Oxidative stress-related cellular aging causes dysfunction of the Kv3.1/KCNC1 channel reverted by melatonin.

The voltage-gated Kv3.1/KCNC1 channel is abundantly expressed in fast-spiking principal neurons and GABAergic inhibitory interneurons throughout the ascending auditory pathway and in various brain regions. Inactivating mutations in the KCNC1 gene lead to forms of epilepsy and a decline in the expression of the Kv3.1 channel is involved in age-related hearing loss. As oxidative stress plays a fundamental role in the pathogenesis of epilepsy and age-related hearing loss, we hypothesized that an oxidative insult might affect the function of this channel. To verify this hypothesis, the activity and expression of endogenous and ectopic Kv3.1 were measured in models of oxidative stress-related aging represented by cell lines exposed to 100 mM d-galactose. In these models, intracellular reactive oxygen species, thiobarbituric acid reactive substances, sulfhydryl groups of cellular proteins, and the activity of catalase and superoxide dismutase were dysregulated, while the current density of Kv3.1 was significantly reduced. Importantly, the antioxidant melatonin reverted all these effects. The reduction of function of Kv3.1 was not determined by direct oxidation of amino acid side chains of the protein channel or reduction of transcript or total protein levels but was linked to reduced trafficking to the cell surface associated with Src phosphorylation as well as metabolic and endoplasmic reticulum stress. The data presented here specify Kv3.1 as a novel target of oxidative stress and suggest that Kv3.1 dysfunction might contribute to age-related hearing loss and increased prevalence of epilepsy during aging. The pharmacological use of the antioxidant melatonin can be protective in this setting.

Markers of sensory dynamics in phenols-rich virgin olive oils under optimal storage conditions.

Early changes in sensory quality of phenols-rich virgin olive oil (VOO) and their relationship with the chemical changes are less studied in the literature. Therefore, the objective of this study was to propose a predictive model of dynamics of sensory changes based on specific chemical markers. The evolution of the sensory quality of phenol-rich VOOs from Tuscan cultivars stored under optimal storage conditions (i.e., absence of light, no O2 exposure, low temperature) was investigated using a multi-step methodological approach combining sensory (official sensory analysis (so-called Panel Test), Descriptive Analysis and Temporal Dominance of Sensation) and chemical measurements. The sensory map from descriptive data was related to the phenolic and volatile profiles, measured using HPLC-DAD and HS-SPME-GC-MS, respectively. A predictive model of the sensory changes over storage based on chemical compounds was developed. Results showed that very early changes involving phenolic and volatile compounds profiles occur in VOOs stored under optimal storage conditions, which turn in changes in sensory properties evaluated by the official panel test, the descriptive analysis and the temporal dominance of sensation. Furthermore, a chemical marker of sensory dynamics of oils during storage was identified as the ratio between two groups of secoiridoids. The proposed model, supported by the mentioned chemical marker, has the potential of improving the control of sensory changes in phenols-rich virgin olive oils during storage in optimal conditions.

Distinct Sensory Hedonic Functions for Sourness in Adults.

Over the last half-century, variable responses to sweetness have repeatedly been shown to fall into a small number of hedonic responses, implying that looking only at group means may can obfuscate meaningfully different response patterns. Comparative data for sourness is quite sparse, especially in adults. While increased liking with higher acid concentration has been reported for some children, in adults, sourness is classically assumed to be aversive, with a monotonic drop in liking with increasing sourness. Here, we test this assumption using a simple model system or experimental beverage in convenience samples of adults from the United States (increasing citric acid in water) and Italy (increasing citric acid in pear juice). Participants rated intensity and liking of sampled stimuli. For both cohorts, we find clear evidence of three distinct patterns of responses: a strong negative group where liking dropped with increased sourness, an intermediate group who showed a more muted drop in liking with more sourness, and a strong positive group where liking increased with more sourness. Strikingly, both cohorts showed similar proportions of response patterns, with ~63-70% in the strong negative group, and 11-12% in the strong positive group, suggesting these proportions may be stable across cultures. Notably, the three groups did not differ by age or gender. These data support the existence of different hedonic response profiles to sour stimuli in adults, once again highlighting the importance of looking at individual differences and potential consumer segments, rather than merely averaging hedonic responses across all individuals within a group.

