Background/Objectives: Mild cognitive impairment (MCI) is accompanied by olfactory dysfunction, and few interventions target shared chemosensory–cognitive mechanisms. We retrospectively examined whether a 5-week oxygen–ozone major autohemotherapy (MAH) cycle is associated with coupled improvements in olfactory and cognitive performance in adults with MCI. Methods: We analyzed 81 individuals with MCI who completed 10 MAH sessions (twice weekly) and 93 matched healthy controls. In the MCI group, olfactory function was measured before and after MAH using Sniffin’ Sticks® threshold–discrimination–identification (TDI) scores; global cognition was assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). We evaluated between-group and pre–post changes and used Spearman correlations to assess olfactory–cognitive coupling. Results: At baseline, MCI participants showed lower TDI and MoCA scores than controls and more hyposmia/anosmia. Following MAH, the proportion of normosmic patients increased from 32.1% to 50.6%, with fewer anosmic cases. TDI scores improved but remained lower than in controls. MMSE scores were unchanged, whereas MoCA total scores increased, with domain-level gains and a significant improvement in Language Repetition. TDI gains were modestly correlated with MoCA total and selected domain changes. Conclusions: In this retrospective cohort, MAH was associated with partial restoration improvements of olfactory function and improved cognitive performance. Correlated olfactory–cognitive changes were observed within the treated MCI group; however, causal attribution to O2–O3 MAH cannot be established without randomized, double-blind, sham-controlled trials with coupled olfactory–cognitive gains consistent with a shared, potentially modifiable substrate. Prospective randomized trials are needed to confirm efficacy and clinical utility.

Obesity is associated with a decrease in chemosensory perception acuity and increased disease risk, pointing to the need for feasible interventions that affect smell, taste, and cardiometabolic markers. Here, subjects with overweight/obesity are treated with six monthly cycles of a fasting-mimicking diet (FMD) lasting 5 days followed by a normal diet for the rest of the month to determine their effects on chemosensory function and cardiometabolic risk factors. Both arms of the 102 randomized cross-over trial participants indicate FMD-dependent improvements in a wide range of taste and smell chemosensory functions. The portion of hyposmic subjects is reduced from 38.1% at baseline to 6.4% at the end of 6 FMD cycles. FMD cycles also reduce cardiometabolic and inflammatory markers and drug use in diabetic patients. This trial provides evidence for the effect of periodic FMD cycles in improving chemosensory function while reducing cardiometabolic risk factors without requiring long-term lifestyle changes. The trial is registered at ClinicalTrials.gov (NCT04529161).

Importance:People who are critically buried by an avalanche typically die of asphyxia within 35 minutes, often making timely rescue impossible. The development of new strategies to delay asphyxiation is crucial to improve survival rates. Objective:To investigate the efficacy of a novel, user-carried avalanche safety device that delivers airflow from avalanche debris to the user's airway without requiring supplemental oxygen or a mouthpiece. Design, Setting, and Participants:This randomized, blinded, clinical trial was organized by 4 institutions and conducted at 1 field location in Italy from January to March 2023. Healthy volunteers aged 18 to 60 years were enrolled. Trial participants underwent a critical snow burial simulation while in a prone position covered by at least 50 cm of snow. Vital parameters were continuously monitored throughout the simulation to ensure participant safety and to collect physiological data. Interventions:Participants were randomized to the safety device group (using the Safeback SBX device) or the control group (using a sham device). The safety device group completed an unblinded control in which the participants who remained buried after 35 minutes were seamlessly transferred to the sham device. Main Outcomes and Measures:The primary outcome measure was the time to oxygen saturation as measured by pulse oximetry (Spo2) less than 80% (event) during 35 minutes of monitoring, comparing intervention and control groups. Secondary outcomes included oxygen and carbon dioxide concentrations at different distances in the snow. Results:Of 36 randomized participants, 24 performed and completed the trial and were included in the final analysis. The median (IQR) age was 27 (25-32) years, and 13 (54%) were male. In the safety device group, the median (IQR) burial duration was 35.0 (35.0-35.0) minutes and there were no events; in the control group, the median (IQR) burial duration was 6.4 (4.8-13.5) minutes and there were 7 events. The safety device group had a significantly lower risk of termination due to Spo2 less than 80% (P < .001 for both log-rank and Breslow tests). Carbon dioxide in the air pocket was 1.3% (95% CI, 1.0%-1.6%) vs 6.1% (95% CI, 5.1%-7.1%) and oxygen was 19.8% (95% CI, 19.5%-20.1%) vs 12.4% (95% CI, 11.2%-13.5%) at the same points in the safety device and control groups, respectively. Conclusions and Relevance:A user-carried avalanche safety device that delivers airflow from avalanche debris to the user's airways without requiring supplemental oxygen delayed critical hypoxemia and hypercapnia during simulated critical burial. Trial Registration:ClinicalTrials.gov Identifier: NCT05779540.

