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BACKGROUND: Antioxidant administration can significantly alleviate smoking-mediated oxidative stress. In our previous research, using a concentrated mixed juice powder led to significant reduction in oxidative status markers and improved lung function among smokers. OBJECTIVE: To compare the effectiveness of different antioxidant formulations of the retail product Juice Plus+® on oxidative status and lung function in healthy smokers via a a Bayesian Network (BN) analysis. METHODS: At baseline and after 3 months' supplementation, pulmonary function, cardiovascular risk factors, and oxidative status were assessed in 101 smokers, randomized into three groups: placebo (P), fruit/vegetable (FV), and fruit/vegetable/berry (FVB) group. BN analysis was performed via Monte Carlo simulations. Statistical significance was assigned as p < 0.05. RESULTS: No significant interaction was observed in P (network score –101.4, p = ns), whereas overall fit significantly improved in both FV (network score –185.7, p = 0.01) and FVB (–293.7, p = 0.003). Moreover, P group's respiratory parameters appeared unrelated to the biochemical structure, whereas those of the FV and, to a greater extent, FVB groups were definitely related to it CONCLUSIONS: BN analysis demonstrated that the FV and FVB formulations contain nutraceutical compounds capable of synergistically acting and improving antioxidant modulation and respiratory function in smoking subjects [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Several specific assays are commercially available to determine dabigatran anticoagulant activity. Aims of this multicenter and multiplatform study were to compare five methods for dabigatran measurement and investigate their performances in the low concentration range. Methods: Dabigatran levels were analyzed in 295 plasma samples from patients enrolled in the START‐Laboratory Register by the following methods using dedicated calibrators and controls: STA‐ECA II (Diagnostica Stago), standard and low range Hemoclot Thrombin Inhibitors (Hyphen BioMed), Direct Thrombin Inhibitor Assay (Instrumentation Laboratory), Direct Thrombin Inhibitor Assay (Siemens), Technoclot DTI (Technoclone). Results: Methods showed variable agreement with the Hemoclot Thrombin Inhibitors assay used as reference test, with modest under‐ or overestimations (Bland‐Altman bias from −17.3 to 4.0 ng/mL). Limits of detection and quantification varied depending on the assay (4‐52 and 7‐82 ng/mL, respectively). Between‐run precision and accuracy were good for all methods for both quality control levels. Assay's repeatability assessed at very low dabigatran concentrations (from 10 to 60 ng/mL) was also acceptable, variability generally increased at lower drug levels. Conclusion: The five dabigatran‐specific assays evaluated in this study provided reliable assessment of dabigatran plasma levels, although showing different performances. [ABSTRACT FROM AUTHOR]

PURPOSE: To provide information on the role of the metabolic syndrome on prostate cancer risk. METHODS: We examined data from a multicentric Italian case-control study. Cases were 1294 patients with incident, histologically confirmed prostate cancer. Controls were 1451 men hospitalized with acute, non-neoplastic conditions. All subjects were younger than 75 years. The metabolic syndrome was defined according to selected indicators of abdominal obesity, hypercholesterolemia, hypertension, and diabetes. We computed multivariate odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression. RESULTS: Considering separate components of the metabolic syndrome, the ORs were 0.98 (95% CI, 0.72-1.34) for diabetes, 1.14 (95% CI, 0.96-1.36) for hypertension, 1.54 (95% CI, 1.26-1.89) for hypercholesterolemia, and 1.02 (95% CI, 0.86-1.21) for abdominal obesity. The OR of prostate cancer was 1.66 (95% CI, 1.22-2.28) in men with metabolic syndrome compared with those without. We found ORs of 1.02 (95% CI, 0.83-1.26) for men with one component of the metabolic syndrome, 1.12 (95% CI, 0.89-1.42) for two, 1.65 (95% CI, 1.15-2.36) for three, and 3.99 (95% CI, 1.03-15.4) for four compared with no components. CONCLUSIONS: The metabolic syndrome was associated with the risk of prostate cancer in this population. [ABSTRACT FROM AUTHOR]

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., (© 2024. The Author(s).)

