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Background and Purpose: Aiming to achieve light sedation via intranasal administration, this study showed that propofol (PPF) did not permeate across the rabbit nasal mucosa ex vivo from its marketed emulsion for injection., Experimental Approach: Dilution of the emulsion with methyl-β-cyclodextrin in saline solution increased propofol solubility in water and diffusion across the nasal epithelium., Key Results and Conclusion: Despite these positive effects of the cyclodextrin, the amount of PPF permeated was minimal in 3 h, exceeding the formulation residence time in the nose. These results highlight the key role of formulation and the need for innovation in solubility and transmucosal transport enhancement techniques to optimize drug delivery and therapeutic efficacy., Competing Interests: Conflict of interest : The authors declare that they have no known competing financial interests nor personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 by the authors.)

Ethanol is the psychoactive substance identified most frequently in post-mortem specimens. Unfortunately, interpreting post-mortem ethanol concentrations can be difficult because of post-mortem alcohol redistribution and the possibility of post-mortem alcohol neogenesis. Indeed, in the time interval between death and sample collection, the decedent may be exposed to non-controlled environments for an extended period, promoting microbial colonization. Many authors report that in the presence of carbohydrates and other biomolecules, various species of bacteria, yeast, and fungi can synthesize ethanol and other volatile substances in vitro and in vivo. The aim of this study was to study the impact of several variables on microbial ethanol production as well as develop a mathematical model that could estimate the microbial-produced ethanol in correlation with the most significant consensual produced higher alcohol, 1-propanol. An experimental setup was developed using human blood samples and cadaveric fragments incubated under strictly anaerobic conditions to produce a novel substrate, "cadaveric putrefactive blood" mimicking post-mortem corpse conditions. The samples were analyzed daily for ethanol and 1-propanol using an HS-GC-FID validated method. The formation of ethanol was evaluated considering different parameters such as putrefactive stage, blood glucose concentration, storage temperature, and storage time. Statistical analysis was performed using the Mann-Whitney non-parametric test and simple linear regression. The results indicate that the early putrefactive stage, high blood glucose concentration, high temperature, and time of incubation increase microbial ethanol production. In addition, the developed mathematical equation confirms the feasibility of using 1-propanol as a marker of post-mortem ethanol production., (© 2024 American Academy of Forensic Sciences.)

Computed tomography (CT)-guided percutaneous needle biopsy of the lung is a well-recognized and relatively safe diagnostic procedure for suspicious lung masses. Systemic air embolism (SAE) is a rare complication of transthoracic percutaneous lung biopsies. Herein, we present a case of an 81-year-old man who underwent CT-guided percutaneous needle biopsy of a suspicious nodule in the lower lobe of the right lung. Shortly after the procedure, the patient coughed up blood which prompted repeat CT imaging. He was found to have a massive cardiac air embolism. The patient became unresponsive and, despite resuscitation efforts, was pronounced dead. The pathophysiology, risk factors, clinical features, radiological evidence, and autopsy findings associated with SAE are discussed, which may, in light of the current literature, assist with the dilemma between assessing procedural complications and medical liability. Given the instances of SAE in the setting of long operative procedures despite careful technical execution, providing accurate and in-depth information, including procedure-related risks, even the rarest but potentially fatal ones, is recommended for informed consent to reduce medicolegal litigation issues., (© 2023. The Author(s).)

Background: New drugs to tackle the next pathway or mutation fueling cancer are constantly proposed, but 97% of them are doomed to fail in clinical trials, largely because they are identified by cellular or in silico screens that cannot predict their in vivo effect., Methods: We screened an Adeno-Associated Vector secretome library (> 1000 clones) directly in vivo in a mouse model of cancer and validated the therapeutic effect of the first hit, EMID2, in both orthotopic and genetic models of lung and pancreatic cancer., Results: EMID2 overexpression inhibited both tumor growth and metastatic dissemination, consistent with prolonged survival of patients with high levels of EMID2 expression in the most aggressive human cancers. Mechanistically, EMID2 inhibited TGFβ maturation and activation of cancer-associated fibroblasts, resulting in more elastic ECM and reduced levels of YAP in the nuclei of cancer cells., Conclusion: This is the first in vivo screening, precisely designed to identify proteins able to interfere with cancer cell invasiveness. EMID2 was selected as the most potent protein, in line with the emerging relevance of the tumor extracellular matrix in controlling cancer cell invasiveness and dissemination, which kills most of cancer patients., (© 2024. The Author(s).)