Interventions based on sensory-hedonic strategies and on nudging to facilitate vegetable and pulses consumption in the school environment.

Childhood and adolescence shape lifelong taste preferences and dietary habits, making them crucial periods for promoting healthy and sustainable eating. As students consume up to half of their daily energy intake at school, school interventions can have a significant impact on promoting plant-based diets. Although the benefits of promoting plant-based diets on children's and adolescents' health and environmental sustainability are well established and various studies report promising effects of interventions based on sensory-hedonic strategies and on nudging in promoting vegetables and pulses in schools, a comprehensive collection of those reports is lacking. Therefore, this systematic review aims to collect published literature on the above interventions in schools that focus on promoting the consumption of vegetables and pulses to children and adolescents. Three databases-PubMed, Scopus, and Web of Science-were searched over all years until March 2022 using pre-specified terms. From the 10.488 studies identified, a total of 57 studies reporting sensory-hedonic (e.g., manipulating food sensory properties or their hedonic value) or nudging (e.g., changing the presentation) interventions targeting children and/or adolescents in schools and aiming at promoting vegetables and/or pulses were included. Overall, interventions based on sensory-hedonic strategies (either enhancing the perception of well-accepted flavor and texture or manipulating their hedonic value) and on nudging (through incentives and prompts) are effective in promoting vegetables and pulses. A gap in the literature was identified for interventions targeting adolescents and promoting pulses. Finally, multicomponent interventions, rather than using one strategy alone, could be more successful.

Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?

(1) Background: Few data are available on the risk of airway dysfunction in protease inhibitor (PI*) M heterozygotes carrying rare null or deficient allelic variants of the gene SERPINA-1 (PI*MR). (2) Methods: In this observational study, in a cohort of PI*MR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PI*MZ and PI*MS patients. (3) Results: A total of 60 patients were recruited; 35 PI*MR, 11 PI*MZ and 14 PI*MS. At the annual follow-up, the PI*MR and PI*MZ patients demonstrated a significantly higher FEV1 decline than the PI*MS group (p = 0.04 and p = 0.018, respectively). The PI*MR patients showed a significant increase in DLCO annual decline in comparison with the PI*MS group (p = 0.02). At baseline, the PI*MR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV1, FEV1/FVC and DLCO (p = 0.0004, p < 0.0001, p = 0.007, respectively) and, at the one-year follow-up, they displayed a significantly higher FEV1 and DLCO decline (p = 0.0022, p = 0.011, respectively). PI*MR heterozygotes with COPD showed a significantly higher FEV1, FEV1/FVC and DLCO annual decline in comparison with healthy PI*MR (p = 0.0083, p = 0.043, p = 0.041). (4) Conclusions: These results suggest that PI*MR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored.

Melatonin protects Kir2.1 function in an oxidative stress-related model of aging neuroglia.

Melatonin is a pleiotropic biofactor and an effective antioxidant and free radical scavenger and, as such, can be protective in oxidative stress-related brain conditions including epilepsy and aging. To test the potential protective effect of melatonin on brain homeostasis and identify the corresponding molecular targets, we established a new model of oxidative stress-related aging neuroglia represented by U-87 MG cells exposed to D-galactose (D-Gal). This model was characterized by a substantial elevation of markers of oxidative stress, lipid peroxidation, and protein oxidation. The function of the inward rectifying K+ channel Kir2.1, which was identified as the main Kir channel endogenously expressed in these cells, was dramatically impaired. Kir2.1 was unlikely a direct target of oxidative stress, but the loss of function resulted from a reduction of protein abundance, with no alterations in transcript levels and trafficking to the cell surface. Importantly, melatonin reverted these changes. All findings, including the melatonin antioxidant effect, were reproduced in heterologous expression systems. We conclude that the glial Kir2.1 can be a target of oxidative stress and further suggest that inhibition of its function might alter the extracellular K+ buffering in the brain, therefore contributing to neuronal hyperexcitability and epileptogenesis during aging. Melatonin can play a protective role in this context.

AAPH-induced oxidative damage reduced anion exchanger 1 (SLC4A1/AE1) activity in human red blood cells: protective effect of an anthocyanin-rich extract.

