Influence of data filtering on reliability of respiratory impedance and derived parameters in children

Forced oscillation impedance (Zrs) measurements are frequently corrupted by noisy data in children. Our aim was to improve the reliability of respiratory resistance (Rrs) and routine identification of its flow (V') and volume (V) dependence during tidal breathing, according to Rrs = K1 + K2 x /V'/ + K3 x V. Zrs was measured at 12 Hz, using a head generator in 23 children aged 4-13 years undergoing methacholine (Mch) challenge. Rrs, K1, K2, K3, and residual mean square error (RMSD), as well as reproducibility of the parameters, were obtained. Calculations were performed separately in inspiration and expiration on the raw data, and after eliminating values lying outside confidence intervals ranging from 99% (F3SD) to 95% (F2SD) of the mean Zrs. Filtering decreased RMSD and Rrs, F3SD improved reproducibility of Rrs in expiration compared to raw data. F2SD increased K1 and decreased the amplitude of K2 and K3 before and after Mch compared to F3SD. Rrs and K2 were significantly larger and K3 significantly more negative in expiration than in inspiration at all levels of filtering, probably because of the upper airways. F3SD appeared efficient in eliminating aberrant data, while allowing the identification of physiological variations of Rrs.     

Permanent Cardiac Pacing in the Elderly Patient: Is Selection of the Pacing Mode Important?

Most pacemaker recipients are elderly, and advanced age does not constitute a contraindication to the implantation of a permanent pacemaker. However, pacing in the older patient should no longer be regarded simply as a way to prevent Stokes-Adams attacks or life-threatening bradyarrhythmia. A VVI pacemaker for everyone is now inappropriate, especially in active and otherwise healthy older patients. Selection of the optimal devise or pacing mode in older patients requires an understanding of how aging affects the cardiovascular system (left ventricular diastolic dysfunction) and the natural history of disease, especially sick sinus syndrome after pacemaker implantation. Many retrospective and nonrandomized studies focusing mostly on the sick sinus syndrome have indicated that atrial-based pacing improves the quality and duration of life when compared to single lead ventricle pacing. The lower incidence of chronic atrial fibrillation in patients with atrial-based pacemakers compared to VVI devices is of great importance in the elderly, in whom this arrhythmia is associated with greater morbidity and mortality than in younger individuals. The decreased mortality associated with atrial-based pacing compared to single lead ventricular pacing seems to favor patients older than 70 years. There is now a growing realization that implantation of dual chamber pacemakers in the elderly is cost-effective on a long-term basis by avoiding or reducing the complications associated with single lead ventricular pacing, thereby reducing the need for repeated hospitalizations and medical care.     

Distal common bile duct stenosis secondary to benign duodenal ulceration: report of a case

Obstructive jaundice is a very rare complication of peptic ulcer disease. We report a patient who presented with symptoms suggestive of malignant distal common bile duct stenosis. A final diagnosis of benign duodenal ulcer with stricture of the common bile duct was made. A short review of the literature is also presented.     

Report on a novel emerging class of highly potent benzimidazole NPS opioids: Chemical and in vitro functional characterization of isotonitazene

This paper reports on the identification and full chemical characterization of isotonitazene (N,N‐diethyl‐2‐[5‐nitro‐2‐({4‐[(propan‐2‐yl)oxy]phenyl}methyl)‐1H‐benzimidazol‐1‐yl]ethan‐1‐amine), a potent NPS opioid and the first member of the benzimidazole class of compounds to be available on online markets. Interestingly, this compound was sold under the name etonitazene, a structural analog. Identification of isotonitazene was performed by gas chromatography mass spectrometry (GC–MS) and liquid chromatography time‐of‐flight mass spectrometry (LC‐QTOF‐MS), the latter identifying an exact‐mass m/z value of 411.2398. All chromatographic data indicated the presence of a single, highly pure compound. Confirmation of the specific benzimidazole regio‐isomer was performed using ¹H and ¹³C NMR spectroscopy, after which the chemical characterization was finalized by recording Fourier‐transform (FT‐IR) spectra. A live cell‐based reporter assay to assess the in vitro biological activity at the μ‐opioid receptor (MOR) revealed that isotonitazene has a high potency (EC₅₀ of 11.1 nM) and efficacy (E_max 180% of that of hydromorphone), thus confirming that this substance is a strong opioid. Isotonitazene has not been previously detected, either in powder form, or in biological fluids. The high potency and efficacy of isotonitazene, combined with the fact that this compound was being sold undiluted, represents an imminent danger to anyone aiming to use this powder.     