Obstructive sleep apnea (OSA) is a multifactorial sleep breathing disorder, seriously impacting quality of life and involving approximately 1 billion of the world's population. It is characterized by episodes of total cessation of breathing or decreases in airflow during sleep. Available data suggest that most cases of OSA remain undiagnosed even in developed countries. This is due to a lack of widespread knowledge about this pathology and the medical morbidities and mortality it brings about, among both laypeople and physicians. Moreover, despite receiving indications about the need to undergo specific evaluations for OSA signs and symptoms, sometimes patients do not pay sufficient attention to the problem. This is probably due to a lack of correct information on these issues. The present investigation analyzed the level of knowledge about OSA pathology and the sources through which a group of OSA patients gained information on their condition. A survey of 92 patients diagnosed with OSA (mean age 60.55 ± 10.10) and referred to the Unit of Orthodontics and Dental Sleep Medicine of the University of Bologna was conducted by means of a questionnaire investigating sociodemographic characteristics, the level of general knowledge on OSA pathology and its possible medical consequences. Despite about two third (67.38%) of the population demonstrating extensive knowledge, remarkably, a group of subjects (20.65%) had poor awareness of the OSA condition. A statistically significant correlation emerged between the level of knowledge about OSA and the level of education ( p = 0.002). A great effort should be made to improve the quality of information and the communication modalities for OSA to enable a fully appropriate awareness of the condition among patients.

The need for providing rapid and, possibly, on-the-spot analytical results in the case of intoxication has prompted researchers to develop rapid, sensitive, and cost-effective methods and analytical devices suitable for use in nonspecialized laboratories and at the point of need (PON). In recent years, the technology of paper-based microfluidic analytical devices (μPADs) has undergone rapid development and now provides a feasible, low-cost alternative to traditional rapid tests for detecting harmful compounds. In fact, µPADs have been developed to detect toxic molecules (arsenic, cyanide, ethanol, and nitrite), drugs, and drugs of abuse (benzodiazepines, cathinones, cocaine, fentanyl, ketamine, MDMA, morphine, synthetic cannabinoids, tetrahydrocannabinol, and xylazine), and also psychoactive substances used for drug-facilitated crimes (flunitrazepam, gamma-hydroxybutyric acid (GHB), ketamine, metamizole, midazolam, and scopolamine). The present report critically evaluates the recent developments in paper-based devices, particularly in detection methods, and how these new analytical tools have been tested in forensic and clinical toxicology, also including future perspectives on their application, such as multisensing paper-based devices, microfluidic paper-based separation, and wearable paper-based sensors.

Obstructive sleep apnea (OSA) is a highly prevalent sleep breathing disorder characterized by the collapse of the pharyngeal walls that entails recurrent episodes of cessation of breathing or decrease in airflow while sleeping. This results in sleep fragmentation, decreased oxygen saturation and an increase in the partial pressure of carbon dioxide, causing excessive daytime sleepiness, hypertension and increased prevalence of cardiovascular morbidity and mortality. Mandibular advancement devices (MAD) represent a valid alternative therapy to Continuous Positive Airway Pressure, thrusting the mandible forward, increasing the lateral diameter of the pharynx and reducing the collapsibility of the airway. Several investigations have focused on the detection of the best mandibular advancement amount in terms of effectiveness and tolerance, but few and contrasting data are available on the role of occlusal bite raise in reducing the apnea/hypopnea index (AHI). The aim of this systematic review with meta-regression analysis was to investigate the effect of the bite raise of MAD on AHI values in adult patients affected by OSA. An electronic search was performed in MEDLINE, the Cochrane Database, Scopus, Web of Science and LILACS. Randomized controlled trials (RCT) investigating the effectiveness of MAD in OSA patients were included. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and the risk of bias with the Cochrane risk-of-bias tool for randomized trials (RoB2). Six RCT were included. The success rate of each study was computed: (mean baseline AHI - mean post treatment AHI)/mean baseline AHI. The GRADE scores indicated that the quality of evidence was very low. The meta-regression analysis showed that there was no correlation between the occlusal bite raise and the AHI improvement.