Introduction: During their lifespan in the bloodstream, red blood cells (RBCs) are exposed to multiple stressors, including increased oxidative stress, which can affect their morphology and function, thereby contributing to disease. Aim: This investigation aimed to explore the cellular and molecular mechanisms related to oxidative stress underlying anion exchanger 1 activity (band 3, SLC4A1/AE1) in human RBCs. To achieve this aim, the relationship between RBC morphology and functional and metabolic activity has been explored. Moreover, the potential protective effect of an anthocyanin-enriched fraction extracted from Callistemon citrinus flowers was studied. Methods: Cellular morphology, parameters of oxidative stress, as well as the anion exchange capability of band 3 have been analyzed in RBCs treated for 1 h with 50 mM of the pro-oxidant 2,2'-azobis (2-methylpropionamide)-dihydrochloride (AAPH). Before or after the oxidative insult, subsets of cells were exposed to 0.01 µg/mL of an anthocyanin-enriched fraction for 1 h. Results: Exposure to AAPH caused oxidative stress, exhaustion of reduced glutathione, and over-activation of the endogenous antioxidant machinery, resulting in morphological alterations of RBCs, specifically the formation of acanthocytes, increased lipid peroxidation and oxidation of proteins, as well as abnormal distribution and hyper-phosphorylation of band 3. Expected, oxidative stress was also associated with a decreased band 3 ion transport activity and an increase of oxidized haemoglobin, which led to abnormal clustering of band 3. Exposure of cells to the anthocyanin-enriched fraction prior to, but not after, oxidative stress efficiently counteracted oxidative stress-related alterations. Importantly, protection of band3 function from oxidative stress could only be achieved in intact cells and not in RBC ghosts. Conclusion: These findings contribute a) to clarify oxidative stress-related physiological and biochemical alterations in human RBCs, b) propose anthocyanins as natural antioxidants to neutralize oxidative stress-related modifications, and 3) suggest that cell integrity, and therefore a cytosolic component, is required to reverse oxidative stress-related pathophysiological derangements in human mature RBCs.

Bringing down barriers to children's healthy eating: a critical review of opportunities, within a complex food system.

This narrative review revises the scientific evidence of recent years on healthy eating in children and adolescents, making sense of promising avenues of action, from a food system perspective. A conceptual framework is provided to better understand how eating habits of children and adolescents are shaped to identify key multisectoral approaches that should be implemented to promote healthier diets. The following influencing factors are discussed: individual factors (physiological and psychological factors, food preferences and food literacy competencies), factors within the personal and socio-cultural food environments, external food environments, and the supply chain. In each section, the main barriers to healthy eating are briefly discussed focussing on how to overcome them. Finally, a discussion with recommendations of actions is provided, anchored in scientific knowledge, and transferable to the general public, industry, and policymakers. We highlight that multidisciplinary approaches are not enough, a systems approach, with a truly holistic view, is needed. Apart from introducing systemic changes, a variety of interventions can be implemented at different levels to foster healthier diets in children through fostering healthier and more sustainable food environments, facilitating pleasurable sensory experiences, increasing their food literacy, and enhancing their agency by empowering them to make better food related decisions. Acknowledging children as unique individuals is required, through interpersonal interactions, as well as their role in their environments. Actions should aim to enable children and adolescents as active participants within sustainable food systems, to support healthier dietary behaviours that can be sustained throughout life, impacting health at a societal level.

Mechanisms underlying the anti-aging activity of bergamot (Citrus bergamia) extract in human red blood cells.

