Sleep quality burden in chronic rhinosinusitis with nasal polyps and its modulation by dupilumab.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with a substantial burden on patients' quality of life and impaired sleep quality. The most common CRSwNP endotype is characterized by type 2 inflammation, with enhanced production of interleukin (IL)-4, IL-5, and IL-13. Dupilumab is a monoclonal antibody against IL-4 receptor-α, which inhibits both IL-4 and IL-13 signaling, and was recently approved for treatment of CRSwNP. OBJECTIVE: We investigated the effect of dupilumab on the sleep quality of patients with CRSwNP in a real-life setting. METHODS: Patients were evaluated at baseline and after 1 and 3 months of dupilumab treatment by means of the Epworth sleepiness scale (ESS), insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI), and sinonasal outcome test 22 (SNOT-22) sleep domain. RESULTS: A total of 29 consecutive patients were enrolled, and their baseline sleep quality assessment were as follows: ESS of 7.9 (± 4.5); ISI of 13.1 (± 6.2); PSQI of 9.2 (± 3.7); and SNOT-22 sleep domain of 12.1 (± 4.2). Excessive daily sleepiness, insomnia, and globally impaired sleep quality were present in 24.1%, 79.3%, and 93.1% respectively. Treatment with dupilumab was associated with significant improvement in ESS, ISI, PSQI, and SNOT-22 sleep domain with concomitant reduction of the proportion of patients with insomnia and globally impaired sleep quality. CONCLUSION: CRSwNP was associated with a significant impact on global sleep quality, in particular, insomnia, and treatment with dupilumab induced a rapid improvement (after 1 single month of treatment) in all the sleep quality parameters, suggesting that sleep disturbances should be more carefully evaluated as an additional outcome in these patients.

Mast Cells in Upper and Lower Airway Diseases: Sentinels in the Front Line.

Mast cells (MCs) are fascinating cells of the innate immune system involved not only in allergic reaction but also in tissue homeostasis, response to infection, wound healing, protection against kidney injury, the effects of pollution and, in some circumstances, cancer. Indeed, exploring their role in respiratory allergic diseases would give us, perhaps, novel therapy targets. Based on this, there is currently a great demand for therapeutic regimens to enfeeble the damaging impact of MCs in these pathological conditions. Several strategies can accomplish this at different levels in response to MC activation, including targeting individual mediators released by MCs, blockade of receptors for MC-released compounds, inhibition of MC activation, limiting mast cell growth, or inducing mast cell apoptosis. The current work focuses on and summarizes the mast cells' role in pathogenesis and as a personalized treatment target in allergic rhinitis and asthma; even these supposed treatments are still at the preclinical stage.

Operations and thermodynamics of an artificial rotary molecular motor in solution.

A general framework is provided that makes possible the estimation of time-dependent properties of a stochastic system moving far from equilibrium. The process is investigated and discussed in general terms of nonequilibrium thermodynamics. The approach is simple and can be exploited to gain insight into the dynamics of any molecular-level machine. As a case study, the dynamics of an artificial molecular rotary motor, similar to the inversion of a helix, which drives the motor from a metastable state to equilibrium, are examined. The energy path that the motor walks was obtained from the results of atomistic calculations. The motor undergoes unidirectional rotation and its entropy, internal energy, free energy, and net exerted force are given as a function of time, starting from the solution of Smoluchowski's equation. The rather low value of the organization index, that is, the ratio of the work done by the particle against friction during the unidirectional motion per available free energy, reveals that the motion is mainly subject to randomness, and the amount of energy converted to heat due to the directional motion is very small.

Mind the Metabolic Gap: Bridging Migraine and Alzheimer's disease through Brain Insulin Resistance.

Brain insulin resistance has recently been described as a metabolic abnormality of brain glucose homeostasis that has been proven to downregulate insulin receptors, both in astrocytes and neurons, triggering a reduction in glucose uptake and glycogen synthesis. This condition may generate a mismatch between brain's energy reserve and expenditure, mainly during high metabolic demand, which could be involved in the chronification of migraine and, in the long run, at least in certain subsets of patients, in the prodromic phase of Alzheimer's disease, along a putative metabolic physiopathological continuum. Indeed, the persistent disruption of glucose homeostasis and energy supply to neurons may eventually impair protein folding, an energy-requiring process, promoting pathological changes in Alzheimer's disease, such as amyloid-ß deposition and tau hyperphosphorylation. Hopefully, the "neuroenergetic hypothesis" presented herein will provide further insight on there being a conceivable metabolic bridge between chronic migraine and Alzheimer's disease, elucidating novel potential targets for the prophylactic treatment of both diseases.

Occupational noise exposure at sea: A socio-legal study on fish harvesters' perceptions in Newfoundland and Labrador, Canada.