Background: The gold standard for the diagnosis of sleep bruxism (SB) is laboratory polysomnography (L-PSG) recording. However, many clinicians still define SB using patients' self-assessment and/or clinical tooth wear (TW). The purpose of this cross-sectional controlled study was to compare the prevalence of TW, head-neck muscles sensitivity and Temporomandibular Disorders (TMD) between SB and non-SB patients diagnosed with L-PSG in a cohort of patient with sleep disorders (SD)., Methods: 102 adult subjects with suspected SD underwent L-PSG recording to assess the presence of sleep disorder and SB. TW was clinically analyzed using TWES 2.0. The pressure pain threshold (PPT) of masticatory muscles were assessed using a Fisher algometer. Diagnostic criteria for TMD (DC/TMD) were used to evaluate the presence of TMD. SB self-assessment questionnaires were administered. TWES score, PPT, TMD prevalence and questionnaire results were compared between SB and non-SB patients., Results: 22 SB patients and 66 non-SB patients with SD were included. No significant differences emerged between groups in regards to TW, the PPT values, or SB's self-assessment questionnaires as well the prevalence of TMD., Conclusion: in a SD population, TW is not pathognomonic of active SB and SB self-assessment is not reliable. There seems to be no correlation between SB, TMD and head/neck muscle sensitivity.

Background: Obstructive sleep apnoea (OSA) is characterised by partial or complete obstruction of the upper airways during sleep and it has been associated with temporomandibular disorders (TMDs) on the basis of several pathophysiological hypotheses., Objectives: To assess the prevalence of TMDs in a population of patients affected by OSA compared to a control group of subjects not affected by OSA., Methods: A cross-sectional controlled study was conducted on a group subjects studied by polygraphy (PG) at the snoring section of the ENT department, Sant'Orsola-Malpighi Hospital - University of Bologna. Patients who received a diagnosis of OSA were included in the study group and subjects with a negative PG diagnosis for Sleep Disordered Breathing and PG respiratory pattern that did not suggest the occurrence of sleep disorders were enrolled in the control group. Both the subjects included in the study group and the control group underwent an examination following the Diagnostic Criteria for Temporomandibular Disorders Axis I and II., Results: Forty-three OSA patients (29 M, 16 F, mean age 52.26 ± 11.40) and 43 healthy controls (25 M, 18 F, mean age 49.95 ± 7.59) were included in the study. No significant differences were found between groups in demographic data. TMD prevalence and Axis II results did not differ between groups., Conclusions: This paper does not highlight a higher prevalence of TMDs in adults with OSA compared to healthy controls. Further high-quality studies are needed to confirm the results and to give possible pathophysiological explanations, providing reliable evidence., (© 2023 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Background: Despite increasing scientific interest in the effectiveness of mandibular advancement device (MAD) for the treatment of obstructive sleep apnoea (OSA), laypeople lack knowledge about this treatment option., Objectives: To investigate content, quality and readability of the online information regarding MAD., Methods: Google, Yahoo and Bing were searched for 'sleep apnea', 'mandibular advancement device' and 'oral appliance'. Websites were analysed for content (multidisciplinary care team, qualified dentist, treatment contraindications and side effects), as well as for quality (DISCERN instrument, HONcode) and readability scores (Flesch Reading Ease, FRE and Flesch-Kincaid Reading Grade, FKG)., Results: Totally, 155 websites were included: 53% from health professionals, 20% commercial, 17% academic and 10% from non-health professionals. Content was incomplete, especially for commercial ones. 71.61% websites failed to acknowledge treatment contraindications, approximately 40.00% did not mention side effects and the need for a multidisciplinary care team, while 22.58% did not address the need to consult a qualified dentist. Quality and reliability were poor. Mean DISCERN score was 39.93 (95% CI 37.90-41.96), with lower scores for commercial websites compared with others. Only nine websites displayed HONcode certification. Readability was quite difficult, with mean FRE score of 59.50 (95% CI 57.58-61.42) and mean FKG level of 6.92 (95% CI 6.64-7.21)., Conclusion: Health care professionals should be aware that currently available online information do not fulfil the most important aspects of MAD therapy and may be difficult to understand by laypeople. This could contribute to cause delays in appropriate OSA care and unrealistic treatment expectations, increasing the risk of treatment discontinuation., (© 2022 John Wiley & Sons Ltd.)

