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BackgroundUncertainty over the therapeutic benefit provided by parenteral remdesivir in COVID-19 has resulted in varying treatment guidelines. Early in the pandemic the monoclonal antibody cocktail, casirivimab/imdevimab, proved highly effective in clinical trials but because of weak or absentin vitroactivity against the SARS-CoV-2 Omicron BA.1 subvariant, it is no longer recommended.MethodsIn a multicenter open label, randomized, controlled adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to one of eight treatment arms including intravenous remdesivir (200mg followed by 100mg daily for five days), casirivimab/imdevimab (600mg/600mg), and no study drug. The primary outcome was the viral clearance rate in the modified intention-to-treat population derived from daily log10viral densities (days 0-7) in standardized duplicate oropharyngeal swab eluates. This ongoing adaptive trial is registered atClinicalTrials.gov(NCT05041907).ResultsAcceleration in mean estimated SARS-CoV-2 viral clearance, compared with the contemporaneous no study drug arm (n=64), was 42% (95%CI 18 to 73%) for remdesivir (n=67). Acceleration with casirivimab/imdevimab was 58% (95%CI: 10 to 120) in Delta (n=13), and 20% (95%CI: 3 to 43) in Omicron variant (n=61) infections compared with contemporaneous no study drug arm (n=84). In apost hocsubgroup analysis viral clearance was accelerated by 8% in BA.1 (95%CI: −21 to 59) and 23% (95%CI: 3 to 49) in BA.2 and BA.5 Omicron subvariants.ConclusionsParenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Despite substantially reducedin vitroactivities, casirivimab/imdevimab retainsin vivoantiviral activity against COVID-19 infections caused by currently prevalent Omicron subvariants.Brief summaryIn early symptomatic COVID-19 remdesivir accelerated viral clearance by 42% while the monoclonal antibody cocktail casirivimab/imdevimab accelerated clearance by approximately 60% in SARS-CoV-2 Delta variant infections, and by approximately 25% in infections with Omicron subvariants BA.2 and BA.5.

Introduction Recurrence of atrial fibrillation (AF) after catheter ablation (CA) is estimated to be between 20% and 45% and the prediction of recurrence AF in patients (pts) with paroxysmal AF undergoing CA remains challenging. Purpose To determine the clinical and procedural predictors of recurrence AF after CA in pts with paroxysmal AF. Methods Single-centre retrospective study that included all pts with paroxysmal AF who underwent AF CA between 2017 and 2019. Ablation procedures included radiofrequency and second-generation cryoballoon CA. All pts underwent cardiac computed tomography prior the procedure. AF recurrence was defined as any recurrence of AF, atrial flutter or atrial tachycardia >30 seconds (recorded in 12-lead electrocardiogram or Holter) after 90 days of CA. The independent association between clinical and procedural variables and AF recurrence was evaluated with Cox regression analysis. Results We included 351 pts, 63,5% male and with a mean age of 57,1±11,4 years. CHADSVASCscore ≥2 points were present in 43,7% of the pts, median duration of AF prior the intervention was 3 years (IQR 1–6) and most pts were treated with some antiarrhythmic drug at the time of CA (56,9%). Overall, median follow-up was 27 months (IQR 19–39). AF recurrence was present in 96 pts (27,4%), on average, 15,2±10,4 months after CA. Univariate logistic regression identified female gender, thyroid disease, left atrium (LA) enlargement (defined as LA indexed volume >34 mL/m2 or LA diameter >38mm for female or >40mm for male), coronary calcium score >100, epicardial adipose tissue volume, number of previous electric cardioversions, treatment with antiarrhythmic drugs prior CA and the extent of CA (only pulmonary vein isolation (PVI) or PVI and ablation of other lesions) as predictors of recurrence AF after CA in pts with paroxysmal AF (p Cox regression analysis identified female gender (OR 1,615, 95% CI 1,005–2,597; p=0,008), LA enlargement (OR 2,084, 95% CI 1,207–3,596; p=0,008) and coronary calcium score >100 (OR 1,958, 95% CI 1,133–3,385; p=0,016) as independent predictors of AF recurrence. Conclusions In our cohort, AF recurrence was significantly higher in pts with LA enlargement, with coronary calcium score >100 and female gender pts. Funding Acknowledgement Type of funding sources: None.