Introduction: Noise is a significant health hazard for fish harvesters. Chronic exposure to hazardous noise levels of 85 dB (A) for an 8-h work shift can have adverse health impacts, including both auditory and non-auditory health problems such as noise-induced hearing loss, stress, hypertension, sleeping disorders, and impaired cognitive performance. Methods: A review of legislation and policies governing workplace noise exposure, as well as qualitative, semi-structured interviews, were conducted to assess how fish harvesters in Newfoundland and Labrador (NL) manage onboard occupational noise exposure and perceive noise-induced health problems, as well as the barriers and challenges associated with preventing and controlling noise exposure. Results: The legal review shows no compulsory noise preventive measure at the fishing vessel design stage in Canada. Limited implementation of Occupational Health and Safety (OHS) regulations to control and prevent onboard noise by employers in Newfoundland and Labrador. Fishers reported that their workplace is noisy. Over time, fish harvesters adapted to the environment and learned to tolerate loud noise, displaying fatalistic behavior. Fish harvesters reported avoiding using hearing protection onboard due to navigation safety concerns. Fishers reported hearing loss as well as other non-auditory health problems. Inadequate noise control measures adopted by employers, a limited supply of hearing protection onboard, and a lack of regular hearing testing, training, and education were identified as the main barriers to preventing and controlling noise exposure. Conclusion: Proper implementation of NL OHS regulations and the development of hearing conservation initiatives by employers are necessary. All stakeholders, including the federal and provincial governments, WorkplaceNL, and not-for-profit fishing organizations in the province, are strongly recommended to initiate training and education campaigns to help fish harvesters understand noise exposure and adopt preventive measures.

Real-world data: A relevant component in the framework of scientific evidence.

Explanatory randomized controlled clinical trials test hypotheses to see if the intervention causes an outcome of interest in optimal circumstances, that is, established by selecting patients based on inclusion and exclusion criteria and controlled environments. They assess the "efficacy" of an intervention. On the contrary, it is crucial for society to address issues related to real-world clinical practices. This need can be fulfilled by real-world studies. We discuss the challenges in obtaining real-world evidence in asthma, debating the importance of including patients who are typically excluded from randomized controlled clinical trials to ensure the generalizability of the results. We conclude by discussing the integration of real-world evidence in guidelines and the need for standard rules to use real-world evidence in guidelines.

The Prevalence of Immediate Hypersensitivity Reactions to the BNT162b2 mRNA Vaccine against SARS-CoV-2: Data from the Vaccination Campaign in a Large Academic Hospital.

The anti-SARS-CoV-2 vaccination has probably been the most effective tool for preventing the infection and negative outcomes of the COVID-19 disease, and therefore for interrupting the pandemic state. The first licensed SARS-CoV-2 vaccine was BNT162b2, an mRNA vaccine that has been widely used since the earliest stages of the global vaccination campaign. Since the beginning of the vaccination campaign, some cases of suspected allergic reactions to BNT162b2 have been described. Epidemiological data, however, have provided reassuring results of an extremely low prevalence of these hypersensitivity reactions to anti-SARS-CoV-2 vaccines. In this article, we describe the results of a survey carried out through the use of a questionnaire, administered to all the health personnel of our university hospital after the first two doses of the BNT162b2 vaccine, which investigated the development of adverse reactions after a vaccination. We analyzed the responses of 3112 subjects subjected to the first dose of the vaccine; among these, 1.8% developed symptoms compatible with allergic reactions and 0.9% with clinical manifestations of possible anaphylaxis. Only 10.3% of the subjects who had allergic reactions after the first injection experienced similar reactions after the second dose and none of them experienced anaphylaxis. In conclusion, the anti-SARS-CoV-2 vaccination is rarely associated with severe allergic reactions and the second dose of vaccine is safe for this group of patients.

Desensitization Protocols for Anti-SARS-CoV-2 Vaccines in Patients with High Risk of Allergic Reactions.

Vaccines for SAR-CoV-2 are the most effective preventive treatment able to reduce the risk of contracting the infection and experiencing worse outcomes whenever the infection is contracted. Despite their rarity, hypersensitivity reactions to the anti-SARS-CoV-2 vaccine have been described and could become the reason not to complete the vaccination. Desensitization protocols for other vaccines have been described and validated, while the use of this approach for anti-SARS-CoV-2 vaccines is still anecdotal. We herein describe our experience with 30 patients with previous allergic reactions to anti-SARS-CoV-2 vaccines or to any of their excipients, proving that they are effective and safe; only two patients experienced hypersensitivity reaction symptoms during the desensitization procedure. Moreover, in this article, we propose desensitization protocols for the most common anti-SARS-CoV-2 vaccines.

Polyethylene Glycol and Polysorbate 80 Skin Tests in the Context of an Allergic Risk Assessment for Hypersensitivity Reactions to Anti-SARS-CoV-2 mRNA Vaccines.