Regulation of intercellular biomolecule transfer–driven tumor angiogenesis and responses to anticancer therapies

Intercellular biomolecule transfer (ICBT) between malignant and benign cells is a major driver of tumor growth, resistance to anticancer therapies, and therapy-triggered metastatic disease. Here we characterized cholesterol 25-hydroxylase (CH25H) as a key genetic suppressor of ICBT between malignant and endothelial cells (ECs) and of ICBT-driven angiopoietin-2–dependent activation of ECs, stimulation of intratumoral angiogenesis, and tumor growth. Human CH25H was downregulated in the ECs from patients with colorectal cancer and the low levels of stromal CH25H were associated with a poor disease outcome. Knockout of endothelial CH25H stimulated angiogenesis and tumor growth in mice. Pharmacologic inhibition of ICBT by reserpine compensated for CH25H loss, elicited angiostatic effects (alone or combined with sunitinib), augmented the therapeutic effect of radio-/chemotherapy, and prevented metastatic disease induced by these regimens. We propose inhibiting ICBT to improve the overall efficacy of anticancer therapies and limit their prometastatic side effects.     

Dissociations between the Processing of Proper and Common Names

Recently, some authors have claimed that a double dissociation between an "anomia for proper names" and a "selective sparing of proper names" has been demonstrated in the cognitive neuropsychology literature (e.g. Cohen & Burke, 1993; Hittmair-Delazer, Denes, Semenza,& Mantovan,1994; Semenza& Zettin, 1989). The aim of the present paper is to evaluate whether this claim is really tenable or not. We point out the need to distinguish carefully between the production and comprehension of language when looking forsuch a dissociation. We argue that a double dissociation between the processing of proper names and common names has not been demonstrated for production. The evidence for a double dissociation between comprehension of proper names and common names is much stronger, but even this claim is limited.     

Brain dysconnectivity relates to disability and cognitive impairment in multiple sclerosis

The pathophysiology of cognitive dysfunction in multiple sclerosis (MS) is still unclear. This magnetoencephalography (MEG) study investigates the impact of MS on brain resting‐state functional connectivity (rsFC) and its relationship to disability and cognitive impairment. We investigated rsFC based on power envelope correlation within and between different frequency bands, in a large cohort of participants consisting of 99 MS patients and 47 healthy subjects. Correlations were investigated between rsFC and outcomes on disability, disease duration and 7 neuropsychological scores within each group, while stringently correcting for multiple comparisons and possible confounding factors. Specific dysconnections correlating with MS‐induced physical disability and disease duration were found within the sensorimotor and language networks, respectively. Global network‐level reductions in within‐ and cross‐network rsFC were observed in the default‐mode network. Healthy subjects and patients significantly differed in their scores on cognitive fatigue and verbal fluency. Healthy subjects and patients showed different correlation patterns between rsFC and cognitive fatigue or verbal fluency, both of which involved a shift in patients from the posterior default‐mode network to the language network. Introducing electrophysiological rsFC in a regression model of verbal fluency and cognitive fatigue in MS patients significantly increased the explained variance compared to a regression limited to structural MRI markers (relative thalamic volume and lesion load). This MEG study demonstrates that MS induces distinct changes in the resting‐state functional brain architecture that relate to disability, disease duration and specific cognitive functioning alterations. It highlights the potential value of electrophysiological intrinsic rsFC for monitoring the cognitive impairment in patients with MS.     

The role of hippocampal theta oscillations in working memory impairment in multiple sclerosis

Working memory (WM) problems are frequently present in people with multiple sclerosis (MS). Even though hippocampal damage has been repeatedly shown to play an important role, the underlying neurophysiological mechanisms remain unclear. This study aimed to investigate the neurophysiological underpinnings of WM impairment in MS using magnetoencephalography (MEG) data from a visual‐verbal 2‐back task. We analysed MEG recordings of 79 MS patients and 38 healthy subjects through event‐related fields and theta (4–8 Hz) and alpha (8–13 Hz) oscillatory processes. Data was source reconstructed and parcellated based on previous findings in the healthy subject sample. MS patients showed a smaller maximum theta power increase in the right hippocampus between 0 and 400 ms than healthy subjects (p = .014). This theta power increase value correlated negatively with reaction time on the task in MS (r = −.32, p = .029). Evidence was provided that this relationship could not be explained by a ‘common cause’ confounding relationship with MS‐related neuronal damage. This study provides the first neurophysiological evidence of the influence of hippocampal dysfunction on WM performance in MS.     

Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study

BackgroundHigh-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA.MethodsA consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0–1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features.Results528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, p = 0.004 and 2.02, p = 0.012 for LAP and RI > 1.1, respectively) with borderline association with LAP-Vol (OR 1.52, p = 0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, p = 0.003 and 1.04, p = 0.002 for LAP-Vol, respectively).ConclusionsOur results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.