People who are critically buried by an avalanche typically die of asphyxia within 35 minutes, often making timely rescue impossible. The development of new strategies to delay asphyxiation is crucial to improve survival rates. To investigate the efficacy of a novel, user-carried avalanche safety device that delivers airflow from avalanche debris to the user’s airway without requiring supplemental oxygen or a mouthpiece. This randomized, blinded, clinical trial was organized by 4 institutions and conducted at 1 field location in Italy from January to March 2023. Healthy volunteers aged 18 to 60 years were enrolled. Trial participants underwent a critical snow burial simulation while in a prone position covered by at least 50 cm of snow. Vital parameters were continuously monitored throughout the simulation to ensure participant safety and to collect physiological data. Participants were randomized to the safety device group (using the Safeback SBX device) or the control group (using a sham device). The safety device group completed an unblinded control in which the participants who remained buried after 35 minutes were seamlessly transferred to the sham device. The primary outcome measure was the time to oxygen saturation as measured by pulse oximetry (Spo 2 ) less than 80% (event) during 35 minutes of monitoring, comparing intervention and control groups. Secondary outcomes included oxygen and carbon dioxide concentrations at different distances in the snow. Of 36 randomized participants, 24 performed and completed the trial and were included in the final analysis. The median (IQR) age was 27 (25-32) years, and 13 (54%) were male. In the safety device group, the median (IQR) burial duration was 35.0 (35.0-35.0) minutes and there were no events; in the control group, the median (IQR) burial duration was 6.4 (4.8-13.5) minutes and there were 7 events. The safety device group had a significantly lower risk of termination due to Spo 2 less than 80% ( P < .001 for both log-rank and Breslow tests). Carbon dioxide in the air pocket was 1.3% (95% CI, 1.0%-1.6%) vs 6.1% (95% CI, 5.1%-7.1%) and oxygen was 19.8% (95% CI, 19.5%-20.1%) vs 12.4% (95% CI, 11.2%-13.5%) at the same points in the safety device and control groups, respectively. A user-carried avalanche safety device that delivers airflow from avalanche debris to the user’s airways without requiring supplemental oxygen delayed critical hypoxemia and hypercapnia during simulated critical burial. ClinicalTrials.gov Identifier: NCT05779540

OPINION article Front. Endocrinol., 19 January 2024Sec. Obesity Volume 14 - 2023 | https://doi.org/10.3389/fendo.2023.1282276

Differences in gustatory sensitivity, nutritional habits, circulating levels of modulators, anthropometric measures, and metabolic assays may be involved in overweight (OW) development. The present study aimed at evaluating the differences in these aspects between 39 OW (19 female; mean age = 53.51 ± 11.17), 18 stage I (11 female; mean age = 54.3 ± 13.1 years), and 20 II (10 female; mean age = 54.5 ± 11.9) obesity participants when compared with 60 lean subjects (LS; 29 female; mean age = 54.04 ± 10.27). Participants were evaluated based on taste function scores, nutritional habits, levels of modulators (leptin, insulin, ghrelin, and glucose), and bioelectrical impedance analysis measurements. Significant reductions in total and subtests taste scores were found between LS and stage I and II obesity participants. Significant reductions in total and all subtests taste scores were found between OW and stage II obesity participants. Together with the progressive increase in plasmatic leptin levels, insulin, and serum glucose, decrease in plasmatic ghrelin levels, and changes in anthropometric measures and nutritional habits along with body mass index, these data for the first time demonstrated that taste sensitivity, biochemical regulators, and food habits play a parallel, concurring role along the stages evolving to obesity.

