Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.

BACKGROUND: Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm. OBJECTIVES: To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism. METHODS: A 6-week randomised, crossover, double-blinded and placebo-controlled feasibility study of usual dose hydrocortisone in PAI administered as either pulsed subcutaneous or standard care in Bristol, United Kingdom (ISRCTN67193733). Participants were stratified by adrenal insufficiency type. All participants who received study drugs are included in the analysis. The primary outcome, the facial expression recognition task (FERT), occurred at week 6. RESULTS: Between December 2014 and 2017, 22 participants were recruited - 20 completed both arms, and 21 were analysed. The pump was well-tolerated. No change was seen in the FERT primary outcome; however, there were subjective improvements in fatigue and mood. Additionally, functional magnetic resonance imaging revealed differential neural processing to emotional cues and visual stimulation. Region of interest analysis identified the left amygdala and insula, key glucocorticoid-sensitive regions involved in emotional ambiguity. FERT post hoc analysis confirmed this response. There were four serious adverse events (AE): three intercurrent illnesses requiring hospitalisation (1/3, 33.3% pump) and a planned procedure (1/1, 100% pump). There was a small number of expected AEs: infusion site bruising/itching (3/5, 60% pump), intercurrent illness requiring extra (3/7, 42% pump) and no extra (4/6, 66% pump) steroid. CONCLUSIONS: These findings support the administration of hormone therapy that mimics physiology.

Assessing Electroencephalography as a Stress Indicator: A VR High-Altitude Scenario Monitored through EEG and ECG.

Over the last decade, virtual reality (VR) has become an increasingly accessible commodity. Head-mounted display (HMD) immersive technologies allow researchers to simulate experimental scenarios that would be unfeasible or risky in real life. An example is extreme heights exposure simulations, which can be utilized in research on stress system mobilization. Until recently, electroencephalography (EEG)-related research was focused on mental stress prompted by social or mathematical challenges, with only a few studies employing HMD VR techniques to induce stress. In this study, we combine a state-of-the-art EEG wearable device and an electrocardiography (ECG) sensor with a VR headset to provoke stress in a high-altitude scenarios while monitoring EEG and ECG biomarkers in real time. A robust pipeline for signal clearing is implemented to preprocess the noise-infiltrated (due to movement) EEG data. Statistical and correlation analysis is employed to explore the relationship between these biomarkers with stress. The participant pool is divided into two groups based on their heart rate increase, where statistically important EEG biomarker differences emerged between them. Finally, the occipital-region band power changes and occipital asymmetry alterations were found to be associated with height-related stress and brain activation in beta and gamma bands, which correlates with the results of the self-reported Perceived Stress Scale questionnaire.

Classification of COPD patients and compliance to recommended treatment in Greece according to GOLD 2017 report: the RELICO study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multifactorial clinical condition, characterized by chronic progressive (or worsening) respiratory symptoms, structural pulmonary abnormalities, and impaired lung function, and is often accompanied by multiple, clinically significant comorbid disorders. In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a new report on COPD prevention, diagnosis and management, aiming at personalizing the maintenance therapeutic approach of the stable disease, based on the patients' symptoms and history of exacerbations (ABCD assessment approach). Our objective was to evaluate the implementation of GOLD suggestions in everyday clinical practice in Greece. METHODS: This was a cross-sectional observational study. Sixty-five different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, vaccination data, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, COPD treatments) were collected from 3615 nation-wide COPD patients (Greece). RESULTS: The mean age at the time of initial COPD diagnosis was 63.8 (± 10.2). Almost 60% of the subjects were classified into group B, while the remaining patients were falling into groups A (18%) and D (21%), and only a small minority of patients belonged to Group C, according to the ABCD assessment approach. The compliance of respiratory physicians to the GOLD 2017 therapeutic suggestions is problematic, especially when it comes to COPD patients belonging to Group A. CONCLUSION: Our data provide valuable information regarding the demographic and medical profile of COPD patients in Greece, the domains which the revised ABCD assessment approach may show some clinical significance on, and the necessity for medical practitioners dealing with COPD patients to adhere closer to international recommendations for the proper management of the disease.

EEG-Based Eye Movement Recognition Using Brain-Computer Interface and Random Forests.