Background Among patients with an aborted episode of malignant ventricular arrhythmias without a reversible cause, the Implantable Cardioverter Defibrillator (ICD) is considered an important therapy for secondary prevention of sudden cardiac death (SCD). Some authors propose primary catheter ablation and deferred ICD implantation may be the preferred approach in patients with substrate-related ventricular tachycardia. Purpose We want to evaluate the need of secondary time ablation in patients with secondary prevention ICD, when submitted only a medical therapy after the index event. Methods We conducted a retrospective, observational study of 90 patients who consecutively implanted ICD after an aborted episode of malignant ventricular arrhythmias without a reversible/known cause between 2014 and 2020. Patients with Brugada Syndrome, Wolff-Parkinson-White syndrome, QT related diseases and previous ventricular tachycardia (VT) ablation were excluded. Baseline clinical characteristics were analyzed, and a 1-year follow-up was performed: cardiovascular (CV) death, sustain VT), ventricular fibrillation (VF), antitachycardia pacing (ATP), ICD shock, VT ablation. Results Mean age was 58±18 years, 80% (n=72) were male and 65.5% (n=59) had a non-ischemic etiology. Most of the patients (61%; n=56) present with hemodynamic unstable VT or syncope, and 38% (n=34) with SCD [most due to VF (n=30)]. After the index event 41.1% (n=37) and 83.8% (n=75) initiate antiarrhythmic and beta-blocker (BB), respectively. During 1-year follow-up (FUP) 11.1% (n=10) had a sustain VT and 2.2% (n=2) VF leading to ATP and appropriated shock in 11.1% (n=10) and 10% (n=9), respectively. There was 2 CV death [due to acute heart failure (HF)], 8 HF hospitalization and 3 VT ablation during follow-up. The presence of chronic kidney disease at baseline was the only parameter related to 1-year CV death (1.3% vs 18.2%, p=0.039) and HF hospitalization (0% vs 18.2%, p=0.014). The antiarrhythmic after index event was associated with a significant less sustain VT [10% vs 45%, OR 0.114 (IC 95% 0.014 to 0.927] and consequently ATP (adjusted for age) and had a numerical benefit in ICD shock (2.7% vs 15.1%, p=0.076) and need of a secondary time ablation (0% vs 5.7%, p=0.266). Conclusion The ICD implant with antiarrhythmic therapy, as a primary approach to secondary prevention (vs ablation), after an aborted episode of malignant ventricular arrhythmias still showed to be a secure and viable first option. Funding Acknowledgement Type of funding sources: None.

Left atrial ejection fraction (LAEF) has been previously shown to accurately distinguish between patients with and without clearly defined left ventricle diastolic dysfunction (LVDD) by ASE/EACVI criteria, but indeterminate cases were excluded. We sought to determine if LAEF could accurately distinguish between normal, indeterminate and LVDD patients. A retrospective cohort of 125 patients who underwent transthoracic echocardiography was studied. Comprehensive echocardiographic study was performed with measurement of validated diastolic parameters. Subjects were assigned LVDF ASE/EACVI categories. ANOVA test was used to compare means between groups and binary logistic regression and ROC curves to assess diagnostic accuracy. Mean LAEF was statistically different between groups (p

BACKGROUND The brief-access taste aversion (BATA) model has been used as an alternative taste assessment tool to human taste panels and became an important element of pharmaceutical drug development, especially regarding pediatric patient's compliance. This model has been validated, demonstrating a concentration-dependent sensitivity to drug aversiveness, as well as the capacity to evaluate the taste-masking effects of cyclodextrins. In the BATA model, samples are presented randomly to rodents in numerous sipper tubes and a lickometer is used for the electronic record of licks in a sophisticated approach. OBJECTIVES The aim of this study was to test possible drug taste-masking strategies. Additionally, we have used an alternative approach to measure the animal lick number in the presence of different compounds, non-simultaneously. RESULTS In the present work we show for the first time the licking profile of different compounds during the time course of the experiment, with each animal being exposed to only one bottle of testing product. To validate the experiments, quinine hydrochloride dihydrate (QHD) was used as a bitter reference compound. CONCLUSION The results obtained using this simple approach showed that aversiveness is dependent on the assay duration, and that it is possible to predict the aversiveness just by measuring the mass of the tested substance consumption. Moreover, some taste-masking strategies, such as those used in pediatric formulations and corresponding to the addition of sweeteners or flavors, cannot be predicted from rodents BATA model.

Background. Exercise is increasingly becoming recognized as an important adjunct to medications in the clinical management of Parkinson’s disease (PD). Boxing and sensory exercise have shown immediate benefits, but whether they continue beyond program completion is unknown. This study aimed to investigate the effects of boxing and sensory training on motor symptoms of PD, and whether these benefits remain upon completion of the intervention. Methods. In this 20-week double-blinded randomized controlled trial, 40 participants with idiopathic PD were randomized into 2 treatment groups, (n = 20) boxing or (n = 20) sensory exercise. Participants completed 10 weeks of intervention. Motor symptoms were assessed at (week 0, 10, and 20) using the Unified Parkinson’s Disease Rating Scale (UPDRS-III). Data were analyzed using SPSS, and repeated-measures ANOVA was conducted. Results. A significant interaction effect between groups and time were observed F(1, 39) = 4.566, P = .036, where the sensory group improved in comparison to the boxing group. Post hoc analysis revealed that in comparison to boxing, the effects of exercise did not wear off at washout (week 20) P < .006. Conclusion. Future rehabilitation research should incorporate similar measures to explore whether effects of exercise wear off post intervention.

Contains fulltext : 238527.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is not clear how specific gait measures reflect disease severity across the disease spectrum in Parkinson's disease (PD). OBJECTIVE: To identify the gait and mobility measures that are most sensitive and reflective of PD motor stages and determine the optimal sensor location in each disease stage. METHODS: Cross-sectional wearable-sensor records were collected in 332 patients with PD (Hoehn and Yahr scale I-III) and 100 age-matched healthy controls. Sensors were adhered to the participant's lower back, bilateral ankles, and wrists. Study participants walked in a ~15-meter corridor for 1 minute under two walking conditions: (1) preferred, usual walking speed and (2) walking while engaging in a cognitive task (dual-task). A subgroup (n = 303, 67% PD) also performed the Timed Up and Go test. Multiple machine-learning feature selection and classification algorithms were applied to discriminate between controls and PD and between the different PD severity stages. RESULTS: High discriminatory values were found between motor disease stages with mean sensitivity in the range 72%-83%, specificity 69%-80%, and area under the curve (AUC) 0.76-0.90. Measures from upper-limb sensors best discriminated controls from early PD, turning measures obtained from the trunk sensor were prominent in mid-stage PD, and stride timing and regularity were discriminative in more advanced stages. CONCLUSIONS: Applying machine-learning to multiple, wearable-derived features reveals that different measures of gait and mobility are associated with and discriminate distinct stages of PD. These disparate feature sets can augment the objective monitoring of disease progression and may be useful for cohort selection and power analyses in clinical trials of PD. © 2021 International Parkinson and Movement Disorder Society.