Statins are cholesterol-lowering medications which are widely prescribed as first-line treatment for hyperlipidemia, against high blood cholesterol aimed at reducing the risk of atherosclerotic diseases. Notwithstanding their undoubted efficacy, the needed long-term treatment with these drugs is characterized by a high percentage of dropout. Consequently, an effective tool to verify the patients' compliance to statin therapy is needed. In this context, the analysis for drugs and drug metabolites in the hair may represent an almost ideal tool because, according to a sound body of forensic toxicological literature, concentrations in the hair matrix reflect the chronic intake of drugs and pharmaceuticals. In this light, in the present study, a novel, specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method has been developed to determine six statins and their metabolites (namely atorvastatin, (p)α-OH-atorvastatin-lactone, (o)α-OH-atorvastatin-lactone, rosuvastatin, N-desmethyl rosuvastatin and pravastatin) in human hair. After optimization, the method was successfully validated in terms of selectivity, linearity, sensitivity, precision, accuracy, stability and matrix effect. Moreover, the practical applicability of this method for verifying adherence to statin therapy was assessed by testing samples of hair collected from subjects under long-term therapy with statins., (© 2023 The Authors. Electrophoresis published by Wiley-VCH GmbH.)

Headspace gas chromatography with a flame ionization detector (HS-GC-FID) is a well-established approach for determining blood alcohol concentration, including in cadaveric specimens. Although the integrity of blood specimens can be adequately guaranteed after the sampling, the quantification of ethanol in cadaveric blood can be affected by postmortem fermentative phenomena occurring between the time since death and the sampling of biofluids. The vitreous humor is less affected by putrefactive phenomena allowing compound determination and its use as an alternative biological matrix. The present work aimed to develop and validate a method using the salting-out effect and based on HS-GC-FID for the determination of ethanol in the vitreous humor. The reported analytical method is based on a simple vitreous humor pre-treatment consisting of a dilution (1:9) with a solution of 2.5 mol/L K2CO3 and 0.0012 mol/L tert-butanol (internal standard). After 1 min of incubation, part of the specimen evaporated in the headspace (2,000 µL) is injected into the chromatographic system and analyzed in isothermal mode (40°C), with a chromatographic time of 1.6 min. The method was validated in terms of selectivity, the lowest limit of detection, intraday and total imprecision, and trueness (bias). The determination of ethanol in the vitreous humor and blood was carried out in 75 cases. The correlation between the two matrices was confirmed in 61 cases. However, 14 vitreous humor specimens showed lower ethanol concentrations, and in the related blood specimens, it was possible to identify the signal of n-propanol, a typical product of postmortem microbial fermentation, that justifies the excess of ethanol in the blood specimens., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The relevance of the problem of urine tampering is well-known in forensic toxicology, with sample dilution being the most used method to cheat toxicological controls. Among the criteria to assess urine integrity, the quantification of creatinine probably represents the most popular method. The present paper presents a simple and low-cost analytical device for on-site creatinine determination as first-line screening for urine dilution. The proposed microfluidic devices were designed as a three-dimensional origami pattern. The device included three colorimetric reactions based on picric acid (PA-based reagent), 3,5-dinitrobenzoic acid (DNBA-based reagent), and Nessler's reagent. The last one, to the best of our knowledge, has never been used before for creatinine determination. In order to assure the highest ease and economy of operation, the color detection and data processing were performed using a built-in smartphone camera and the associated software. The optimized device showed a detection limit of 0.02 g/L. The proposed method was used for the qualitative screening for urine dilution of 48 samples, showing a diagnostic sensitivity and specificity for PA-based, DNBA-based and Nessler's reagent of 83.3%-80.0%, 72.2%-70.0%, and 100.0%-93.3% respectively, versus reference enzymatic method adopting a cut-off of 0.2 g/L. In conclusion, the present preliminary study shows that the proposed device could be a useful tool for on-site screening for urine tampering at the time of sample collection for toxicological testing., Competing Interests: Declaration of competing interest 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Diverse genetic backgrounds often lead to phenotypic heterogeneity in cardiomyopathies (CMPs). Previous genotype-phenotype studies have primarily focused on the analysis of a single phenotype, and the diagnostic and prognostic features of the CMP genotype across different phenotypic expressions remain poorly understood., Objectives: We sought to define differences in outcome prediction when stratifying patients based on phenotype at presentation compared with genotype in a large cohort of patients with CMPs and positive genetic testing., Methods: Dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, and biventricular arrhythmogenic cardiomyopathy were examined in this study. A total of 281 patients (80% DCM) with pathogenic or likely pathogenic variants were included. The primary and secondary outcomes were: 1) all-cause mortality (D)/heart transplant (HT); 2) sudden cardiac death/major ventricular arrhythmias (SCD/MVA); and 3) heart failure-related death (DHF)/HT/left ventricular assist device implantation (LVAD)., Results: Survival analysis revealed that SCD/MVA events occurred more frequently in patients without a DCM phenotype and in carriers of DSP, PKP2, LMNA, and FLNC variants. However, after adjustment for age and sex, genotype-based classification, but not phenotype-based classification, was predictive of SCD/MVA. LMNA showed the worst trends in terms of D/HT and DHF/HT/LVAD., Conclusions: Genotypes were