Concern has arisen about hypersensitivity reactions in patients with allergic reactions to drugs containing polyethylene glycol (PEG) or polysorbate 80 (PS80), excipients of currently available anti-SARS-CoV-2 mRNA vaccines. However, the actual utility of PEG and PS80 skin allergy testing is currently still debated. We retrospectively analyzed all cases of patients on whom we performed allergometric skin tests for PEG and PS80 in the context of a pre-vaccination screening (for patients with multiple hypersensitivity reactions to drugs for which these excipients were among the suspected agents) or following suspected hypersensitivity reactions to anti-SARS-CoV-2 vaccines. A total of 134 tests were performed for PEG and PS80, eight of which produced uninterpretable results (due to dermographism or non-specific reactions). Of the remaining 126 cases (85 pre-vaccinal and 41 post-vaccine reactions), 16 (12.7%) were positive for PEG and/or PS80. Stratifying by clinical indication, there were no statistically significant differences in the proportion of positive tests between patients evaluated in the context of the pre-vaccination screening and those evaluated after a vaccine reaction (10.6% vs. 17.1%, respectively, p = 0.306). Allergometric skin tests for PEG and PS80 in our case series resulted positive in an unexpectedly high proportion of patients, suggesting that testing for allergy to these two excipients should not be ignored in case of reasonable clinical suspicion.

Migraine, Brain Glucose Metabolism and the "Neuroenergetic" Hypothesis: A Scoping Review.

Increasing evidence suggests that migraine may be the result of an impaired brain glucose metabolism. Several studies have reported brain mitochondrial dysfunction, impaired brain glucose metabolism and gray matter volume reduction in specific brain areas of migraineurs. Furthermore, peripheral insulin resistance, a condition demonstrated in several studies, may extend to the brain, leading to brain insulin resistance. This condition has been proven to downregulate insulin receptors, both in astrocytes and neurons, triggering a reduction in glucose uptake and glycogen synthesis, mainly during high metabolic demand. This scoping review examines the clinical, epidemiologic and pathophysiologic data supporting the hypothesis that abnormalities in brain glucose metabolism may generate a mismatch between the brain's energy reserve and metabolic expenditure, triggering migraine attacks. Moreover, alteration in glucose homeostasis could generate a chronic brain energy deficit promoting migraine chronification. Lastly, insulin resistance may link migraine with its comorbidities, like obesity, depression, cognitive impairment and cerebrovascular diseases. PERSPECTIVE: Although additional experimental studies are needed to support this novel "neuroenergetic" hypothesis, brain insulin resistance in migraineurs may unravel the pathophysiological mechanisms of the disease, explaining the migraine chronification and connecting migraine with comorbidities. Therefore, this hypothesis could elucidate novel potential approaches for migraine treatment.

A Comparative Study of the Methods to Assess Occupational Noise Exposures of Fish Harvesters.

BACKGROUND: Noise-induced hearing loss is a well-known occupational disease that affects many fish harvesters from many fisheries worldwide, whose risk factor is prolonged exposure to hazardous noise levels. To date, academic research activities and regulatory bodies have not provided any comparative analysis among the existing methods to assess noise exposure levels of fish harvesters. This paper provides a comparison of four relevant assessment methods of noise exposure, examining the results of a measurement campaign performed onboard small fishing vessels from Newfoundland and Labrador. METHODS: We traveled onboard 11 vessels engaged in multiple fisheries from Newfoundland and Labrador and performed extensive noise exposure surveys using the simplified International Maritime Organization method, the full-day measurement method, and the two methods provided by ISO 9612:2009, the task-based method and job-based method (JBM). RESULTS: The results showed that the four methods yield similar values when the noise components are dominated by the engine and auxiliaries (steady-state sources); when noise components are dominated by the fishing gear, task-based method and the simplified International Maritime Organization method estimates are less accurate than JBM, using full-day measurements as baseline. CONCLUSION: The JBM better assesses noise exposure in small-scale fisheries, where noise exposure has significant variance and uncertainties on the exposure levels are higher.

Occupational noise exposure and health impacts among fish harvesters: a systematic review.

BACKGROUND: Occupational noise exposure has been identified as a significant risk factor for fish harvesters. Chronic noise exposure causes hearing and other health problems and undermines the quality of life and well-being. This review paper aims to highlight noise-related auditory and non-auditory health effects among fish harvesters. MATERIALS AND METHODS: A systematic literature search approach was adopted using the following databases: PubMed, Embase, SCOPUS, Web of Science, Google Scholar, and by exploring grey literature. The literature search was conducted in 2020 (between October 15 and November 30). Relevant articles were explored by reviewing title, keywords, and abstract based on the inclusion and exclusion criteria. The full-text critical review of selected papers was made and finalized the most relevant studies. RESULTS: Initial 1,281 records were identified, exploring various databases and additional sources using relevant keywords. Duplicate articles were removed and retrieved 746 articles. After that, a screening of 746 research papers was done based on the selection criteria and finalised 28 articles for full-text review. Finally, articles were filtered based on the study's aim and extracted 17 papers for the final review. CONCLUSIONS: Noise-induced hearing loss was considered a significant health risk to fish harvesters across the studies, affecting physical and emotional well-being. The prevalence of hearing loss was observed from 6% to 80%. Other health problems, such as headache, dizziness, annoyance, stress, fatigue, elevated blood pressure, sleep disturbances, and impaired cognitive performance, were also reported. Further research is needed to validate the non-auditory health effects among fish harvesters.