ObjectiveTympanostomy is one of the most commonly performed surgical procedures in otolaryngology, and its complexity is challenging for trainee surgeons. Investing in medical education is a cornerstone of good patient safety practices. For trainees, use of simulators before operating on actual patients helps mitigate risks. This study aimed to develop a three-dimensional printed model simulator for myringotomy, tympanostomy and ventilation tube placement.MethodsAn articulated model with a detachable portion, base and plastic bag to simulate the external auditory canal, middle ear and tympanic membrane, respectively, was modelled and printed.ResultsThe final simulator was made from acrylonitrile butadiene styrene polymer and measured 4 × 4 × 12 cm. It was designed to mimic the angulation of patient anatomy in the myringotomy position and simulate the texture and colour of the tissues of interest. The cost was low, and testing with an operating microscope and endoscope yielded satisfactory results. The advent of three-dimensional printing technology has made surgical simulation more accessible and less expensive, providing several advantages for medical education.ConclusionThe proposed model fulfilled expectations as a safe, inexpensive, reproducible, user-friendly and accessible surgical education tool that can be improved and reassessed for further research.

Introduction Poor sleep quality and chronic pain are common after moderate-to-severe traumatic brain injury (msTBI). Prior studies have not examined the role of PTSD symptoms in the relationship between sleep quality and chronic pain experience (i.e., severity and pain-related interference) in those with msTBI. Yet, PTSD is known to be associated with both sleep and pain. The purpose of this analysis is to determine the role of PTSD symptoms in the sleep-pain relationship among this at-risk clinical population. Methods Secondary analyses were performed on data (n=1537) from the TBI Model Systems follow-up study. Participants were an average age of 46.21 years old, predominantly male (72.61%), and followed at an average of 8.5 years post injury. Participants completed measures of sleep quality (Pittsburgh Sleep Quality Index; PSQI), pain severity and interference (Brief Pain Inventory; BPI), depression (Patient Health Questionnaire-9; PHQ-9) and PTSD symptoms (PTSD Checklist, PCL-5). Analysis of covariance (ANCOVA) was used to examine differences in pain outcomes controlling for relevant covariates, adjusting for item redundancy prior to analyses. Results Sleep quality and pain interference are associated such that “good sleepers” (PSQI≤8, mean=4.92±2.17) have lower pain interference scores than “poor sleepers” (PSQI>8, mean=12.63±2.87), with a mean pain interference of 3.41±2.32 vs 5.26±2.45 (p< 0.0001). “Good sleepers” also had lower pain severity (4.22±1.78 vs 5.28±1.84, p< 0.0001), lower PTSD symptoms (14.62±13.46 vs 28.35±17.82, p< 0.0001), and less depression symptoms (5.32±4.97 vs 10.57±6.22, p< 0.0001) when compared to “poor sleepers.” Pain interference and severity were significantly related to all covariates at a Conclusion In patients with msTBI, sleep quality and pain interference are positively associated such that better sleep quality corresponds with lower pain interference, a relationship which remains when controlling for PTSD and multiple covariates. Addressing the sleep needs of patients with msTBI through behavioral intervention (e.g., cognitive behavioral therapy for insomnia), even in the presence of additional psychiatric comorbidities, may assist those who experience chronic pain following injury. Support (if any)

Introduction Previous studies have shown automatic scoring of portable level 3 sleep study provides similar findings when compared to polysomnography (PSG), establishing home sleep apnea tests (HSAT) as an adequate screening tool for OSA. Accuracy of level 3 studies with Nox T3 portable sleep studies (Noxturna Inc., Atlanta GA) may improve with manual editing to include total sleep time (TST). No other studies have compared unedited versus manually edited HSAT with level 1 in-lab PSG performed simultaneously. This study evaluates if added manual editing optimizes the diagnostic accuracy of HSAT in classifying the severity of OSA, using both AASM and CMS criteria. Methods Secondary analysis of six-center (n=206) sleep apnea diagnostic comparative effectiveness trial. Participants underwent simultaneous administration of level 1 PSG (Philips Alice 6 LDx Diagnostic Sleep system) and Nox T3 portable sleep study with centralized scoring using AASM and CMS criteria. All HSAT were autoscored and then edited by the registered polysomnographic technician. Editing entailed establishing start and stop recording times based on accompanying actigraphy data (reduction in movement) in the portable device and elimination of recording artifact. Results Using AASM criteria, poor sensitivity OSA (AHI≥5) was observed using unedited vs PSG (p=.01) compared to manually edited HSAT vs. PSG (p=.06). No statistically significant difference was observed using AHI≥15 or via categorization across four levels of OSA (none, mild, moderate, or severe). In contrast, CMS criteria comparisons to PSG showed poor specificity of OSA (AHI≥5) for unedited (p=.003) compared to edited (p=.372) HSAT studies. As expected, total sleep time was overestimated using T3 actigraphy devices compared to the criterion standard across both edited and unedited studies (p=.001, .001 respectively). Conclusion Improvements in sensitivity and specificity of OSA were noted using edited versus unedited T3 HSAT when compared to Level 1 PSG using both AASM and CMS criteria. Results support need for manualized editing of HSAT in persons with hospitalized TBI. Support (if any) PCORI (CER-1511-33005), GDHS (W91YTZ-13-C-0015)