Introduction: Aging is a process characterised by a decline in physiological functions. Reactive species play a crucial role in the aging rate. Due to the close relationship between aging and oxidative stress, functional foods rich in phytochemicals are excellent candidates to neutralise age-related changes. Aim: This investigation aims to verify the potential protective role of bergamot (Citrus bergamia, Femminello cultivar) peel and juice extract in a model of aging represented by human red blood cells (RBCs) exposed to D-Galactose (DGal). Methods: Bergamot peel and juice extracts were subjected to RP-HPLC/PDA/MS for determination of their composition in bioactive compounds. Markers of oxidative stress, including ROS production, thiobarbituric acid reactive substances (TBARS) levels -a marker of lipid peroxidation, oxidation of total protein sulfhydryl groups, as well as the expression and anion exchange capability of band 3 and glycated haemoglobin (A1c) production have been investigated in RBCs treated with D-Gal for 24 h, with or without pre-incubation for 15 min with 5 µg/mL peel or juice extract. In addition, the activity of the endogenous antioxidant system, including catalase (CAT) and superoxide dismutase (SOD), as well as the diversion of the RBC metabolism from glycolysis towards the pentose phosphate pathway shunt, as denoted by activation of glucose-6-phosphate dehydrogenase (G6PDH), have been explored. Results: Data shown here suggest that bergamot peel and juice extract i) prevented the D-Gal-induced ROS production, and consequently, oxidative stress injury to biological macromolecules including membrane lipids and proteins; ii) significantly restored D-Gal-induced alterations in the distribution and ion transport kinetics of band 3; iii) blunted A1c production; iv) effectively impeded the over-activation of the endogenous antioxidant enzymes CAT and SOD; and v) significantly prevented the activation of G6PDH. Discussion: These results further contribute to shed light on aging mechanisms in human RBCs and identify bergamot as a functional food rich in natural antioxidants useful for prevention and treatment of oxidative stress-related changes, which may lead to pathological states during aging.

Aging Injury Impairs Structural Properties and Cell Signaling in Human Red Blood Cells; Açaì Berry Is a Keystone.

Red blood cell (RBC) deformability is the ability of cells to modulate their shape to ensure transit through narrow capillaries of the microcirculation. A loss of deformability can occur in several pathological conditions, during natural RBC aging through an increase in membrane protein phosphorylation, and/or through the structural rearrangements of cytoskeletal proteins due to oxidative conditions, with a key role played by band 3. Due to the close relationship between aging and oxidative stress, flavonoid-rich foods are good candidates to counteract age-related alterations. This study aims to verify the beneficial role of Açaì extract in a d-Galactose (d-Gal)-induced model of aging in human RBCs. To this end, band 3 phosphorylation and structural rearrangements in membrane cytoskeleton-associated proteins, namely spectrin, ankyrin, and/or protein 4.1, are analyzed in RBCs treated with 100 mM d-Gal for 24 h, with or without pre-incubation with 10 µg/mL Açaì extract for 1 h. Furthermore, RBC deformability is also measured. Tyrosine phosphorylation of band 3, membrane cytoskeleton-associated proteins, and RBC deformability (elongation index) are analyzed using western blotting analysis, FACScan flow cytometry, and ektacytometry, respectively. The present data show that: (i) Açaì berry extract restores the increase in band 3 tyrosine phosphorylation and Syk kinase levels after exposure to 100 mM d-Gal treatment; and (ii) Açaì berry extract partially restores alterations in the distribution of spectrin, ankyrin, and protein 4.1. Interestingly, the significant decrease in membrane RBC deformability associated with d-Gal treatment is alleviated by pre-treatment with Açaì extract. These findings further contribute to clarify mechanisms of natural aging in human RBCs, and propose flavonoid substances as potential natural antioxidants for the treatment and/or prevention of oxidative-stress-related disease risk.

Mercury Chloride Affects Band 3 Protein-Mediated Anionic Transport in Red Blood Cells: Role of Oxidative Stress and Protective Effect of Olive Oil Polyphenols.