Abstract: Treatment with direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) is effective and safe. However, bleeding complications still occur. Whether DOAC level measurement may further improve treatment efficacy and safety is still an open issue. In the "Measure and See" study, venous blood was collected 15-30 days after DOAC initiation in patients with AF who were then followed up for 1 year to record the occurrence of major and clinically relevant nonmajor bleeding. DOAC plasma levels were measured in 1 laboratory, and results were kept blind to patients and treating doctors. Trough DOAC levels were assessed in 1657 patients (957 [57.7%] and 700 patients treated with standard and low-dose, respectively). Fifty bleeding events were recorded during 1606 years of follow-up (3.11% pt/yrs). Fifteen bleeding events (4.97% pt/yrs) occurred in patients with C-trough standardized values in the highest activity class (>0.50), whereas 35 events (2.69% pt/yrs) occurred in those with values in the 2 lower classes (≤0.50, P = .0401). Increasing DOAC levels and low-dose DOAC use were associated with increased bleeding risk in the first 3 months of treatment. Overall, 19% of patients receiving low doses had standardized values in the highest class. More bleeding occurred in patients on low (4.3% pt/yrs) vs standard (2.2% pt/yrs; P = .0160) dose DOAC. Early measurement of DOAC levels in patients with AF identified many individuals with high levels despite the low doses use and had more bleeding risk during the first 3 months of treatment. This trial was registered at www.ClinicalTrials.gov as #NCT03803579., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Alcohol abuse is one of the most common causes of mortality worldwide. This study aimed to investigate the efficacy of a treatment in reducing circulating ethanol and oxidative stress biomarkers., Methods: Twenty wine-drinking subjects were investigated in a randomized controlled, single-blind trial (ClinicalTrials.gov. Identifier: NCT06548503; Ethical Committee of the University of Padova (HEC-DSB/12-2023) to evaluate the effect of the intake of a product containing silymarin, pyrroloquinoline quinone sodium salt, and myricetin (referred to as Si.Pi.Mi. for this project) on blood alcohol, ethyl glucuronide (EtG: marker for alcohol consumption) and markers of oxidative stress levels (Reactive Oxygen Species-ROS, Total Antioxidant Capacity-TAC, CoQ10, thiols redox status, 8-isoprostane, NO metabolites, neopterin, and uric acid). The effects of the treatment versus placebo were evaluated acutely and after 1 week of supplementation in blood and/or saliva and urine samples., Results: Si.Pi.Mi intake reduced circulating ethanol after 120 min (-33%). Changes in oxidative stress biomarkers, particularly a TAC (range +9-12%) increase and an 8-isoprostane (marker of lipidic peroxidation) decrease (range -22-27%), were observed too., Conclusion: After the administration of Si.Pi.Mi, the data seemed to suggest a better alcohol metabolism and oxidative balance in response to wine intake. Further verification is requested.

Abstract: Although effective and safe, treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) is still associated with thrombotic complications. Whether the measurement of DOAC levels may improve treatment efficacy is an open issue. We carried out the observational, prospective, multicenter Measure and See (MAS) study. Blood was collected 15 to 30 days after starting DOAC treatment in patients with AF who were followed-up for 1 year. Plasma samples were centralized for DOAC level measurement. Patients' DOAC levels were converted into drug/dosage standardized values to allow a pooled analysis in a time-dependent, competitive-risk model. The measured values were transformed into standardized values (representing the distance of each value from the overall mean) by subtracting the DOAC-specific mean value from the original values and dividing by the standard deviation. Trough and peak DOAC levels were assessed in 1657 and 1303 patients, respectively. In total, 21 thrombotic complications were recorded during 1606 years of follow-up (incidence of 1.31% of patients per year). Of 21 thrombotic events, 17 occurred in patients whose standardized activity levels were below the mean of each DOAC (0); the incidence was the highest (4.82% of patients per year) in patients whose standardized values were in the lowest class (-1.00 or less). Early measurement of DOAC levels in patients with AF allowed us to identify most of the patients who, having low baseline DOAC levels, subsequently developed thrombotic complications. Further studies are warranted to assess whether thrombotic complications may be reduced by measuring baseline DOAC levels and modifying treatment when indicated. This trial was registered at www.ClinicalTrials.gov as #NCT03803579., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19. We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O 2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT). Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1&#95;pre (basal level) and at T2&#95;pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation.