Introduction Gait impairment is common in neurodegenerative disorders. Specifically, gait variability—the stride‐to‐stride fluctuations in distance and time—has been associated with neurodegeneration and cognitive impairment. However, quantitative comparisons of gait impairments across the cognitive spectrum of dementias have not been systematically investigated. Methods Older adults (N = 500) with subjective cognitive impairment, Parkinson disease (PD), mild cognitive impairment (MCI), PD‐MCI, Alzheimer's disease (AD), PD‐dementia, Lewy body dementia, and frontotemporal dementia, as well cognitive normal controls, who were assessed for their gait and cognitive performance. Results Factor analyses grouped 11 quantitative gait parameters and identified four independent gait domains: rhythm, pace, variability, and postural control, for group comparisons and classification analysis. Among these domains, only high gait variability was associated with lower cognitive performance and accurately discriminated AD from other neurodegenerative and cognitive conditions. Discussion Our findings indicate that high gait variability is a marker of cognitive‐cortical dysfunction, which can help to identify Alzheimer's disease dementia.

A mobilidade ciente de contexto tem o potencial de tornar a maneira como nos deslocamos mais eficiente, segura e sustentável. Dentre os contextos possíveis, a segurança, em termos de níveis de criminalidade das regiões, é um que tem sido utilizado visando o cálculo de rotas mais seguras. Porém, os trabalhos existentes focam em veículos particulares, e não avaliam o impacto gerado para os cidadãos como um todo. Neste trabalho, uma solução existente para o cálculo de rotas seguras é avaliada no contexto de transporte coletivo de ônibus em termos do impacto causado para os passageiros. Os resultados mostraram que, em geral, a mudança de uma rota de ônibus para se tornar mais segura aumenta o trecho viajado em poucos quilômetros para a maioria dos passageiros. Além desta análise, uma ferramenta para extração de fluxos de mobilidade escalável foi também implementada como contribuição do trabalho.

Chronic inflammation can remain many years after the completion of cancer treatment and is associated with cancer recurrence. The purpose of this study was to examine how a 16-week therapeutic yoga program (TYP) modulates the cytokine profile in heterogeneous cancer survivors.Eligible participants were 18 years of age or older and clinically diagnosed with cancer. Consenting participants were asked to attend three, 75-min sessions weekly of TYP with meditation. Seventeen patients provided blood samples at baseline and end of study. Eight cytokines (interferon (IFN)-γ; interleukin (IL)-1b, IL-1ra, IL-4, IL-6, IL-8, IL-10; and tumor necrosis factor (TNF)-α), three receptors (sIL-6R, sTNFRI, sTNFRII), and C-reactive protein (CRP) were quantified.Patients were 59.6 ± 7.3 years old; over half (56%) were overweight or obese BMI ≥ 25 kg/mTYP led to significant reduction in circulating cytokines associated with chronic inflammation in a heterogeneous sample of cancer survivors.

Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future.

Lemierre's syndrome refers to infectious thrombophlebitis of the internal jugular vein developed as complication of an oropharyngeal infection. It is a rare syndrome, affecting otherwise healthy young adults, which may lead to sepsis complicated by septic embolization. Although there is a characteristic clinical picture, many modern physicians are unaware of this syndrome, leading it to be termed ‘the forgotten disease’. The authors report a case of late diagnosis due to initial suspicion of COVID-19 and highlight the pitfalls on its diagnosis., Portuguese Journal of Cardiac Thoracic and Vascular Surgery, Vol. 29 No. 2 (2022): Apr-Jun

Funding Acknowledgements Type of funding sources: None. Background Malnutrition had been associated with worse prognosis in heart failure (HF) patients, especially in elder. However, this association wasn’t demonstrated in coronary patients, after a ST-segment elevation myocardial infarction (STEMI). We want to evaluate the prognosis value of malnutrition, in elder patients, after a STEMI. Methods We conducted a retrospective, observational study of 200 elderly patients (365 years) consecutively admitted with STEMI between 2016 and 2017. At discharge, we applied a validated formula who evaluate nutritional status: "Prognostic Nutritional Index" (PNI), [10 x serum albumin at discharge (g/dL) + 0.005 x total lymphocytes at discharge], whose lowest values were associated with malnutrition. At 1 year follow-up, we evaluated the relation between PNI and major adverse cardiac events (MACE): myocardial infarction (MI), HF hospitalization, cardiovascular (CV) and all-cause death. Results Mean age was 74±8 years, 71% (n=149) were male and with multiples risks factors (75% hypertense, 63% with dyslipidemia, 33% diabetes and 11% smokers). At discharge, patients had a mean Left Ventricular Ejection Fraction (LVEF) of 47±8% and a mean PNI of 37±5. Low PNI values (malnutrition) were significant associated with MACE at 1-year [OR 0.87 (95% CI 0.78 to 0.97, p=0.01)], after adjusting for age, sex and LVEF. When evaluated individually, low PNI was associated with more incidence of 1-year HF hospitalization [OR 0.88 (95% CI 0.78 to 0.99, p=0.03)] and all-cause death [OR 0.84 (95% CI 0.75 to 0.95, p=0.004)], after adjusting for age, sex and LVEF, but not with MI and CV death. Conclusion Malnutrion associated with other comorbidities inherent to elderly people were associated with MACE, 1-year after STEMI, in this type of population. Thus, we want to draw attention to the importance of evaluating the nutritional status during hospitalization for STEMI, allowing to initiate measures that contribute to its improvement.

