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Correlation analysis revealed that mitochondrial proteins and the synaptic protein were strongly associated with cognitive performance. Conclusion ApoE isoforms influence mitochondrial structure and function, which likely leads to alteration in oxidative stress, synapses, and cognitive function. These mitochondria-related proteins may be a harbinger of cognitive decline in ApoE-ɛ4 carriers and provide novel therapeutic targets for prevention and treatment of AD.Objective To investigate intrarater reliability and concurrent and construct validity of muscle strength, balance, and functional mobility measures in individuals with noncongenital myotonic dystrophy type 1 (DM1). find more Methods Seventy-eight adults with noncongenital DM1 participated in visit 1, and 73 of the them participated in visit 2 separated by 1 to 2 weeks. The assessments consisted of muscle strength tests with handheld dynamometry (HHD) and stationary dynamometry in the lower limb. The balance tests consisted of the step test, Timed Up and Go test, feet-together stance, tandem stance, 1-leg stance, and modified Clinical Test of Sensory Integration and Balance on a balance platform. The functional mobility tests consisted of the 10-m walk test (10mWT) and 10-times Sit-to-Stand test. Results The HHD and stationary dynamometry had sufficient intrarater reliability for most muscle groups on a group (SEM% ≤15%) and individual (minimal detectable difference [MDD95%] ≤30%) level, but the HHD was most reliable. Stationary dynamometry measured a higher torque than HHD for all extensor muscles, but for single individuals, none of the devices were favored. Overall, intrarater reliability and validity were sufficient only for the dynamic balance tests, not the static balance tests. Both functional mobility tests were sufficiently reliable and valid, but the 10mWT was most reliable. Conclusion Overall, HHD is recommended as a reliable and valid tool for single individuals and for flexor muscles on a group level. For balance assessments, the dynamic balance tests are recommended as the most valid and reliable balance tests. Both functional mobility tests are recommended for valid and reliable outcomes, but the 10mWT was superior for reliability.Objectives To identify the chemicals released in I Quit Ordinary Smoking (IQOS) heat-not-burn tobacco aerosol and to assess their potential human health toxicity. Methods The heating temperature window of the IQOS heat-not-burn device was determined using a thermographic camera over a period of 100 s. Qualitative studies were performed using a novel real-time gas chromatograph-mass spectrometer set-up. link2 Aerosols from six tobacco-flavoured IQOS HeatSticks (Amber, Blue, Bronze, Sienna, Turquoise and Yellow) were collected in a 1 mL loop via a manual syringe attached to the sample-out port of the valve. The gas transport line was heated to 200°C in order to prevent the condensation of volatile species. Compound identification was performed using the NIST11 mass spectrometry database library (US National Institute of Standards and Technology), where only chemicals with a match of 70% and above were listed as identifiable. Results The temperature profile of the IQOS device revealed a non-combustive process employed in generating the tobacco aerosol. Real-time qualitative analysis revealed 62 compounds encompassing a broad spectrum of chemicals such as carbonyls, furans and phthalates, which are highly toxic. Discussion Our findings complement the qualitative studies previously performed by Philip Morris International and others via indirect sampling methods. By analysing the aerosols in real time, we have identified a total of 62 compounds, from which only 10 were in common with previous studies. Several identified species such as diacetyl, 2,3-pentanedione, hydroxymethylfurfural and diethylhexyl phthalate are classified as highly toxic, with the latter considered carcinogenic.Purpose The purpose of this study is to identify the extent of diagnostic error lawsuits related to point-of-care ultrasound (POCUS) in internal medicine, paediatrics, family medicine and critical care, of which little is known. Methods We conducted a retrospective review of the Westlaw legal database for indexed state and federal lawsuits involving the diagnostic use of POCUS in internal medicine, paediatrics, family medicine and critical care. Retrieved cases were reviewed independently by three physicians to identify cases relevant to our study objective. A lawyer secondarily reviewed any cases with discrepancies between the three reviewers. Results Our search criteria returned 131 total cases. Ultrasound was mentioned in relation to the lawsuit claim in 70 of the cases returned. In these cases, the majority were formal ultrasounds performed and reviewed by the radiology department, echocardiography studies performed by cardiologists or obstetrical ultrasounds. There were no cases of internal medicine, paediatrics, family medicine or critical care physicians being subjected to adverse legal action for their diagnostic use of POCUS. Conclusion Our results suggest that concerns regarding the potential for lawsuits related to POCUS in the fields of internal medicine, paediatrics, family medicine and critical care are not substantiated by indexed state and federal filed lawsuits.Background Use of routinely collected patient data for research and service planning is an explicit policy of the UK National Health Service and UK government. Much clinical information is recorded in free-text letters, reports and notes. These text data are generally lost to research, due to the increased privacy risk compared with structured data. We conducted a citizens' jury which asked members of the public