Mercury is a toxic heavy metal widely dispersed in the natural environment. Mercury exposure induces an increase in oxidative stress in red blood cells (RBCs) through the production of reactive species and alteration of the endogenous antioxidant defense system. Recently, among various natural antioxidants, the polyphenols from extra-virgin olive oil (EVOO), an important element of the Mediterranean diet, have generated growing interest. Here, we examined the potential protective effects of hydroxytyrosol (HT) and/or homovanillyl alcohol (HVA) on an oxidative stress model represented by human RBCs treated with HgCl2 (10 µM, 4 h of incubation). Morphological changes as well as markers of oxidative stress, including thiobarbituric acid reactive substance (TBARS) levels, the oxidation of protein sulfhydryl (-SH) groups, methemoglobin formation (% MetHb), apoptotic cells, a reduced glutathione/oxidized glutathione ratio, Band 3 protein (B3p) content, and anion exchange capability through B3p were analyzed in RBCs treated with HgCl2 with or without 10 µM HT and/or HVA pre-treatment for 15 min. Our data show that 10 µM HT and/or HVA pre-incubation impaired both acanthocytes formation, due to 10 µM HgCl2, and mercury-induced oxidative stress injury and, moreover, restored the endogenous antioxidant system. Interestingly, HgCl2 treatment was associated with a decrease in the rate constant for SO42- uptake through B3p as well as MetHb formation. Both alterations were attenuated by pre-treatment with HT and/or HVA. These findings provide mechanistic insights into benefits deriving from the use of naturally occurring polyphenols against oxidative stress induced by HgCl2 on RBCs. Thus, dietary supplementation with polyphenols might be useful in populations exposed to HgCl2 poisoning.

Oxidative Stress and Immune Response in Melanoma: Ion Channels as Targets of Therapy.

Oxidative stress and immune response play an important role in the development of several cancers, including melanoma. Ion channels are aberrantly expressed in tumour cells and regulate neoplastic transformation, malignant progression, and resistance to therapy. Ion channels are localized in the plasma membrane or other cellular membranes and are targets of oxidative stress, which is particularly elevated in melanoma. At the same time, ion channels are crucial for normal and cancer cell physiology and are subject to multiple layers of regulation, and therefore represent promising targets for therapeutic intervention. In this review, we analyzed the effects of oxidative stress on ion channels on a molecular and cellular level and in the context of melanoma progression and immune evasion. The possible role of ion channels as targets of alternative therapeutic strategies in melanoma was discussed.

Factors affecting stated liking for meat products: Focus on demographics, oral responsiveness, personality, and psycho-attitudinal traits.

Demographics, anthropometrics, oral responsiveness to sensory stimuli and psycho-attitudinal traits were collected from a representative Italian population sample (n = 2384; 58% women, age 18-60 years) and considered as possible explanatory variables affecting meat liking. Differences in motives underlying individual variation in liking for meat were independently investigated by gender. Three groups of subjects were identified based on liking ratings: Slightly Likers, Likers and Lovers. Both common and gender-specific variables affecting liking for meat were identified. The interest in food (including its rewarding function) and eating experience, low food neophobia and relatively high Body Mass Index characterized meat Lovers irrespective to gender. The careful food selection and the food comforting function further characterized women meat Lovers. Men Slightly Likers were characterized by the interest for health-related food aspects, importance assigned to naturalness and restrained eating. Markers of oral responsiveness were ineffective for describing variation in liking for meat.

Antioxidant Activity of Quercetin in a H2O2-Induced Oxidative Stress Model in Red Blood Cells: Functional Role of Band 3 Protein.

During their lifespan, red blood cells (RBCs) are exposed to a large number of stressors and are therefore considered as a suitable model to investigate cell response to oxidative stress (OS). This study was conducted to evaluate the potential beneficial effects of the natural antioxidant quercetin (Q) on an OS model represented by human RBCs treated with H2O2. Markers of OS, including % hemolysis, reactive oxygen species (ROS) production, thiobarbituric acid reactive substances (TBARS) levels, oxidation of protein sulfhydryl groups, CD47 and B3p expression, methemoglobin formation (% MetHb), as well as the anion exchange capability through Band 3 protein (B3p) have been analyzed in RBCs treated for 1 h with 20 mM H2O2 with or without pre-treatment for 1 h with 10 µM Q, or in RBCs pre-treated with 20 mM H2O2 and then exposed to 10 µM Q. The results show that pre-treatment with Q is more effective than post-treatment to counteract OS in RBCs. In particular, pre-exposure to Q avoided morphological alterations (formation of acanthocytes), prevented H2O2-induced OS damage, and restored the abnormal distribution of B3p and CD47 expression. Moreover, H2O2 exposure was associated with a decreased rate constant of SO42- uptake via B3p, as well as an increased MetHb formation. Both alterations have been attenuated by pre-treatment with 10 µM Q. These results contribute (1) to elucidate OS-related events in human RBCs, (2) propose Q as natural antioxidant to counteract OS-related alterations, and (3) identify B3p as a possible target for the treatment and prevention of OS-related disease conditions or aging-related complications impacting on RBCs physiology.