It is reported here a large improvement in numerically calculated TEM00-mode side-pumped solar laser efficiency, and brightness figure-of-merit by pumping two thin Nd:YAG laser rods simultaneously with a ring-array solar energy primary concentrator. Two side-pumping configurations were investigated. A single-rod configuration was used to pump a typical single thick laser rod with the full collection area of the ring-array concentrator, and a dual-rod to pump two thin laser rods simultaneously. A three-folding-mirror laser beam merging technique was used, enabling the emission of only one laser beam from the two rods. For the dual-rod single laser beam configuration, 27.50 W continuous-wave TEM00-mode solar laser output power was numerically achieved, corresponding to 16.10 W/m2 TEM00-mode solar laser collection efficiency, 1.70% solar-to-laser power conversion efficiency, 25.00 W brightness figure-of-merit, and 1.54% brightness conversion efficiency, being 1.46, 1.30, 1.75, and 1.40 times, respectively, higher than the previous numerical records, and also 2.04, 1.60, 3.87, and 2.03 times, respectively, more than the previous state-of-the-art experimental records.

RationaleExhaled breath condensate (EBC) promises a valuable, non-invasive, and easy to obtain clinical sample. However, it’s not currently used diagnostically due to poor reproducibility, sample contamination, and sample loss.ObjectiveWe evaluated whether a new, hand-held EBC collector (PBM-HALETM) that separates inertially impacted large droplets (LD) before condensing fine aerosols (FA) in distinct, self-sealing containers, overcomes current limitations.MethodsSampling consistency was determined in healthy volunteers by microbial culture, 16S phylogenetics, spectrophotometry, RT-PCR, and HILIC-MS. Capture of aerosolised polystyrene beads, liposomes, virus-like particles, or pseudotyped virus was analysed by nanoparticle tracking analysis, reporter expression assays, and flow cytometry. Acute symptomatic COVID-19 case tidal FA EBC viral load was quantified by RT-qPCR. Exhaled particles were counted by laser light scattering.Measurements and Main ResultsSalivary amylase-free FA EBC capture was linear (R2=0.9992; 0.25-30 min) yielding RNA (6.03 μg/mL) containing eukaryotic 18S rRNA (RT-qPCR; pStreptococcus enrichment in a mild dry cough case. Nebulized pseudotyped virus infectivity loss ConclusionsHigh purity, distal airway FA EBC can reproducibly and robustly inform contamination-free infectious agent emission sources, and be quantitatively assayed for multiple host, microbial, and lifestyle biomarker classes.

Funding Acknowledgements Type of funding sources: None. Background Neurocardiogenic syncope (NCS) is the most frequent aetiology of syncope in young people. Cardioinhibition with asystole and/or transitory atrio-ventricular block induced by a massive vagal reflex is commonly observed in severe cases. According to the current guidelines, cardiac pacing is indicated in patients > 40 years old with severe, recurrent syncope and documented cardioinhibitory reflex. In younger patients there is no recommendation. Although pacing therapy could be effective, complications after pacemaker implantation are commonly seen. Recently, cardioneuroablation (CNA), a technique based on radiofrequency ablation of vagal ganglia, was developed to treat NCS as an alternative to pacemaker implantation in younger patients. However, this method is still evolving, and existing data refer to a small number of patients in a limited number of centres. Purpose The aim of our study was to evaluate the efficacy and safety of CNA in patients with highly symptomatic neurocardiogenic syncope. Methods and Results A total of 15 patients (11 male; aged 40.0 ± 13.3 years) who underwent CNA in two Portuguese centres between January 2019 and September 2021 were included. All had recurrent syncope with documented pauses at head-up tilt test, Holter or implantable loop recorder. Radiofrequency energy was applied in ganglionated plexi (GP) 1 (between the right upper pulmonary vein and the right atrium) in 14 patients, GP2 (between the superior vena cava and aortic root just above the right upper pulmonary vein) in 9 patients, GP3 (between the inferior vena cava and the right and left atrium) in 5 patients and GP4 (at the insertion of the left pulmonary veins) in 9 patients. The end point of procedure was the inhibition of the vagal response at target sites. Ablation was successfully performed in all patients. One patient had a convulsive episode after the procedure, requiring admission to intensive care but without neurological sequelae. No other major complications occurred. At a mean follow-up of 17.1 ± 12.6 months (range 3-35 months), 13 patients remained free of syncope. Other 2 patients had spontaneous recurrence of syncope (both 9 months after CNA) and underwent a new procedure. These 2 patients had a new symptomatic recurrence and a pacemaker was implanted. Conclusion CNA appears to be an effective and safe treatment option for patients with refractory neurocardiogenic syncope and provide a new potential approach without pacemaker implantation.