whether their medical free-text data should be shared for research for public benefit, to inform an ethical policy. Methods Eighteen citizens took part over 3 days. Jurors heard a range of expert presentations as well as arguments for and against sharing free text, and then questioned presenters and deliberated together. They answered a questionnaire on whether and how free text should be shared for research, gave reasons for and against sharing and suggestions for alleviating their concerns. Results Jurors were in favour of sharing medical data and agreed this would benefit health research, but were more cautious about sharing free-text than structured data. They preferred processing of free text where a computer extracted information at scale. Their concerns were lack of transparency in uses of data, and privacy risks. They suggested keeping patients informed about uses of their data, and giving clear pathways to opt out of data sharing. Conclusions Informed citizens suggested a transparent culture of research for the public benefit, and continuous improvement of technology to protect patient privacy, to mitigate their concerns regarding privacy risks of using patient text data.The paediatric respiratory research community uses cohort studies extensively. However, the landscape of these studies and their quality of reporting has not been assessed.We performed a systematic review of publications on cohort studies reporting on paediatric lower respiratory problems published in 2018. We searched Medline and EMBASE and extracted data on the studies' and journals' characteristics. We assessed the number of items of the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist that a random sample (100 papers) reported. We analysed factors associated with the STROBE score and with the most poorly reported items, using Poisson and logistic regressionOf the 21 319 records identified, 369 full-text articles met our inclusion criteria. Most papers studied asthma aetiology through birth cohorts and were based in Europe or North America. The reporting quality was insufficient 15% reported the 22 STROBE items; median score 18 (IQR 16-21). The most poorly reported items were sources of bias, sample size, statistical methods, descriptive results and generalisability. None of the studies' or journals' factors were associated with the STROBE score.We need a joined effort of editors, reviewers and authors to improve the reporting quality of paediatric cohort studies on respiratory problems.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) pandemic has attracted interest because of its global rapid spread, clinical severity, high mortality rate, and capacity to overwhelm healthcare systems [1, 2]. SARS-CoV-2 transmission occurs mainly through droplets, although surface contamination contributes and debate continues on aerosol transmission [3–5].Cystic Fibrosis (CF) is a genetic disorder affecting multiple organs, including the pancreas, hepatobiliary system and reproductive organs however lung disease is responsible for the majority of morbidity and mortality. Management of CF involves CFTR modulator agents including corrector drugs to augment cellular trafficking of mutant CFTR as well as potentiators that open defective CFTR channels. These therapies are poised to help most individuals with CF, with the notable exception of individuals with class I mutations where full length CFTR protein is not produced. For these mutations, gene replacement has been suggested as a potential solution.In this work, we used a helper dependent adenoviral vector (HD-CFTR) to express CFTR in nasal epithelial cell cultures derived from CF subjects with class I CFTR mutations. CFTR function was significantly restored in CF cells by HD-CFTR and reached healthy control functional levels as detected by Ussing chamber and membrane potential (FLIPR) assay. A dose response relationship was observed between the amount of vector used and subsequent functional outcomes; small amounts of HD-CFTR were sufficient to correct CFTR function. At higher doses, HD-CFTR did not increase CFTR function in healthy control cells above baseline values. This latter observation allowed us to use this vector to benchmark in vitro efficacy testing of CFTR-modulator drugs. In summary, we demonstrate the potential for HD-CFTR to inform in vitro testing and to restore CFTR function to healthy control levels in airway cells with class I or CFTR nonsense mutations.MicroRNAs (miRs) have been shown to disrupt normal lung development and function by interrupting alveolarization and vascularisation leading to development of bronchopulmonary dysplasia (BPD). Here we report that miR-184 has a critical role in the induction of BPD phenotype characterised by abnormal alveolarization and pulmonary angiogenesis in the developing lung. link3 We observed an increased expression of miR-184 in BPD clinical specimens tracheal aspirates (TA), human neonatal lungs with BPD and in fetal human lung Type II alveolar epithelial cells (TIIAECs) exposed to hyperoxia. Consistent with this, we also detected an upregulated miR-184-3p expression in whole lungs, in freshly isolated TIIAECs from lungs of hyperoxia-induced experimental BPD mice and in fetal mice lung TIIAECs exposed to hyperoxia. We demonstrate that overexpression of miR-184-3p exacerbates the BPD pulmonary phenotype, while downregulation of miR-184-3p expression ameliorated the BPD phenotype and also improved respiratory function. We identified miR-184 specific targets platelet-derived growth factor-beta (Pdgf-β) and friend of Gata 2 (Fog2), also known as zinc finger protein family member (Zfpm2), and show that they are critically involved in pulmonary alveolarization and angiogenesis.
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