An imbalance of oxy-inflammation status has been involved in axonal damage and demyelination in multiple sclerosis (MS). The aim of this study was to investigate the efficacy of an antioxidant treatment (calcium disodium ethylenediaminetetracetic acid-EDTA) chelation therapy associated with a micronutrient complex in MS patients. A total of 20 MS patients and 20 healthy subjects, enrolled as a control group (CTR), were recruited. We measured the plasma ROS production and total antioxidant capacity (TAC) by a direct assessment using Electron Paramagnetic Resonance; activities of the antioxidant system (thiols' redox status and enzymes); and the urinary presence of biomarkers of oxidative stress by immunoenzymatic assays. We also evaluated the levels of inflammation by plasmatic cytokines (TNFα, IL-1β, and IL-6) and assessed the sICAM levels, as well as the nitric oxide (NO) catabolism and transthyretin (TTR) concentration. Comparing CTR and MS, in the latter ROS production, oxidative damage, inflammatory biomarkers, and NO metabolite concentrations results were significantly higher, while TAC was significantly lower. Treatment in MS induced significant ( p < 0.05) down-regulating of pro-inflammatory sICAM1, TNF-α, IL6, as well as biomarkers of lipid peroxidation and DNA damage production. The protective effect exhibited may occur by decreasing ROS production and increasing antioxidant capacity, turning into a more reduced thiols' status.

Functional movement disorders (FMD) are characterized by the presence of neurological symptoms that cannot be explained by typical neurological diseases or other medical conditions. First evidence showed that, compared to healthy controls (CTR), FMD patients presented increased levels of glutamate+glutamine in the anterior cingulate cortex/medial prefrontal cortex, and decreased levels of glutamate in the cerebrospinal fluid, suggesting that a glutamatergic dysfunction might play a role in FMD pathophysiology. In this study, 12 FMD patients and 20 CTR were recruited and underwent venous blood sampling and urine collection: levels of glutamate, BDNF, dopamine, oxidative stress, creatinine, neopterin, and uric acid were analyzed. Participants also underwent a psychometric assessment investigating depression, anxiety, and alexithymia. We found that levels of glutamate, BDNF, and dopamine were significantly lower in the blood of FMD patients than CTR. Glutamate and dopamine levels were positively associated with levels of alexithymia. Our findings give further evidence that glutamatergic dysfunction might be involved in the pathophysiology of FMD, possibly representing a biomarker of disease; moreover, since glutamatergic and dopaminergic systems are closely interconnected, our results might have a relevance in terms of treatment options for FMD patients., (© 2023. The Author(s).)

Freeskiing is performed in an extreme environment, with significant physical effort that can induce reactive oxygen species (ROS) generation and dehydration. This study aimed to investigate the evolution of the oxy-inflammation and hydration status during a freeskiing training season with non-invasive methods. Eight trained freeskiers were investigated during a season training: T0 (beginning), T1-T3 (training sessions), and T4 (after the end). Urine and saliva were collected at T0, before (A) and after (B) T1-T3, and at T4. ROS, total antioxidant capacity (TAC), interleukin-6 (IL-6), nitric oxide (NO) derivatives, neopterin, and electrolyte balance changes were investigated. We found significant increases in ROS generation (T1A-B +71%; T2A-B +65%; T3A-B +49%; p < 0.05-0.01) and IL-6 (T2A-B +112%; T3A-B +133%; p < 0.01). We did not observe significant variation of TAC and NOx after training sessions. Furthermore, ROS and IL-6 showed statistically significant differences between T0 and T4 (ROS +48%, IL-6 +86%; p < 0.05). Freeskiing induced an increase in ROS production, which can be contained by antioxidant defense activation, and in IL-6, as a consequence of physical activity and skeletal muscular contraction. We did not find deep changes in electrolytes balance, likely because all freeskiers were well-trained and very experienced.