Importance Approximately 70% of individuals critically buried in avalanche debris die within 35 minutes as a result of asphyxial cardiac arrest. An artificial air-pocket device (AAPD) that separates inhaled air from exhaled air may delay the onset of severe hypoxemia and eventual asphyxia during snow burial. Objective To investigate the efficacy of a new AAPD during snow burial in a supine position. Design, Setting, and Participants This comparative effectiveness trial was performed in winter 2016 with data analysis in November 2016 and November 2022. Each trial used a simulated critical avalanche burial scenario, in which a trough was dug in a snow pile and an additional air pocket of 0.5 L volume was punched into the lateral wall for each control trial. All participants were buried in a supine position. Trials could be voluntarily terminated at any time, with a maximum length of 60 minutes; trials were automatically terminated if the participant's peripheral oxygen saturation (Spo2) dropped to less than 84%. Exposures Each participant conducted 2 trials, one in which they breathed into the AAPD (intervention trial) and the other in which they breathed into the prepared air pocket (control trial). Main Outcomes and Measures Measurements included Spo2, cerebral oxygenation, ventilatory parameters, respiratory gas concentrations, and visual-analogue scales. Kaplan-Meier survival curves and rank test for matched survival data were used to analyze the total burial time in each trial. Results A total of 13 volunteers (9 men; mean [SD] age, 33 [8] years) were exposed to the intervention and control trials. Intervention trials were terminated less often (2 of 13 trials) as a result of hypoxemia than control trials (11 of 12 trials). Similarly, survival curves showed a longer duration of burial in the intervention compared with the control trials for the time to reach an Spo2 less than 84% (rank test for matched survival data: P = .003). The intervention trials, compared with the control trials, also had slower rates of decrease in fraction of inspired oxygen (mean [SD] rate, -0.8 [0.4] %/min vs -2.2 [1.2] %/min) and of increase in fraction of inspired carbon dioxide (mean [SD] rate, 0.5 [0.3] %/min vs 1.4 [0.6] %/min) and expired ventilation per minute (mean [SD] rate, 0.5 [1.0] L/min2 vs 3.9 [2.6] L/min2). Conclusions and Relevance This comparative effectiveness trial found that the new AAPD was associated with delaying the development of hypoxemia and hypercapnia in supine participants in a critical burial scenario. Use of the AAPD may allow a longer burial time before asphyxial cardiac arrest, which might allow longer times for successful rescue by companions or by prehospital emergency medical services.

Hepatocellular carcinoma (HCC), the most common form of liver cancer, is frequently diagnosed late due to the absence of symptoms during early disease, thus heavily affecting the overall survival of these patients. Soluble immunological factors persistently produced during cirrhosis have been recognized as promoters of chronic inflammation and neoplastic transformation. The aim of this pilot study was to evaluate the predictive value of the cytokine profiles for HCC development. A Luminex xMAP approach was used for the quantification of 45 proteins in plasma and ascitic fluids of 44 cirrhotic patients without or with HCC of different etiologies. The association with patient survival was also evaluated. Univariate analyses revealed that very low levels of interleukin 5 (IL-5) (<15.86 pg/mL) in ascites and IL-15 (<12.40 pg/mL) in plasma were able to predict HCC onset with an accuracy of 81.8% and a sensitivity of 95.2%. Univariate analyses also showed that HCC, hepatitis B virus/hepatitis C virus infections, low levels of IL-5 and granulocyte-macrophage colony-stimulating factor in ascitic fluids, and high levels of eotaxin-1, hepatocyte growth factor and stromal-cell-derived factor 1α in plasma samples were factors potentially associated with a poor prognosis and decreased survival. Our results suggest a potential protective role of some immune modulators that may act in the peritoneal cavity to counteract disease progression leading to HCC development.