Açaì (Euterpe oleracea) Extract Protects Human Erythrocytes from Age-Related Oxidative Stress.

Aging is a process characterised by a general decline in physiological functions. The high bioavailability of reactive oxygen species (ROS) plays an important role in the aging rate. Due to the close relationship between aging and oxidative stress (OS), functional foods rich in flavonoids are excellent candidates to counteract age-related changes. This study aimed to verify the protective role of Açaì extract in a d-Galactose (d-Gal)-induced model of aging in human erythrocytes. Markers of OS, including ROS production, thiobarbituric acid reactive substances (TBARS) levels, oxidation of protein sulfhydryl groups, as well as the anion exchange capability through Band 3 protein (B3p) and glycated haemoglobin (A1c) have been analysed in erythrocytes treated with d-Gal for 24 h, with or without pre-incubation for 1 h with 0.5-10 µg/mL Açaì extract. Our results show that the extract avoided the formation of acanthocytes and leptocytes observed after exposure to 50 and 100 mM d-Gal, respectively, prevented d-Gal-induced OS damage, and restored alterations in the distribution of B3p and CD47 proteins. Interestingly, d-Gal exposure was associated with an acceleration of the rate constant of SO42- uptake through B3p, as well as A1c formation. Both alterations have been attenuated by pre-treatment with the Açaì extract. These findings contribute to clarify the aging mechanisms in human erythrocytes and propose functional foods rich in flavonoids as natural antioxidants for the treatment and prevention of OS-related disease conditions.

Correction: Endrizzi et al. Relationships between Intensity and Liking for Chemosensory Stimuli in Food Models: A Large-Scale Consumer Segmentation. Foods 2022, 11, 5.

In the original publication [1], there was a mistake in "Figure 2, Figure 3, Figure 4, and Figure 5" as published [...].

Oxidation Stress as a Mechanism of Aging in Human Erythrocytes: Protective Effect of Quercetin.

Aging is a multi-factorial process developing through a complex net of interactions between biological and cellular mechanisms and it involves oxidative stress (OS) as well as protein glycation. The aim of the present work was to verify the protective role of Quercetin (Q), a polyphenolic flavonoid compound, in a d-Galactose (d-Gal)-induced model of aging in human erythrocytes. The anion-exchange capability through the Band 3 protein (B3p) measured by the rate constant of the SO42- uptake, thiobarbituric acid reactive substances (TBARS) levels-a marker of lipid peroxidation-total sulfhydryl (-SH) groups, glycated hemoglobin (A1c), and a reduced glutathione/oxidized glutathione (GSH-GSSG) ratio were determined following the exposure of erythrocytes to 100 mM d-Gal for 24 h, with or without pre-incubation with 10 µM Q. The results confirmed that d-Gal activated OS pathways in human erythrocytes, affecting both membrane lipids and proteins, as denoted by increased TBARS levels and decreased total sulfhydryl groups, respectively. In addition, d-Gal led to an acceleration of the rate constant of the SO42- uptake through the B3p. Both the alteration of the B3p function and oxidative damage have been improved by pre-treatment with Q, which preferentially ameliorated lipid peroxidation rather than protein oxidation. Moreover, Q prevented glycated A1c formation, while no protective effect on the endogenous antioxidant system (GSH-GSSG) was observed. These findings suggest that the B3p could be a novel potential target of antioxidant treatments to counteract aging-related disturbances. Further studies are needed to confirm the possible role of Q in pharmacological strategies against aging.

Versatility of Intermittent Abdominal Pressure Ventilation in a Case of Complicated Restrictive Respiratory Failure and COVID-19.