Background: Recent reports suggest that direct oral anticoagulants (DOAC) may induce different anticoagulant and profibrinolytic responses. We performed a head-to-head comparison of the changes in thrombin generation (TG) parameters and tissue plasminogen activator (t-PA)-induced clot lysis produced by different DOAC., Material and Methods: We tested 137 plasma samples from patients with non-valvular atrial fibrillation (n=72) and venous thromboembolism (n=65) under treatment with apixaban (n=38), edoxaban (n=29), rivaroxaban (n=39), or dabigatran (n=31). TG was evaluated by a fluorometric assay and fibrinolysis by measuring the lysis time of clots exposed to 40 ng/mL t-PA., Results: Trough-to-peak changes of TG parameters, along with correlation analysis, showed that all DOAC prolonged the lag-time in a concentration-dependent fashion. As for the other parameters, anti-factor Xa drugs markedly reduced the thrombin peak and velocity index but had little (rivaroxaban) or no effect on endogenous thrombin potential (ETP); dabigatran, instead, reduced ETP, weakly decreased thrombin peak and did not influence the velocity index, as also inferred from the changes in TG values after neutralisation of dabigatran with idarucizumab. Concerning the profibrinolytic effect of DOAC, intergroup comparison showed that the clot lysis time of dabigatran samples was significantly shorter than that of the apixaban and rivaroxaban samples, at both C-Trough and C-Peak. Moreover, a significant correlation between trough-to-peak changes in drug level and clot lysis time was only observed in the dabigatran group (rho=0.53). Finally, after DOAC removal by DOAC-stop, only dabigatran samples showed a significant increase in lysis time., Discussion: Our data show that dabigatran inhibits TG in a different way than anti-Xa DOAC; moreover, under our conditions, only dabigatran displayed profibrinolytic activity, most likely because of its distinctive effect on the TG curve.

Concordia Station is the permanent, research station on the Antarctic Plateau at 3230 m. During the eleventh winter-over campaign (DC11-2015; February 2015 to November 2015) at Antarctic Concordia Station, 13 healthy team members were studied and blood samples were collected at six different time points: baseline measurements (T0), performed at sea level before the departure, and during the campaign at 3, 7, 20, 90, and 300 days after arrival at Concordia Station. Reducing the partial pressure of O 2 as barometric pressure falls, hypobaric hypoxia (HH) triggers several physiological adaptations. Among the others, increased oxidative stress and enhanced generation of reactive oxygen/nitrogen species (ROS/RNS), resulting in severe oxidative damage, were observed, which can share potential physiopathological mechanisms associated with many diseases. This study characterized the extent and time-course changes after acute and chronic HH exposure, elucidating possible fundamental mechanisms of adaptation. ROS, oxidative stress biomarkers, nitric oxide, and proinflammatory cytokines significantly increased (range 24-135%) during acute and chronic hypoxia exposure (peak 20 th day) with a decrease in antioxidant capacity (peak 90 th day: -52%). Results suggest that the adaptive response of oxidative stress balance to HH requires a relatively long time, more than 300 th days, as all the observed variables do not return to the preexposition level. These findings may also be relevant to patients in whom oxygen availability is limited through disease (i.e., chronic heart and lung and/or kidney disease) and/or during long-duration space missions., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Simona Mrakic-Sposta et al.)

Competitive Offshore Ocean Sailing is a highly demanding activity in which subjects are exposed to psychophysical stressors for a long time. To better define the physiological adaptations, we investigated the stress response of subjects exposed to 3-days long ocean navigation with disruption of circadian rhythms. 6 male subjects were involved in the study and provided urine and saliva samples before setting sail, during a single day of inshore sailing, during 3-days long ocean navigation, and at the arrival, to measure oxidative stress, cortisol, nitric oxide metabolites (NOx) and metabolic response. Motion Sickness questionnaires were also administered during the navigation. The crew suffered a mean weight loss of 1.58 kg. After the long navigation, a significant increase in ROS production and decrease in total antioxidant capacity and uric acid levels were observed. Lipid peroxidation, NO metabolites, ketones, creatinine, and neopterin levels were also increased. Furthermore, a significant increase in cortisol levels was measured. Finally, we found a correlation between motion sickness questionnaires with the increase of NOx, and no correlation with cortisol levels. Physical and psychological stress response derived from offshore sailing resulted in increased oxidative stress, nitric oxide metabolites, and cortisol levels, unbalanced redox status, transient renal function impairment, and ketosis. A direct correlation between motion sickness symptoms evaluated through questionnaires and NOx levels was also found., (© 2022. The Author(s).)