Funding Acknowledgements Type of funding sources: None. Introduction Patients with atrial fibrillation (AF) referred for catheter ablation routinely undergo cardiac computed tomography (CCT) for procedure planning. An opportunistic evaluation of coronary artery calcium score (CACS) can be an important tool to improve clinical care. It is already known that CACS is associated with a high risk of AF development, particularly if values are above 100, but few data are available regarding the impact of CACS in AF recurrence after ablation. Purpose To assess the impact of CACS on atrial fibrillation recurrence following catheter ablation. Methods Retrospective, single-centre cohort study of consecutive patients with AF undergoing CCT for ablation procedure planning, from 2017 to 2019. Baseline clinical and demographical data were collected. Patients with known history of coronary artery disease (CAD) and moderate to severe valvular heart disease were excluded. CACS was assessed using the Agatston method. Recurrence was defined as any documented episode of AF, atrial flutter or atrial tachycardia after 3 months from procedure. Patients were stratified in CACS Results A total of 354 patients were included, with a mean age of 56 ± 12 years, 66% male and 21% with persistent AF. More than half of the patients had a CACS>0 (n=185, 52%) and 63 patients (18%) had a CACS≥100. Patients with CACS≥100 were older (63 ± 7 vs 54 ± 12 years, p CACS≥100 was associated with increased risk of AF recurrence (unadjusted Cox regression: hazard ratio [HR] 1.85; 95% confidence interval [CI], 1.23-2.79, p=0.003) (Fig. 1). After covariate adjustment (age, gender, hypertension, diabetes mellitus, obesity, thyroid disease, AF type and left atria enlargement) CACS≥100 remained an independent predictor of the risk of AF recurrence (HR, 1.68; 95% CI, 1.05-2.70, p=0.03) as well as persistent AF (HR, 1.91; 95% CI, 1.23-3.00, p=0.004) (Fig. 2). Conclusion In patients with AF undergoing catheter ablation, without previous history of CAD, a CACS≥100 was independently associated with a 68% increase in the risk of AF recurrence.

Funding Acknowledgements Type of funding sources: None. Introduction Both coronary artery calcium (CAC) and epicardial adipose tissue (EAT) had been implicated in coronary artery disease (CAD) and risk of future adverse cardiovascular events. There are scarce data regarding the assessment and association of EAT volume and CAC score (CACS) in atrial fibrillation (AF) patients. Purpose To assess the association between EAT volume and the presence and severity of CAC in patients with AF. Methods Retrospective and single-centre study including consecutive patients with AF undergoing contrast-enhanced cardiac computed tomography for catheter ablation planning, from 2017 to 2019. Patients with known history of CAD and moderate to severe valvular heart disease were excluded. Baseline clinical and demographical data were collected, as well as their cardiovascular risk, based on the SCORE (Systematic Coronary Risk Evaluation) system and cardiovascular risk categories. We assessed CACS (Agatston method) and EAT volume and analysed their association. EAT was defined as the adipose tissue accumulated between the visceral pericardium and the myocardium and was semi-automatically reconstructed by manually tracing the pericardium. Patients were split into three groups according to CACS: 0, 1-99 and ≥100. A logistic regression (LR) analysis was performed to explore the relationship between EAT volume and the presence of CAC (CACS>0), adjusted for age, gender, obesity, diabetes mellitus and hypertension. Results A total of 354 patients were included, with a mean age of 56 ± 12 years, 66% male and 21% with persistent AF. A CHA2DS2-VASc score ≥2 was present in 130 (37%) patients and most patients had low to moderate cardiovascular risk (n=213, 82%). More than half of the patients had a CACS>0 (n=185, 52%), of which 63 patients (18%) had a CACS≥100. The mean EAT volume was 79 ± 39 ml. There was a significant association between EAT volume and the presence of CAC: CACS=0 69 ± 34 ml vs CACS 1-99 84 ± 38 ml vs CACS ≥100 95 ± 45 ml (p Conclusion In our cohort of patients with AF undergoing catheter ablation we observed an association between EAT and CACS. Nevertheless, EAT volume was not an independent predictor of CACS and only the classical cardiovascular risk factors remained significant.

Funding Acknowledgements Type of funding sources: None. Background Several studies have demonstrated the relation between general obesity and atrial fibrillation (AF). Epicardial adipose tissue (EAT), due to its local paracrine effect and the intimate relation with the atrium, could influence AF recurrence rates, but very few studies have explored this association. Purpose In this study we aimed to evaluate if EAT could be a predictor of AF recurrence after an AF ablation procedure. Methods We included all consecutive patients submitted to AF ablation (2017-2019) who performed a computed tomography scan prior to the procedure. EAT volume was semi-automatically reconstructed by manually tracing the pericardium. Adipose tissue was defined in the range between -150 and -50 Hounsfield units. Recurrence was defined as any documented (ECG/Holter) episode of AF, atrial flutter or atrial tachycardia after 3 months of the procedure. Logistic regression with a restricted cubic polynomial transformation was used to model the non-linear relationship between recurrence and EAT volumes. Inspection of the partial effect curves suggested that a cutoff for EAT volume ≥80mL could stratify patients at risk of recurrence and a Time-to-event analysis was carried. Results A total of 354 patients (66% male, median age 57 years [IQR 48–65] and 21% persistent AF) were included. During a median follow-up of 34 months [IQR 24-43], 117 patients (33%) had AF recurrence. These patients had a significantly greater EAT volume (76 mL [IQR 55-111] vs 72 mL [IQR 48-95], p=0.03) when compared to those without recurrence. Also, patients with higher EAT volume (≥ 80mL) had a higher risk of recurrence compared to patients with lower volume (Figure 1, log-rank test p=0.007). After adjusting for clinical risk factors (age, gender, hypertension, diabetes mellitus, obesity, thyroid disease, AF type and left atrial enlargement), higher EAT volume did not remain an independent predictor of AF recurrence (Figure 2, HR 1.25 [95% CI, 0.83-1.86] p=0.3). Conclusion In this cohort of patients with AF submitted to catheter ablation, EAT volume ≥80mL was associated with increased risk of AF recurrence. However, it was not an independent predictor of AF recurrence after adjustment to clinical risk factors.

