Brain oscillatory patterns in mild cognitive impairment due to Alzheimer's and Parkinson's disease: An exploratory high-density EEG study

Objective: We investigated brain cortical activity alterations, using a resting-state 256-channel high-density EEG (hd-EEG), in Alzheimer's (AD) and Parkinson's (PD) disease subjects with mild cognitive impairment (MCI) and correlations between quantitative spectral EEG parameters and the global cognitive status assessed by Montreal Cognitive Assessment (MoCA) score. Methods: Fifteen AD-MCI, eleven PD-MCI and ten age-matched healthy-controls (HC) underwent hd-EEG recordings and neuropsychological assessment. Cerebrospinal fluid biomarker analysis was performed to obtain well-characterized groups. EEG spectral features were extracted and the differences between the three groups, as well as correlations with MoCA, were investigated. Results: The results showed significantly lower alpha2 power and alpha2/alpha1 ratio in both AD-MCI and PD-MCI compared to controls. The significantly higher theta and lower beta power and alpha/theta ratio were observed in PD-MCI compared to AD-MCI and HC. MoCA score correlated inversely with theta power and directly with alpha2 and beta powers, as well as with alpha2/alpha1 and alpha/theta ratios. Conclusions: This study highlighted significant differences in EEG patterns in AD-MCI and PD-MCI patients and remarked the role of EEG parameters as possible surrogate markers of cognitive status in both neurodegenerative diseases. Significance: In addition to well-established biomarkers, our findings could support early detection of cognitive dysfunction in neurodegenerative disorders and could help to monitor disease progression and therapeutic responses

e-Health solution for home patient telemonitoring in early post-acute TIA/Minor stroke during COVID-19 pandemic

Background: When it comes to critical early post-acute TIA/stroke phase, there is a lack of a comprehensive multi-parametric telemonitoring system. The COVID-19 emergency, its related global mobility restrictions and fear of hospitalization further highlighted the need of a comprehensive solution. Objective: We aimed to design and test a pragmatic e-Health system based on multiparametric telemonitoring to support of TIA/stroke patients in sub-acute phase during the COVID-19 pandemic. Methods: We proposed a telemonitoring system and protocol for TIA/minor stroke patients during COVID-19 pandemic for patients at risk of stroke recurrence. This system involves the use of portable devices for BP/HR/SpO2/temperature sensing, panic-button, gateway, and a dedicated ICT platform. The protocol is a 14-day multiparametric telemonitoring, therapy, and emergency intervention based on vital sign alteration notifications. We conducted a proof-of-concept validation test on 8 TIA/minor stroke patients in the early post-acute phase (< 14 days from ischemic event). Results: The proposed solution allowed to promptly and remotely identify vital sign alterations at home during the early post-acute phase, allowing therapy and behavioral intervention adjustments. Also, we observed a significant improvement of quality of life, as well as a significant reduction of anxiety and depression status. TUQ showed ease of use, good interface quality and high user satisfaction of the proposed solution. The 3-month follow-up showed total adherence of prescribed therapy and no stroke/TIA recurrence or other emergency department admissions. Conclusion: The proposed e-Health solution and telemonitoring protocol may be highly useful for early post-acute remote patient management, thus supporting constant monitoring and patient adherence to the treatment pathway, especially during the COVID-19 emergency

Stability in community-acquired pneumonia: one step forward with markers?

Background: Biological markers as an expression of systemic inflammation have been recognised as useful for evaluating the host response in community-acquired pneumonia (CAP). The objective of this study was to evaluate whether the biological markers procalcitonin (PCT) and C-reactive protein (CRP) might reflect stability after 72 h of treatment and the absence of subsequent severe complications. Methods: A prospective cohort study was performed in 394 hospitalised patients with CAP. Clinical stability was evaluated using modified Halm's criteria: temperature (37.2uC; heart rate (100 beats/min; respiratory rate (24 breaths/min; systolic blood pressure >90 mm Hg; oxygen saturation >90%; or arterial oxygen tension >60 mm Hg. PCT and CRP levels were measured on day 1 and after 72 h. Severe complications were defined as mechanical ventilation, shock and/or intensive care unit (ICU) admission, or death after 72 h of treatment. Results: 220 patients achieved clinical stability at 72 h and had significantly lower levels of CRP (4.2 vs 7 mg/dl) and of PCT (0.33 vs 0.48 ng/ml). Regression logistic analyses were performed to calculate several areas under the ROC curve (AUC) to predict severe complications. The AUC for clinical stability was 0.77, 0.84 when CRP was added (p=0.059) and 0.77 when PCT was added (p=0.45). When clinical stability was achieved within 72 h and marker levels were below the cut-off points (0.25 ng/ml for PCT and 3 mg/dl for CRP), no severe complications occurred. Conclusions: Low levels of CRP and PCT at 72 h in addition to clinical criteria might improve the prediction of absence of severe complications