Introduction: Double centrifugation before freezing is recommended before thrombin generation assays (TGA). However, this procedure is not mandatory for routine hemostasis tests, precluding the use of these samples for TGA. The aim of this study is to assess the impact of single and double centrifugation on TGA performed on frozen samples from healthy volunteers (HVs) and patients receiving direct oral anticoagulants (DOACs)., Methods: Forty HVs and 57 patients receiving a DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) were included in this prospective double-center observational study. Blood was collected into 109 mmol/L citrated tubes and frozen at -70°C before TGA using ST Genesia with STG-DrugScreen reagent. Four pre-analytical conditions were studied: (A) single centrifugation (2000 g, 15 minutes) before freezing; (B) one centrifugation before freezing and another after thawing (2000 g, 15 minutes for both); (C) one centrifugation before freezing(2000 g, 15 minutes) and another after thawing (2000 g, 10 minutes); (D) double centrifugation (2000 g, 15 minutes) before freezing (reference). Centrifugation conditions (A), (B), and (C) were compared with the reference condition (D). Acceptable relative differences were defined at 6%, 8%, and 10% for normalized lag time, endogenous thrombin potential, and peak height, respectively., Results: Centrifugation conditions had a small but acceptable impact on HVs samples, but single centrifugation always resulted in unacceptable reductions in normalized lag times for DOAC samples. A second centrifugation after thawing permitted the recovery of acceptable differences for the three TGA parameters for edoxaban but not for apixaban, rivaroxaban, nor dabigatran., Conclusion: Double centrifugation before freezing should remain the recommended pre-analytical condition before TGA., (© 2021 John Wiley & Sons Ltd.)

The hyperproduction of oxidative stress and inflammatory biomarkers, which is paralleled by decreased levels of antioxidant and anti-inflammatory mediators, is part of cellular mechanisms that contribute to the disruption of metabolic homeostasis in obesity. Whether gender-specific alterations and gender-restricted associations in these biomarkers underlie the increased cardiometabolic risk in men compared to women is unclear. We enrolled 31 women and 29 men, aged ≥50 and ≤70 years and with body mass index ≥ 30 and <40 kg/m 2 . We assessed the concentrations of aminothiols (cysteine, homocysteine, and glutathione), expression of oxidant/antioxidant balance, adipomyokines (leptin, adiponectin, myostatin, and interleukin-6), markers of chronic inflammation, and vitamin D, an index of nutritional state, in plasma and serum samples by using HPLC, ELISA, and chemiluminescent immunoassay methods. We measured insulin resistance (IR) by the homeostasis model assessment (HOMA) index. Despite comparable levels of visceral adiposity, IR, and a similar dietary regimen, men showed, with respect to women, higher oxidant concentrations and lower antioxidant levels, which paralleled IR severity. Myostatin levels correlated with prooxidant aminothiols among men only. Gender-specific alterations in aminothiol status and adipomyokine profile and the gender-restricted association between these biomarkers and metabolic derangement are consistent with an increased cardiometabolic risk in men compared to age-matched women with stage I-II obesity. Strict control of redox and inflammatory status, even addressing gender-specific nutritional targets, may be useful to prevent obesity-related metabolic alterations and comorbidities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Jonica Campolo et al.)