associated with significant phenotypic heterogeneity in genetic cardiomyopathies. Nevertheless, in our study, genotypic-based classification showed higher precision in predicting the outcome of patients with CMP than phenotype-based classification. These findings add to our current understanding of inherited CMPs and contribute to the risk stratification of patients with positive genetic testing., Competing Interests: Funding Support and Author Disclosures This study was supported by National Institutes of Health (NIH) grants R01HL69071, R01HL116906, and R01HL147064, and American Heart Association grant 17GRNT33670495 (to Dr Mestroni); NIH grant 1K23HI067915; NIH grants 2UM1HG006542 and R01HL109209 (to Dr Taylor); and CRTrieste Foundation and Cassa di Risparmio di Gorizia Foundation (to Dr Sinagra). This work is also supported by NIH/National Center for Advancing Translational Sciences Colorado CTSA grant numbers UL1 TR002535 and UL1 TR001082. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It is well known that traffic injuries still represent one of the main causes of death and that high blood alcohol concentrations while driving significantly increase the occurrence of accidents. However, only limited literature on the correlation between chronic alcohol abuse and accident risk is available. The aim of the present study was to investigate the hypothesis of an association between elevated concentrations of carbohydrate deficient transferrin (CDT) and the occurrence of alcohol-related traffic accidents., Methods: The analytical determinations of BAC and CDT were performed following certified methods in HS-GC-FID and HPLC, respectively. For BAC, 0.50 g/L was used as cut-off, whereas 2.0% was used for CDT, according to the standardisation proposed by IFCC. A total of 929 drivers, tested for BAC at the time of hospital admission after a traffic accident, were classified into two groups: InjDr 1 (BAC ≤ 0.50 g/L) and InjDr 2 (BAC>0.50 g/L); all drivers were also tested for CDT., Results: InjDr 1 included 674 individuals, only 2.5% showing a CDT above the cutoff, whereas InjDr 2 group consisted of 255 subjects, 28.6% testing positive for CDT (Odds Ratio 15.5). When subdividing the InjDr group into increasing classes of CDT, a steady increase in the percentage of BAC-positive drivers was appreciated. Moreover, average BAC was found to parallel each class of CDT., Conclusions: The reported data strongly support the use of CDT as a biomarker of increased risk of alcohol-related traffic accidents in the procedures of re-granting of the driving license upon confiscation for "drink driving"., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The optimization of oral health before allogeneic hematopoietic cell transplantation (HCT) is important for preventing infectious complications during treatment., Objective: The objective of this study was to evaluate the oral health condition and dental treatments performed in patients in pre-allogeneic HCT., Method: The records of patients treated during 2018 at a Brazilian HCT service were reviewed. The following oral health data were obtained: 1. Decayed, missing and filled teeth / correlated index for primary dentition (DMFT/dmft); 2. Quality of oral hygiene and 3. Dental pathologies: 3.1 Periodontal infectious focus, 3.2 Endodontic infectious focus and 3.3 Carie incidence. All dental procedures performed were surveyed., Results: Thirty-three patients were included, with a mean age of 28.42 (±16.37), 20 male (60%) and 13 female. The average DMFT/dmft found in this study was 10.24 (± 8.37), similar to the index found in the population in southeastern Brazil. The younger study population presented a DMFT/dmft considered high, when compared to the general population. A total of 27.2% of the patients had active caries lesions, 33.3%, foci of periodontal infection, 15.1%, endodontic infectious focus and 40%, poor oral hygiene. Almost half of the patients (48.4%) had to undergo dental intervention, 24.2% needing periodontal scaling, 21.2%, fillings and 12.1%, tooth extractions., Conclusion: We conclude that the studied population had an important incidence of dental pathologies and infectious conditions that could complicate throughout HCT, especially in younger patients, therefore presenting a high demand for dental treatment in the pre-HCT. Studies that assess the impact of dental conditioning on the outcomes of HCT with an emphasis on dental infectious complications, days of hospitalization and survival are necessary.", (Copyright © 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Therapies for patients with myocardial infarction and heart failure are urgently needed, in light of the breadth of these conditions and lack of curative treatments. To systematically identify previously unidentified cardioactive biologicals in an unbiased manner in vivo, we developed cardiac FunSel, a method for the systematic, functional selection of effective factors using a library of 1198 barcoded adeno-associated virus (AAV) vectors encoding for the mouse secretome. By pooled vector injection into the heart, this library was screened to functionally select for factors that confer cardioprotection against myocardial infarction. After two rounds of iterative selection in mice, cardiac FunSel identified three proteins [chordin-like 1 (Chrdl1), family with sequence similarity 3 member C (Fam3c), and Fam3b] that preserve cardiomyocyte viability, sustain cardiac function, and prevent pathological remodeling. In particular, Chrdl1 exerted its protective activity by binding and inhibiting extracellular bone morphogenetic protein 4 (BMP4), which resulted in protection against cardiomyocyte death and induction of autophagy in cardiomyocytes after myocardial infarction. Chrdl1 also inhibited fibrosis and maladaptive cardiac remodeling by binding transforming growth factor-β (TGF-β) and preventing cardiac fibroblast differentiation into myofibroblasts. Production of secreted and circulating Chrdl1, Fam3c, and Fam3b from the liver also protected the heart from myocardial infarction, thus supporting the use of the three proteins as recombinant factors. Together, these findings disclose a powerful method for the in vivo, unbiased selection of tissue-protective factors and describe potential cardiac therapeutics.

