidants (Dolichol, Vitamin E, Coenzyme Q9 and Q10) were measured. RESULTS: Resveratrol had pro-oxidant or antioxidant effects depending on (lower or higher) dosage. RWP protection from photolipoperoxidation was dose-dependent and increased with dosage. Combination of the two compounds exhibited synergistic antioxidant effect, and made resveratrol effective both at lower and higher dosages. CONCLUSIONS: These results suggest that resveratrol requires red wine polyphenols for optimum antioxidant activity.

[Treatment with ranibizumab for choroidal neovascularization secondary to a pseudoxanthoma elasticum: Results of the French observational study PiXEL]. / Traitement par ranibizumab des néovascularisations choroïdiennes secondaires à un pseudoxanthome élastique : résultats de l'étude observationnelle française PiXEL.

INTRODUCTION: Pseudoxanthoma elasticum (PXE), a rare hereditary connective tissue disorder, may be complicated by angioid streaks (AS) and choroidal neovascularization (CNV), which may lead to irreversible loss of visual acuity (VA). Here we describe the safety and efficacy of ranibizumab in patients with CNV secondary to PXE. METHODS: A multicenter (n=23), observational study of a retrospective/prospective cohort, performed under real world conditions in France in all patients with CNV secondary to PXE who received at least one ranibizumab injection as of October 2011. The study objectives were to describe the mean annual number and reason for ranibizumab injections since initiation, evolution of best-corrected visual acuity (BCVA by Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and safety. RESULTS: Patients (n=72; 98 eyes) had a mean age of 59.6±8.3years and consisted of 54.2% men. The criterion for retreatment was based mainly on loss of VA, progression of CNV and angiographic leakage. CNV was primarily subfoveal or juxtafoveal (73.4%), and the initial mean VA was 64.6 ETDRS letters. On average, visual acuity of all eyes analyzed was relatively stable during the 2-year follow-up (62.3 letters vs 64.6 letters at the first injection), and 88.6% of eyes maintained VA between -15 and +15 letters or gained over 15 letters. No deaths or new intolerances were described. CONCLUSIONS: These results showed that ranibizumab was able to maintain stable VA in clinical practice for at least 2years in patients with CNV secondary to PXE, and to significantly reduce the frequency of neovascularization relapses, with a limited number of injections. The treatment was well tolerated by the patients.