BACKGROUND: The intermittent abdominal pressure ventilation (IAPV) is a non-invasive ventilation (NIV) technique that avoids facial interfaces and is a diurnal ventilatory support alternative for neuromuscular patients during stable chronic phases of the disease. Coronavirus disease 2019 (COVID-19) is a novel infection possibly causing acute respiratory distress syndrome (ARDS). Neuromuscular diseases (NMD) and preexisting respiratory failure can be exacerbated by respiratory infection and progress to severe disease and ICU admission with a poor prognosis. AIM: To report on the versatility and feasibility of IAPV in acute restrictive respiratory failure exacerbated by COVID-19. PATIENT: We describe the case of a 33-year-old man with spastic tetraparesis, kyphoscoliosis, and impaired cough, eventually leading to a restrictive ventilation pattern. COVID-19 exacerbated respiratory failure and seizures. An NIV trial failed because of inadequate interface adhesion and intolerance. During NIV, dyspnea and seizures worsened. He underwent a high flow nasal cannula (HFNC) with a fluctuating benefit on gas exchange. IAPV was initiated and although there was a lack of cooperation and inability to sit; the compliance was good and a progressive improvement of gas exchange, respiratory rate, and dyspnea was observed. CONCLUSIONS: IAPV is a versatile type of NIV that can be adopted in complicated restrictive respiratory failure. COVID-19 exacerbates preexisting conditions and is destined to be a disease of frailty. COVID-19 is not a contraindication to IAPV and this kind of ventilation can be employed in selected cases in a specialistic setting. Moreover, this report suggests that IAPV is safe when used in combination with HFNC. This hybrid approach provides the opportunity to benefit from both therapies, and, in this particular case, prevented the intubation with all connected risks.

An olfactory self-test effectively screens for COVID-19.

Background: Key to curtailing the COVID-19 pandemic are wide-scale screening strategies. An ideal screen is one that would not rely on transporting, distributing, and collecting physical specimens. Given the olfactory impairment associated with COVID-19, we developed a perceptual measure of olfaction that relies on smelling household odorants and rating them online. Methods: Each participant was instructed to select 5 household items, and rate their perceived odor pleasantness and intensity using an online visual analogue scale. We used this data to assign an olfactory perceptual fingerprint, a value that reflects the perceived difference between odorants. We tested the performance of this real-time tool in a total of 13,484 participants (462 COVID-19 positive) from 134 countries who provided 178,820 perceptual ratings of 60 different household odorants. Results: We observe that olfactory ratings are indicative of COVID-19 status in a country, significantly correlating with national infection rates over time. More importantly, we observe indicative power at the individual level (79% sensitivity and 87% specificity). Critically, this olfactory screen remains effective in participants with COVID-19 but without symptoms, and in participants with symptoms but without COVID-19. Conclusions: The current odorant-based olfactory screen adds a component to online symptom-checkers, to potentially provide an added first line of defense that can help fight disease progression at the population level. The data derived from this tool may allow better understanding of the link between COVID-19 and olfaction.

Exploring the association between oral tactile sensitivity measures and phenotypic markers of oral responsiveness.

This study investigated the individual variability in oral tactile sensitivity considering touch, by means of Von Frey Hair monofilaments (VFH) and spatial resolution, using the grating orientation test (GOT). The relationships of the two measures with 6-n-propylthiouracil (PROP) responsiveness and fungiform papillae density and size were investigated. One hundred and forty-four subjects (48.6% women, aged 18-30) participated in the study. VFH and GOT thresholds were assessed by three-down/one-up staircase method. Responsiveness to 3.2 mM PROP was assessed on the general Labeled Magnitude Scale. Fungiform papillae density (FPD) and size were determined from automated counting. VFH thresholds appeared unsuitable to reveal individual variation in responsiveness to point-pressure on the tongue. The frequency of GOT thresholds approximated a normal distribution and covered the whole range of variation, thus indicating an ability to measure individual variation in oral tactile sensitivity. No significant linear correlations were found between any of the oral tactile sensitivity measures and PROP responsiveness, FPD total and size class. VFH and GOT thresholds were not significantly associated. Agglomerative hierarchical clustering was used to classify participants for their PROP responsiveness, total FPD and GOT threshold. Three clusters were identified, C1 (n = 67), Cl2 (n = 42), and Cl3 (n = 35), differing for PROP responsiveness and FPD only. Results encourage future studies to explore association between GOT and both perception and preference for different food texture. Furthermore, deeper investigation of individual variability in sensitivity to different types of oral tactile stimuli would be helpful to capture differences in tactile sensitivity among the most sensitive individuals.