Introduction and Methods: Skeletal muscle mitochondrial dysfunction may cause tissue oxidative stress and consequent catabolism in chronic kidney disease (CKD), contributing to patient mortality. We investigated in 5/6-nephrectomized (Nx) rats the impact of n3-polyunsaturated fatty-acids (n3-PUFA) isocaloric partial dietary replacement on gastrocnemius muscle (Gm) mitochondrial master-regulators, ATP production, ROS generation and related muscle-catabolic derangements., Results: Nx had low Gm mitochondrial nuclear respiratory factor-2 and peroxisome proliferator-activated receptor gamma coactivator-1alpha, low ATP production and higher mitochondrial fission-fusion protein ratio with ROS overproduction. n3-PUFA normalized all mitochondrial derangements and pro-oxidative tissue redox state (oxydized to total glutathione ratio). n3-PUFA also normalized Nx-induced muscle-catabolic proinflammatory cytokines, insulin resistance and low muscle weight. Human uremic serum reproduced mitochondrial derangements in C2C12 myotubes, while n3-PUFA coincubation prevented all effects. n3-PUFA also enhanced muscle mitophagy in-vivo and siRNA-mediated autophagy inhibition selectively blocked n3-PUFA-induced normalization of C2C12 mitochondrial ROS production., Conclusions: In conclusion, dietary n3-PUFA normalize mitochondrial master-regulators, ATP production and dynamics in experimental CKD. These effects occur directly in muscle cells and they normalize ROS production through enhanced mitophagy. Dietary n3-PUFA mitochondrial effects result in normalized catabolic derangements and protection from muscle wasting, with potential positive impact on patient survival., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Viral myocarditis (VM) is an important cause of heart failure (HF) in children and adults. However, the molecular determinants involved in cardiac inflammation and cardiomyocyte necrosis remain poorly characterized, and cardioprotective molecules are currently missing. Here, we applied an in vivo method based on the functional selection (FunSel) of cardioprotective factors using AAV vectors for the unbiased identification of novel immunomodulatory molecules in a Coxsackievirus B3 (CVB3)-induced myocarditis mouse model. Two consecutive rounds of in vivo FunSel using an expression library of 60 cytokines were sufficient to identify five cardioprotective factors (IL9, IL3, IL4, IL13, IL15). The screening also revealed three cytokines (IL18, IL17b, and CCL11) that were counter-selected and likely to exert a detrimental effect. The pooled overexpression of the five most enriched cytokines using AAV9 vectors decreased inflammation and reduced cardiac dilatation, persisting at 1 month after treatment. Individual overexpression of IL9, the top ranking in our functional selection, markedly reduced cardiac inflammation and injury, concomitant with an increase of anti-inflammatory Th2-cells and a reduction of pro-inflammatory Th17- and Th22-cells at 14 days post-infection. AAV9-mediated FunSel cardiac screening identified IL9 and other four cytokines (IL3, IL4, IL13, and IL15) as cardioprotective factors in CVB3-induced VM in mice., (© 2022. The Author(s).)