To evaluate the changes in gustatory and olfactory sensitivity and dietary habits between healthy lean subjects (LS) and participants affected by overweight (OW), stage I and II obesity and to estimate possible impact of these factors on body mass index (BMI). After a general and ear–nose–throat evaluation, taste and olfactory function testing by means of taste strips and sniffin’ stick tests, respectively, and food habits analysis by means of food frequency questionnaire (FFQ), 221 participants (68 LS [33 female; mean age = 53.01 ± 7.54 years]; 51 OW [26 female; mean age = 51.5 ± 12.16 years]; 50 stage I obesity [24 female; mean age = 50.78 ± 13.71 years] and 52 stage II obesity [24 female; mean age = 52.21 ± 13.35 years]) were enrolled in the study. Significant (p < 0.008) reductions in total and subtest taste and smell scores were found in stage I and II obesity when compared to LS and OW participants. FFQ depicted a progressive intake increase of nutrients along the BMI stages. Significant associations were found between BMI and taste/smell subtests sugar taste carbs, saturated, monounsaturated and polyunsaturated fatty acids. These data demonstrated for the first time a parallel impairment in smell and taste in a large sample size of participants from lean to stage II obesity and could reinforce those previous theories claiming that the greater the ability in taste or smell qualities perception, the lower the preference for them, resulting in a lower intake of specific foods.

Redox homeostasis is a vital process the maintenance of which is assured by the presence of numerous antioxidant small molecules and enzymes and the alteration of which is involved in many pathologies, including several neurodegenerative disorders. Among the different enzymes involved in the antioxidant response, SOD1 and DJ-1 have both been associated with the pathogenesis of amyotrophic lateral sclerosis and Parkinson's disease, suggesting a possible interplay in their mechanism of action. Copper deficiency in the SOD1-active site has been proposed as a central determinant in SOD1-related neurodegeneration. SOD1 maturation mainly relies on the presence of the protein copper chaperone for SOD1 (CCS), but a CCS-independent alternative pathway also exists and functions under anaerobic conditions. To explore the possible involvement of DJ-1 in such a pathway in vivo, we exposed Drosophila melanogaster to anoxia and evaluated the effect of DJ-1 on fly survival and SOD1 levels, in the presence or absence of CCS. Loss of DJ-1 negatively affects the fly response to the anoxic treatment, but our data indicate that the protective activity of DJ-1 is independent of SOD1 in Drosophila, indicating that the two proteins may act in different pathways.

ABSTRACT During recent decades, model organisms such as Drosophila melanogaster have made it possible to study the effects of different environmental oxygen conditions on lifespan and oxidative stress. However, many studies have often yielded controversial results usually assigned to variations in Drosophila genetic background and differences in study design. In this study, we compared longevity and ROS levels in young, unmated males of three laboratory wild-type lines (Canton-S, Oregon-R and Berlin-K) and one mutant line (Sod1n1) as a positive control of redox imbalance, under both normoxic and hypoxic (2% oxygen for 24 h) conditions. Lifespan was used to detect the effects of hypoxic treatment and differences were analysed by means of Kaplan–Meier survival curves and log-rank tests. Electron paramagnetic resonance spectroscopy was used to measure ROS levels and analysis of variance was used to estimate the effects of hypoxic treatment and to assess ROS differences between strains. We observed that the genetic background is a relevant factor involved in D. melanogaster longevity and ROS levels. Indeed, as expected, in normoxia Sod1n1 are the shortest-lived, while the wild-type strains, despite a longer lifespan, show some differences, with the Canton-S line displaying the lowest mortality rate. After hypoxic stress these variances are amplified, with Berlin-K flies showing the highest mortality rate and most evident reduction of lifespan. Moreover, our analysis highlighted differential effects of hypoxia on redox balance/unbalance. Canton-S flies had the lowest increase of ROS level compared to all the other strains, confirming it to be the less sensitive to hypoxic stress. Sod1n1 flies displayed the highest ROS levels in normoxia and after hypoxia. These results should be used to further standardize future Drosophila research models designed to investigate genes and pathways that may be involved in lifespan and/or ROS, as well as comparative studies on specific mutant strains.