Exercise generates reactive oxygen species (ROS), creating a redox imbalance towards oxidation when inadequately intense. Normobaric and hyperbaric oxygen (HBO) breathed while not exercising induces antioxidant enzymes expression, but literature is still poor. Twenty-two athletes were assigned to five groups: controls; 30%, or 50% O 2 ; 100% O 2 (HBO) at 1.5 or 2.5 atmosphere absolute (ATA). Twenty treatments were administered on non-training days. Biological samples were collected at T0 (baseline), T1 (end of treatments), and T2 (1 month after) to assess ROS, antioxidant capacity (TAC), lipid peroxidation, redox (amino-thiols) and inflammatory (IL-6, 10, TNF-α) status, renal function (i.e., neopterin), miRNA, and hemoglobin. At T1, O 2 mixtures and HBO induced an increase of ROS, lipid peroxidation and decreased TAC, counterbalanced at T2. Furthermore, 50% O 2 and HBO treatments determined a reduced state in T2. Neopterin concentration increased at T1 breathing 50% O 2 and HBO at 2.5 ATA. The results suggest that 50% O 2 treatment determined a reduced state in T2; HBO at 1.5 and 2.5 ATA similarly induced protective mechanisms against ROS, despite the latter could expose the body to higher ROS levels and neopterin concentrations. HBO resulted in increased Hb levels and contributed to immunomodulation by regulating interleukin and miRNA expression.

Purpose: This study evaluates among middle-aged subjects with obesity the prevalence of olfactory impairment (OI) with respect to normative values and its correlation with body composition, cognition, sleep quality, and inflammation., Methods: In 60 (31 women, 29 men) volunteers with a body mass index ≥ 30 to ≤ 40 kg/m 2 , aged ≥ 50 to ≤ 70 years, we assessed olfaction by the Sniffin' Stick test. We measured anthropometrics, body composition and metabolic profiles and evaluated cognition by the MiniMental State Examination (MMSE) and sleep disturbances by the Insomnia Severity Index (ISI). Patients were classified into two groups according to a total olfactory score (odor Threshold, Discrimination, Identification, TDI) below or above the 25th percentile from age and gender-adjusted normative data., Results: Overall, 25 subjects (42%) had OI (TDI < 25th percentile). The largest differences between subjects with and without OI were observed in discrimination and identification scores, with a large overlap in olfactory threshold. Subjects with an abnormal TDI showed significantly higher fat mass index, ISI scores and urinary neopterin and lower MMSE scores than those without OI. By multivariable logistic regression, MMSE, ISI score and urinary neopterin were significantly associated to OI., Conclusions: Among middle-aged subjects with stage I and II obesity, OI is highly prevalent and is independently associated with poor self-reported sleep quality, lower cognition scores and higher levels of the inflammatory marker neopterin.

The association between coronavirus disease 2019 (COVID-19) pneumonia and venous thrombotic disorders is still unclear. We assessed the association between COVID-19 infection-related pneumonia and proximal deep-vein thrombosis (DVT) in a cohort of patients admitted to our hospital during the European outbreak in the front line of Cremona, Lombardy. In a single-center cross-sectional study, all patients hospitalized for more than 5 days in Internal Medicine Department with confirmed COVID-19 pneumonia received 2-point compressive ultrasound assessment (CUS) of the leg vein system during a single day. Ninety-four percent of patients received enoxaparin as standard pharmacological prophylaxis for venous thromboembolism. The presence of DVT was defined as incompressibility of popliteal or common femoral vein. Out of 121 patients with COVID-19 pneumonia (mean age 71.8, 66.3% males) hospitalized on March 31st, 70 stayed in hospital for over 5 days and 66 of them underwent CUS of deep venous system of the legs. The presence of asymptomatic DVT was found in 9 patients (13.6%). No symptomatic DVT was found. Patients with DVT showed mean age = 75.7 years, mean D-dimer levels = 4.02 ng/ml and all of them received enoxaparin for thromboprophylaxis, except one. Computed tomography pulmonary angiogram confirmed pulmonary embolism in five patients. One every seven patients with COVID-19-related pneumonia, hospitalized for more than 5 days, had asymptomatic proximal DVT and half of them had confirmed PE despite standard pharmacological thromboprophylaxis. This observational study suggests the need of an active surveillance through CUS in patients hospitalized with acute SARS-COV-2 and underline the need of a more intense thromboprophylaxis.