Background: Mandibular advancement devices (MADs) are used as an alternative to continuous positive airways pressure to treat obstructive sleep apnoea (OSA) patients, but to date, specific data on the adherence to MAD therapy are lacking., Objectives: The aim of the present systematic review was to investigate the dropout rate and adherence of OSA patients to different custom-made (CM) and non-custom-made (NCM) MAD therapies., Search Methods: An electronic search was performed in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, LILACS and Web of Science., Selection Criteria: Randomised controlled trials (RCTs) assessing the compliance to customised and not customised MADs in the treatment of adult OSA patients were included., Data Collection and Analysis: The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and the risk of bias by the Cochrane Collaboration's tool for assessing risk of bias in RCT. The dropout rate of each study was computed and the adherence to MAD therapy in terms of hours per night and nights per week was extracted from each study., Results: Thirty-two RCTs were included. The risk of bias resulted low in most of the studies. The GRADE scores indicated that the quality of evidence was from very low to moderate. The meta-analyses showed that the mean dropout rate did not significantly differ between CM and NCM MADs: The overall mean dropout rate was 0.171 [0.128-0.213] with a mean follow-up of 4.1 months. The hours per night adherence was significantly higher for CM MADs (6.418 [6.033-6.803]) compared to NCM MADs (5.107 [4.324-5.890]. The meta-regression showed that the dropout rate increases significantly during time (p < .05)., Conclusions: There is a very low to moderate quality of evidence that the dropout rate of MAD therapy is similar among CM and NCM MADs, that the dropout rate increases significantly during time and that CM MADs have higher hours per night adherence compared with NCM MAD., Registration: The study protocol was registered on PROSPERO (n. CRD42020199866)., (© 2021 John Wiley & Sons Ltd.)

Background: In the context of fitness certification to hold the driving license, GGT and CDT have been used, sometimes in combination (γ-CDT), to exclude chronic alcohol abuse. The present study was carried out with the aim of comparing the power of these biomarkers as tools for the objective screening of subjects at high risk of alcohol-associated traffic injuries., Methods: 288 male drivers admitted to hospital after traffic accidents were examined by determination of GGT, CDT and BAC. The degree of association of GGT, CDT and γ-CDT with BAC was analysed using non-parametric statistics., Results: Partitioning the cases using the cut-off concentrations of 0.5 g/L for BAC (the legal limit adopted in most European countries), 55 U/L for GGT and 1.9% for CDT, a highly significant difference was found between the frequency of elevated GGT or CDT in cases where BAC was within the legal limits and those with elevated BAC values (Fisher's exact test: p < 0.001). However, the calculation of the odds ratio showed a much higher increase for CDT (28 times) than for GGT (6 times) in those drivers with a BAC above the Italian legal limit in comparison with those showing a BAC within the cut-off; conversely, γ-CDT does not provide any significant advantage vs. CDT alone., Conclusions: Both GGT and CDT provide objective evidence of an association with the occurrence of alcohol-related severe traffic accidents, but CDT shows superior association with these events. Therefore, CDT, notwithstanding higher costs, should be preferred in a forensic/certification context., (Copyright © 2021 Elsevier B.V. All rights reserved.)