EDITORIAL article Front. Physiol., 29 April 2022Sec. Environmental, Aviation and Space Physiology https://doi.org/10.3389/fphys.2022.888005

Objective To evaluate the differences in olfactory sensitivity, nutritional habits, levels of modulators of feeding and smell, bioelectrical impedance analysis (BIA) measures and metabolic assays between two groups of participants with stage I and II obesity and reciprocal relationships between these parameters. Methods Eighteen participants with stage I (11 female; mean age = 54.3 ± 13.1 years) and 20 participants with stage II (10 female; mean age = 54.5 ± 11.9) obesity underwent a food frequency questionnaire and Sniffin' Sticks® test battery, anthropometric parameters, and BIA measurements as well as metabolic assays (including plasma levels of leptin, insulin, ghrelin, glucose, insulin‐like growth factor‐1 [IGF‐1] and usual laboratory parameters). Results The stage II obesity participants demonstrated significant higher levels of insulin and leptin and lower levels of ghrelin and IGF‐1, a reduction in odor identification (OI) and in total olfactory score, and an increase in visceral and total fat percentage. Among a mosaic of multiple correlations, ghrelin was found to positively correlate with OI and leptin negatively with odor discrimination. Conclusion The present study expands the notions positing the olfactory perception – and its connections with metabolic cues, foods habits and BIA measures – changes across the two most important obesity stages. This could ameliorate clinical and research deepening of obesity‐related olfactory behavior with possible consequences on diagnosis, treatment and prevention of onset and development of obesity, thus opening possible future strategies involving multidisciplinary contributions. Level of Evidence 3 Laryngoscope , 132:2028–2035, 2022

Background: A sufficient supply of oxygen is crucial to avoid hypoxic cardiac arrest and brain damage within 30 min in completely-buried avalanche victims. Snow density influences levels of hypoxia and hypercapnia. The goal of this study was to investigate the effects of hypoxia and hypercapnia on cerebral oxygenation (ScO2) in humans breathing into an artificial air pocket. Methods: Each subject breathed into a closed system (air-tight face mask - plastic tube - snow air-pocket of 4 L) up to 30 min. Each subject performed three tests in different snow densities. ScO2 was measured by a near-infrared spectroscopy (NIRS) device. Measurements included peripheral oxygen saturation (SpO(2)), end-tidal carbon dioxide (ETCO2), air pocket gases and blood gases. Snow density was assessed via standard methods and microcomputed tomography. Based on predetermined criteria, tests were classified based on whether they were terminated before 30 min and the reason for termination. The categories were: completed tests (30 min), tests terminated before 30 min when SpO(2) dropped to -75% and tests that were terminated before 30 min by requests of the subjects. General linear models were used to compare termination groups for changes in ScO2, ETCO2, SpO(2) and air pocket gases, and a multivariate analysis was used to detect factor independent effects on ScO2. Results: ScO2 was decreased in the group in which the tests were terminated for SpO(2) - 75% caused by a decrease in oxygen supply in high snow densities. In the completed tests, an increase in ScO2 occurred despite decreased oxygen supply and decreased carbon dioxide removal. Conclusions: Our data show that ScO2 determined by NIRS was not always impaired in humans breathing into an artificial air pocket despite decreased oxygen supply and decreased carbon dioxide removal. This may indicate that in medium to low snow densities brain oxygenation can be sufficient, which may reflect the initial stage of the triple H (hypothermia, hypoxia, and hypercapnia) syndrome. In high snow densities, ScO2 showed a significant decrease caused by a critical decrease in oxygen supply. This could lead to a higher risk of hypoxic cardiac arrest and brain damage.