The effects of two different dietary supplements on the redox status of healthy human participants were evaluated. The first supplement (GluS, Glutathione Synthesis) contains the precursors for the endogenous synthesis of glutathione and the second (GluReS, Glutathione and Resveratrol Synthesis) contains in addition polydatin, a precursor of resveratrol. To assess the influence of GluS and GluReS on the redox status, ten thiol species and three vitamins were measured before (t0) and after 8 weeks (t1) of dietary supplementation. An inflammatory marker, neopterin, was also assessed at the same time points. Both supplements were highly effective in improving the redox status by significantly increasing the reduced-glutathione (GSH) content and other reduced thiol species while significantly decreasing the oxidized species. The positive outcome of the redox status was most significant in the GluRes treatment group which also experienced a significant reduction in neopterin levels. Of note, the endogenous levels of vitamins C, E and A were significantly increased in both treatment groups, with best results in the GluReS group. While both dietary supplements significantly contributed to recognized antioxidant and anti-inflammatory outcomes, the effects of GluReS, the combination of glutathione and resveratrol precursors, were more pronounced. Thus, dietary supplementation with GluReS may represent a valuable strategy for maintaining a competent immune status and a healthy lifespan.

Saturation diving allows divers to reduce the risk of decompression sickness while working at depth for prolonged periods but may increase reactive oxygen species (ROS) production. Such modifications can affect endothelial function by exacerbating oxidative stress. This study investigated the effects of saturation diving on oxidative stress damage. Redox status was evaluated through: ROS production; total antioxidant capacity (TAC); nitric oxide metabolites (NOx); nitrotyrosine (3-NT); and lipid peroxidation (8-iso-PGF2α) assessment. Creatinine and neopterin were analyzed as markers of renal function and damage. Measurements were performed on saliva and urine samples obtained at four time points: pre; deep; post; and 24 h post. Four divers were included in the study. After the saturation dive (post), significant ( p < 0.05) increases in ROS (0.12 ± 0.03 vs. 0.36 ± 0.06 µmol.min -1 ), TAC (1.88 ± 0.03 vs. 2.01 ± 0.08 mM), NOx (207.0 ± 103.3 vs. 441.8 ± 97.3 µM), 3-NT (43.32 ± 18.03 vs. 18.64 ± 7.45 nM·L -1 ), and 8-iso-PGF2α (249.7 ± 45.1 vs. 371.9 ± 54.9 pg·mg -1 creatinine) were detected. Markers of renal damage were increased as well after the end of the saturation dive (creatinine 0.54 ± 0.22 vs. 2.72 ± 1.12 g-L -1 ; neopterin 73.3 ± 27.9 vs. 174.3 ± 20.53 μmol·mol -1 creatinine). These results could ameliorate commercial or military diving protocols or improve the understanding of symptoms caused by oxygen level elevation.

Hyperhomocysteinemia is recognized as risk factor for cardiovascular and age-associated diseases. Folic acid supplementation efficiently lowers plasma homocysteine (Hcy) levels, but high intake may negatively affect health because of unnatural levels of unmetabolized folic acid in the systemic circulation. Oxoproline (Oxo) provides by glutamic acid production an increase of intracellular folic acid trapping. Aim of this study was to compare the efficacy of three supplementation protocols: (1) traditional therapy (5-methyl-tetrahydrofolate: 15 mg/day); (2) 5 mL/day of Oxo with 300 μg folic acid (oxifolic); (3) 5 mL/day of Oxo alone (magnesio+) in a 90 days randomized trial on thirty-two moderate hyperhomocysteinemic (18.6 ± 2.4 μmol.L -1 ) patients (age 48 ± 14 yrs). Thiols: cysteine (Cys), cysteinylglycine (Cys-Gly) and glutathione levels were assessed too. Every supplementation induced significant ( p range <0.05-0.0001) reductions of Hcy level and Cys concentration after the three protocols adopted. Otherwise glutathione concentration significantly increased after oxifolic ( p < 0.01) and traditional ( p < 0.05) supplementation. The integration of Oxo resulted an interesting alternative to traditional therapy because absence or minimal number of folates in the integrator eliminates any chance of excess that can constitute a long-term risk., Competing Interests: The authors declare no conflicts of interest.