CFTR regulates B cell activation and lymphoid follicle development

The number of LFs, BAFF+, TLR4+ and proliferation marker Ki67+ B cells in lung explants or resections from subjects with CF and normal controls was quantified by immunostaining. The role of CFTR in B cell activation and LF development was then examined in two independent cohorts of uninfected CFTR-deficient mice (Cftr -/-) and wild type controls. The number of lung LFs, B cells and BAFF+, CXCR4+, immunoglobulin G+ B cells was examined by immunostaining. Lung and splenocyte B cell activation marker and major histocompatibility complex class II (MHC class II) expression was quantified by flow cytometry. Inflammatory cytokine levels were measured in supernatants from isolated B cells from Cftr -/- and wild type mice stimulated in vitro with Pseudomonas aeruginosa lipopolysaccharide (LPS).CT/MA Cystic Fibrosis/Multiple Sclerosis Fund; May Family Trust; CF Foundation [DRUMMR0, DRUMMR1]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Axonal Odorant Receptors Mediate Axon Targeting

In mammals, odorant receptors not only detect odors but also define the target in the olfactory bulb, where sensory neurons project to give rise to the sensory map. The odorant receptor is expressed at the cilia, where it binds odorants, and at the axon terminal. The mechanism of activation and function of the odorant receptor at the axon terminal is, however, still unknown. Here, we identify phosphatidylethanolamine- binding protein 1 as a putative ligand that activates the odorant receptor at the axon terminal and affects the turning behavior of sensory axons.Genetic ablation of phosphatidylethanolamine-binding protein 1 in mice results in a strongly disturbed olfactory sensory map. Our data suggest that the odorant receptor at the axon terminal of olfactory neurons acts as an axon guidance cue that responds to molecules originating in the olfactory bulb. The dual function of the odorant receptor links specificity of odor perception and axon targeting

Acute exacerbations of COPD : risk factors for failure and relapse

Acute exacerbations are a leading cause of worsening COPD in terms of lung function decline, quality of life, and survival. They also have a relevant economic burden on the health care system. Determining the risk factors for acute exacerbation and early relapse could be a crucial element for a better management of COPD patients. This review analyzes the current knowledge and underlines the main risk factors for recurrent acute exacerbations. Comprehensive evaluation of COPD patients during stable phase and exacerbation could contribute to prevent treatment failure and relapses

Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study

This phase II, randomised, double-blind, multicentre study (NCT00930982) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis. Adults who were culture positive for pre-defined potential respiratory pathogens (including Pseudomonas aeruginosa and Haemophilus influenzae) were randomised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days (with 56 days of follow-up). Bacterial density in sputum (primary end-point), pulmonary function tests, health-related quality of life and safety were monitored throughout the study. 60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo. Subjects on ciprofloxacin DPI had a significant reduction (p<0.001) in total sputum bacterial load at the end of treatment (-3.62 log10 CFU·g(-1) (range -9.78-5.02 log10 CFU·g(-1))) compared with placebo (-0.27 log10 CFU·g(-1) (range -7.96-5.25 log10 CFU·g(-1))); the counts increased thereafter. In the ciprofloxacin DPI group, 14 (35%) out of 40 subjects reported pathogen eradication at end of treatment versus four (8%) out of 49 in the placebo group (p=0.001). No abnormal safety results were reported and rates of bronchospasm were low. Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis.Robert Wilson, Tobias Welte, Eva Polverino, Anthony De Soyza, Hugh Greville, Anne O, Donnelle, Jeff Alder, Peter Reimnitz, and Barbara Hampe

B cell–adaptive immune profile in emphysema-predominant chronic obstructive pulmonary disease

Cigarette smoke, the major risk factor for COPD in developed countries, causes pulmonary inflammation that persists long after smoking cessation, suggesting self-perpetuating adaptive immune responses similar to those that occur in autoimmune diseases. Increases in the number and size of B cell–rich lymphoid follicles (LFs) have been shown in patients in severe stages of COPD (4), and increased B-cell products (autoantibodies) have been observed in the blood and lungs of patients with COPD (5, 6). Oligoclonal rearrangement of the immunoglobulin genes has been observed in B cells isolated from COPD LFs, suggesting that a specific antigenic stimulation drives B-cell proliferation. Consistently, we have shown that in the COPD lung, there is an overexpression of BAFF (B-cell activation factor of the TNF family), which is a key regulator of B-cell homeostasis in several autoimmune diseases (7) and is involved in the growth of LFs in COPD. However, a network analysis of lung transcriptomics showed that a prominent B-cell molecular signature characterized emphysema preferentially but was absent in AD independently of the degree of airflow limitation (8). In the current study, we investigated the correlation between B-cell responses in lung tissue from patients with COPD and healthy smokers, and the extent of emphysema versus airflow limitation