Funding Acknowledgements Type of funding sources: None. Background In frail elderly patients or when atrioventricular block (AVB) is paroxysmal, and pacing anticipated to be infrequent, single chamber pacing (VVI or VDD) may be considered as it carries a lower complication rate compared with DDD devices. For sinus rhythm patients, the single lead VDD, by preserving atrial sensing, is a more physiological mode than VVI devices, with comparable time procedure and complication rates. However, there are few data assessing the performance of VDD pacemakers in elderly patients, with AVB and sinus rhythm. Purpose We want to evaluate the 3-years performance of VDD pacemakers (PM) in frailty elder patients with AVB. Methods We conducted a retrospective, observational study of 200 elderly (³75 years) patients with AVB and normal sinus rhythm who consecutively implanted VDD PM between 2016 and 2018. Baseline clinical characteristics were analyzed, and a 3-years follow-up was performed: atrial undersensing, atrial fibrillation (AF), heart failure (HF) hospitalization, cardiovascular (CV) and non-CV death. Results Mean age was 84±5 years and 55% were female. The study population presented several comorbidities: 74% had atrial hypertension, 49% dyslipidemia, 35% chronic kidney disease and 28% diabetes. After 3-years follow-up most of the patients (90%; n=162) were still programmed in their original mode with good atrial sensing. Due to permanent AF, 4%(n=8) patients had been switched to VVIR mode and 5.5% (n=11) due to P-wave undersensig. 0ne-third (n=65) died during follow-up, 89% (n=58) due to non-CV causes. Low amplitude P-wave ( Conclusion A significantly larger number of VDD-paced elderly patients maintain their original mode program with good atrial sensing. Moreover, atrial undersensing did not influence mortality or HF hospitalization rate. These results reinforce the benefit of VDD use among frail and elderly patients.

SUMMARYThe shaping of bone structures relies on various cell types and signalling pathways. Here, we use the zebrafish bifurcating fin rays during regeneration to investigate bone patterning. We found that the regenerating fin rays form via two mineralization fronts that undergo an osteoblast-dependent fusion/stitching until the branchpoint, and that bifurcation is not simply the splitting of one unit into two. We identified tartrate-resistant acid phosphatase-positive (TRAP+) osteolytic tubular structures at the branchpoints, here named osteolytic tubules (OLTs). Chemical inhibition of their bone-resorbing activity strongly impairs ray bifurcation, indicating that OLTs counteract the stitching process. Finally, by testing different osteoactive compounds, we show that the position of the branchpoint depends on the balance between bone mineralization and resorption activities. Overall, these findings provide a new perspective on fin ray formation and bifurcation, and reveal a key role for OLTs in defining the proximo-distal position of the branchpoint.Graphical summary

Resumo Fundamento Ainda não está estabelecido se a captação de fluorodesoxiglicose no miocárdio ocorre exclusivamente por características fisiológicas ou se representa um desarranjo metabólico causado pela quimioterapia. Objetivo Investigar os efeitos da quimioterapia no coração dos pacientes com linfoma por tomografia por emissão de pósitrons associada a tomografia computadorizada (PET/CT) com 2-[18F]-fluoro-2-desoxi-D-glicose (18F-FDG PET/CT) antes, durante e/ou após a quimioterapia. Métodos Setenta pacientes com linfoma submetidos a 18F-FDG PET/CT foram retrospectivamente analisados. O nível de significância foi de 5%. A captação de 18F-FDG foi avaliada por três medidas: captação máxima no ventrículo esquerdo ( standardized uptake value , SUV max), razão SUV cardíaco / aorta e SUV cardíaco / SUV no fígado. Também foram comparados peso corporal, glicemia de jejum, tempo pós-injeção e dose administrada de 18F-FDG entre os exames. Resultados A idade média foi de 50,4 ± 20,1 anos e 50% dos pacientes eram mulheres. A análise foi realizada em dois grupos – PET/CT basal vs. intermediário e PET/CT basal vs pós-terapia. Não houve diferença significativa entre as variáveis clínicas e do protocolo dos exames entre os diferentes momentos avaliados. Nós observamos um aumento na SUV máxima no ventrículo esquerdo de 3,5±1,9 (basal) para 5,6±4,0 (intermediário), p=0,01, e de 4,0±2,2 (basal) para 6,1±4,2 (pós-terapia), p

Optical fiber sensing systems have been widely developed for several fields such as biomedical diagnosis, food technology, military and industrial applications and civil engineering. Nowadays, the growth and advances of optical fiber sensors (OFS) are focused on the development of novel sensing concepts and transducers as well as sensor cost reduction. This review provides an overview of the state-of-the-art of OFS based on sol–gel materials for diverse applications with particular emphasis on OFS for structural health monitoring of concrete structures. The types of precursors used in the development of sol–gel materials for OFS functionalization to monitor a wide range of analytes are debated. The main advantages of OFS compared to other sensing systems such as electrochemical sensors are also considered. An interdisciplinary review to a broad audience of engineers and materials scientists is provided and the relationship between the chemistry of sol–gel material synthesis and the development of OFS is considered. To the best of the authors’ knowledge, no review manuscripts were found in which the fields of sol–gel chemistry and OFS are correlated. The authors consider that this review will serve as a reference as well as provide insights for experts into the application of sol–gel chemistry and OFS in the civil engineering field.