The aim of the present scoping review was to evaluate the impact of experimental meal loads or observational diet changes/habits on taste tests in both healthy subjects and patients. A systematic search performed in PubMed, Scopus, and Institute for Scientific Information (ISI) Web of Science electronic databases retrieved, respectively 2981, 6258, and 7555 articles from January 2000 to December 2020. A total of 17 articles were included for full-text review. Literature results were stratified according to the observational/interventional approach, the involvement of healthy subjects or patients, the taste test, and the meal/dietary changes. The present scoping review reinforced the notions postulating that certain taste tests (for example focusing on fatty acid, salt, or sugar) might be specifically influenced by the nutritional intervention and that other ones might be susceptible to a wide span of changes beyond the extent of tastant included in the specific food changes. This could also depend on the inhomogeneity of literature trend: The short duration of the intervention or the random type of meal load, unsuitability of the taste test chosen, and the presence of underlying disorders. Future studies for a better comprehension of taste tests reliability in relation to specific food changes are thus to be fostered.

Single-nucleotide polymorphisms (SNPs) in the TERT gene can affect telomere length and TERT expression and have been associated with risk and/or outcome for several tumors, but very few data are available about their impact on rectal cancer. Eight SNPs (rs2736108, rs2735940, rs2736098, rs2736100, rs35241335, rs11742908, rs2736122 and rs2853690), mapping in regulatory and coding regions of the TERT gene, were studied in 194 rectal cancer patients to evaluate their association with constitutive telomere length, circulating TERT mRNA levels, response to neoadjuvant chemoradiotherapy (CRT) and disease outcome. At diagnosis, the rs2736100CC genotype was associated with longer telomeres measured pre-CRT, while the rs2736100CC, rs2736108TT and rs2735940AA were associated with greater telomere erosion evaluated post-CRT. The rs2736108CC and rs2853690AA/GG genotypes, respectively associated with lower telomere erosion and lower levels of circulating TERT post-CRT, were also independently associated with a better response to therapy [OR 4.6(1.1–19.1) and 3.0(1.3–6.9)]. Overall, post-CRT, low levels (≤ median value) of circulating TERT and its stable/decreasing levels compared to those pre-CRT, were independently associated with a better response to therapy [OR 5.8(1.9–17.8) and 5.3(1.4–19.4), respectively]. Furthermore, post-CRT, patients with long telomeres (>median value) and low levels of circulating TERT had a significantly lower risk of disease progression [HR 0.4(0.1–0.9) and 0.3(0.1–0.8), respectively]. These findings suggest that TERT SNPs could be a useful tool for improving the selection of patients who could benefit from CRT and support the role of telomere length and circulating TERT mRNA levels as useful markers for monitoring the response to therapy and disease outcome in rectal cancer patients.

Aim: Clinical features of esophageal cancer (EC) patients have poor prognostic power. Thus, it is paramount to discover biomarkers that can allow a more accurate survival prediction. Methods: To detect genetic variants associated with survival, DNA from 120 patients treated with cisplatin-based neoadjuvant therapy were genotyped using drug metabolism enzymes and transporters array. Results: We identified two variants: the rs2038067 in PPARD (p = 0.0004) and the rs683369 (F160L) in SLC22A1 (p = 0.001). Their prognostic power was greater than that of clinical stage alone (p = 0.017) and comparable to that of response to neoadjuvant therapy (p = 0.71). Interestingly, the prognostic accuracy of response models increased significantly when genetic variables were included (p = 0.003). Conclusion: Our data, though preliminary, strengthen the potential utility of germline variants for a better-tailored management of EC patients.

High altitude is a natural laboratory, within which the clinical study of human physiological response to hypobaric hypoxia (HH) is possible. Failure in the response results in progressive hypoxemia, inflammation and increased tissue oxidative stress (OxS). Thus, investigating temporal changes in key transcription factors (TFs) HIF-1α, HIF-2α, NF-κB and NRF2 mRNA levels, relative to OxS and inflammatory markers, may reveal molecular targets which contrast deleterious effects of hypoxia. Biological samples and clinical data from 15 healthy participants were collected at baseline and after rapid, passive ascent to 3830 m (24 h and 72 h). Gene expression was assessed by qPCR and ROS generation was determined by EPR spectroscopy. Oxidative damage and cytokine levels were estimated by immuno or enzymatic methods. Hypoxia transiently enhanced HIF-1α mRNA levels over time reaching a peak after 24 h. Whereas, HIF-2α and NRF2 mRNA levels increased over time. In contrast, the NF-κB mRNA levels remained unchanged. Plasma levels of IL-1β and IL-6 also remained within normal ranges. ROS production rate and markers of OxS damage were significantly increased over time. The analysis of TF-gene expression suggests that HIF-1α is a lead TF during sub-acute HH exposure. The prolongation of the HH exposure led to a switch between HIF-1α and HIF-2α/NRF2, suggesting the activation of new pathways. These results provide new insights regarding the temporal regulation of TFs, inflammatory state, and ROS homeostasis involved in human hypoxic response, potentially also relevant to the mediation of diseases that induce a hypoxic state.