In the global context of emerging pathogens associated with respiratory diseases, novel nanostructured lipid carriers (NLCs) having both antioxidant and antimicrobial properties produced by α-tocopherol (αT) and levofloxacin (LV), respectively, were developed. The hybrid NLCs were made of solid lipid esters and liquid αT as the central core, plus chitosan (Chi) and poloxamer 188 as surface stabilizers. Three formulations were rationally designed considering lipids with different physicochemical properties: cetyl ester (SS), glyceryl dibehenate (CO) and glyceryl tristearate (DY). The properties and stability of the nanoformulations were studied by dynamic light scattering considering the effects of the homogenization time, surfactant concentration, and initial lipid amount on the mean size, polydispersity index (PDI) and zeta potential of the nanoparticles. The effect of αT on the nanostructuration of the lipid matrix was demonstrated by X-ray diffraction, differential scanning calorimetry, and thermogravimetry analysis. The potential ability of the NLCs to interact with the mucosa was studied by rheological methods, demonstrating a reduction in mucin cohesiveness and elasticity due to the mucoadhesive properties of NLCs coated with chitosan. Solid lipid nanoparticles (SLNs) of SS, CO and DY encapsulated 58.0 ± 3.2, 25.7 ± 7.1, and 27.9 ± 1.5% LV, respectively, while the NLC formulations were able to encapsulate 80–90% LV and allowed controlled release of the drug. The enhanced antimicrobial properties of the SLNs/NLCs against Pseudomonas aeruginosa and Staphylococcus aureus were confirmed. The presence of αT in the formulations provided the antioxidant properties of the NLCs. Finally, no acute toxicities of the formulations were observed in two human lung cell lines (A549 and Calu-3).

PURPOSE OF REVIEW: To review and discuss the findings of systematic reviews that synthesized the evidence on the effect of preoperative exercises (prehabilitation) on postoperative functional recovery in older adults undergoing total knee or hip joint replacement. RECENT FINDINGS: Ten systematic reviews (8 meta-analyses) were included in this review. Findings from the systematic reviews indicated that prehabilitation decreases length of hospital stay but does not improve postoperative functional recovery in older adults undergoing joint replacement. Individual studies in the systematic reviews varied considerably in prehabilitation protocol, assessment timepoints, and outcome measures. Most importantly, systematic reviews did not assess the outcomes pre-post prehabilitation as this timepoint was not addressed in most individual studies. Therefore, it is not known whether the prehabilitation programs improved outcomes preoperatively. SUMMARY: There is a need to develop comprehensive prehabilitation protocols and systematically assess the preoperative and postoperative effectiveness of prehabilitation protocols on functional outcomes (i.e., self-reported and performance-based) in older adults undergoing total joint replacement.

The standard position on moral perfection and gratuitous evil makes the prevention of gratuitous evil a necessary condition on moral perfection. I argue that, on any analysis of gratuitous evil we choose, the standard position on moral perfection and gratuitous evil is false. It is metaphysically impossible to prevent every gratuitously evil state of affairs in every possible world. No matter what God does—no matter how many gratuitously evil states of affairs God prevents—it is necessarily true that God coexists with gratuitous evil in some world or other. Since gratuitous evil cannot be eliminated from metaphysical space, the existence of gratuitous evil presents no objection to essentially omnipotent, essentially omniscient, essentially morally perfect, and necessarily existing beings.

Highly oxygenated organic molecules (HOMs) contribute substantially to the formation and growth of atmospheric aerosol particles, which affect air quality, human health and Earth's climate. HOMs are formed by rapid, gas-phase autoxidation of volatile organic compounds (VOCs) such as α-pinene, the most abundant monoterpene in the atmosphere. Due to their abundance and low volatility, HOMs can play an important role in new-particle formation (NPF) and the early growth of atmospheric aerosols, even without any further assistance of other low-volatility compounds such as sulfuric acid. Both the autoxidation reaction forming HOMs and their NPF rates are expected to be strongly dependent on temperature. However, experimental data on both effects are limited. Dedicated experiments were performed at the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN to address this question. In this study, we show that a decrease in temperature (from +25 to −50 ∘C) results in a reduced HOM yield and reduced oxidation state of the products, whereas the NPF rates (J1.7 nm) increase substantially. Measurements with two different chemical ionization mass spectrometers (using nitrate and protonated water as reagent ion, respectively) provide the molecular composition of the gaseous oxidation products, and a two-dimensional volatility basis set (2D VBS) model provides their volatility distribution. The HOM yield decreases with temperature from 6.2 % at 25 ∘C to 0.7 % at −50 ∘C. However, there is a strong reduction of the saturation vapor pressure of each oxidation state as the temperature is reduced. Overall, the reduction in volatility with temperature leads to an increase in the nucleation rates by up to 3 orders of magnitude at −50 ∘C compared with 25 ∘C. In addition, the enhancement of the nucleation rates by ions decreases with decreasing temperature, since the neutral molecular clusters have increased stability against evaporation. The resulting data quantify how the interplay between the temperature-dependent oxidation pathways and the associated vapor pressures affect biogenic NPF at the molecular level. Our measurements, therefore, improve our understanding of pure biogenic NPF for a wide range of tropospheric temperatures and precursor concentrations.