Breath-hold diving results in significant changes in blood gases’ levels. Challenging variations in oxygen partial pressures may induce reactive oxygen species (ROS) production that exacerbate oxidative stress and, consequently, affect endothelial function. The aim of this study was to investigate the effects of breath-hold diving on oxidative stress damage, assessing ROS production. Nitric oxide metabolites, inducible nitric oxide synthase (iNOS), aminothiols, and renal function were evaluated too as markers of redox status and renal damage. ROS production was assessed with electron paramagnetic resonance. Oxidative status values were measured at pre- and post-40 m dive in a deep swimming pool (Y-40) from six divers (mean age 46.6 ± 9.3 years; height 176 ± 4 cm; BMI 25 ± 2.9 kg/m2). Significant (p < 0.05) increases at post-dive of ROS production rate (0.158 ± 0.003 vs 0.195 ± 0.006 μmol min−1), lipid peroxidation (8-isoprostane: 375.67 ± 195.62 vs 420.49 ± 232.31 pg mg−1 creatinine), nitrate (27.91 ± 19.71 vs 30.80 ± 20.44 μM), iNOS (31.30 ± 4.52 vs 35.68 ± 6.72 IU mL−1) and neopterin concentration (96.20 ± 40.41 vs 118.76 ± 27.84 μmol mol−1 creatinine) were recorded. Conversely, the antioxidant capacity significantly decreased (3.423 ± 0.089 vs 3.015 ± 0.284 mM) after immersion. Overproduction of ROS and consequent oxidative damage to lipids of membrane and antioxidant capacity decreasing reflect also a hypoxic condition, which in the breath-hold diving typically occurs in the last few meters below the surface. iNOS produces NO in large quantities under the examined extreme conditions. Neopterin and creatinine concentration level increased, suggesting an “impairment of renal function” as a likely physiological response to PaO2 variations during dive activity.

Esophageal cancer (EC) is a very aggressive tumor, and no reliable prognostic markers exist especially for resectable advanced neoplasia. The principal aim of this study was to investigate the association of germline polymorphisms in nucleotide excision repair (NER) pathway genes with the overall survival (OS) of patients with advanced EC. As a second aim, we also studied the association of NER gene variants with response to cisplatin-based chemotherapy. Among the EC patients referred to our Institution between 2004 and 2012, we selected a cohort of 180 patients diagnosed with a clinical tumor stage ranging from IIB and IVA. Patients were genotyped for four NER variants, two in the ERCC1 (rs11615 and rs3212986) and two in the ERCC2/XPD (rs1799793 and rs13181) genes. Kaplan-Meier analyses and Cox proportional hazards model were used to evaluate the associations of the selected variants with OS; association with response to neoadjuvant therapy was investigated using logistic regression. Results showed that the ERCC1 rs3212986 and the ERCC2/XPD rs1799793 were significantly associated with shorter OS. On the contrary, response association analysis displayed that, while rs11615 and rs3212986 in ERCC1 were associated with response, both ERCC2/XPD variants were not. By creating survival prediction models, we showed that the rs3212986 and the rs1799793 have a better predictability of the tumor stage alone. Furthermore, they were able to improve the power of the clinical model (AUC = 0.660 vs. AUC = 0.548, p = 0.004). In conclusion, our results indicate that the ERCC1 rs3212986 and the ERCC2/XPD rs1799793 could be used as surrogate markers for a better stratification of EC patients with advanced resectable tumor.