Discrimination of eye movements and visual states is a flourishing field of research and there is an urgent need for non-manual EEG-based wheelchair control and navigation systems. This paper presents a novel system that utilizes a brain-computer interface (BCI) to capture electroencephalographic (EEG) signals from human subjects while eye movement and subsequently classify them into six categories by applying a random forests (RF) classification algorithm. RF is an ensemble learning method that constructs a series of decision trees where each tree gives a class prediction, and the class with the highest number of class predictions becomes the model's prediction. The categories of the proposed random forests brain-computer interface (RF-BCI) are defined according to the position of the subject's eyes: open, closed, left, right, up, and down. The purpose of RF-BCI is to be utilized as an EEG-based control system for driving an electromechanical wheelchair (rehabilitation device). The proposed approach has been tested using a dataset containing 219 records taken from 10 different patients. The BCI implemented the EPOC Flex head cap system, which includes 32 saline felt sensors for capturing the subjects' EEG signals. Each sensor caught four different brain waves (delta, theta, alpha, and beta) per second. Then, these signals were split in 4-second windows resulting in 512 samples per record and the band energy was extracted for each EEG rhythm. The proposed system was compared with naïve Bayes, Bayes Network, k-nearest neighbors (K-NN), multilayer perceptron (MLP), support vector machine (SVM), J48-C4.5 decision tree, and Bagging classification algorithms. The experimental results showed that the RF algorithm outperformed compared to the other approaches and high levels of accuracy (85.39%) for a 6-class classification are obtained. This method exploits high spatial information acquired from the Emotiv EPOC Flex wearable EEG recording device and examines successfully the potential of this device to be used for BCI wheelchair technology.

Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent approaches towards the experimental simulation of congenital and early-age-occurring hypothyroidism.

Carnitine modulates crucial myocardial adenosine triphosphatases and acetylcholinesterase enzyme activities in choline-deprived rats.

Choline is an essential nutrient, and choline deficiency has been associated with cardiovascular morbidity. Choline is also the precursor of acetylcholine (cholinergic component of the heart's autonomic nervous system), whose levels are regulated by acetylcholinesterase (AChE). Cardiac contraction-relaxation cycles depend on ion gradients established by pumps like the adenosine triphosphatases (ATPases) Na(+)/K(+)-ATPase and Mg(2+)-ATPase. This study aimed to investigate the impact of dietary choline deprivation on the activity of rat myocardial AChE (cholinergic marker), Na(+)/K(+)-ATPase, and Mg(2+)-ATPase, and the possible effects of carnitine supplementation (carnitine, structurally relevant to choline, is used as an adjunct in treating cardiac diseases). Adult male albino Wistar rats were distributed among 4 groups, and were fed a standard or choline-deficient diet for one month with or without carnitine in their drinking water (0.15% w/v). The enzyme activities were determined spectrophotometrically in the myocardium homogenate. Choline deficiency seems to affect the activity of the aforementioned parameters, but only the combination of choline deprivation and carnitine supplementation increased myocardial Na(+)/K(+)-ATPase activity along with a concomitant decrease in the activities of Mg(2+)-ATPase and AChE. The results suggest that carnitine, in the setting of choline deficiency, modulates cholinergic myocardial neurotransmission and the ATPase activity in favour of cardiac work efficiency.

Intracerebroventricular administration of streptozotocin as an experimental approach to Alzheimer's disease.

The in vivo experimental simulation of Alzheimer's disease (AD) has been a field of paramount importance for Experimental Medicine and Neuroscience for more than 20 years. We herein provide a short overview of an experimental approach to sporadic AD that is based on the insulin-resistant state induced in the brains of animals following the intracerebroventricular (icv) administration of streptozotocin (STZ) at low doses. The icv administration of STZ is considered as an established, standardized and reproducible approach to sporadic AD, central aspects of the pathology of which it can reliably simulate.

Recent advances in the crosstalk between the brain-derived neurotrophic factor and glucocorticoids.

Brain-derived neurotrophic factor (BDNF), a key neurotrophin within the brain, by selectively activating the TrkB receptor, exerts multimodal effects on neurodevelopment, synaptic plasticity, cellular integrity and neural network dynamics. In parallel, glucocorticoids (GCs), vital steroid hormones, which are secreted by adrenal glands and rapidly diffused across the mammalian body (including the brain), activate two different groups of intracellular receptors, the mineralocorticoid and the glucocorticoid receptors, modulating a wide range of genomic, epigenomic and postgenomic events, also expressed in the neural tissue and implicated in neurodevelopment, synaptic plasticity, cellular homeostasis, cognitive and emotional processing. Recent research evidences indicate that these two major regulatory systems interact at various levels: they share common intracellular downstream pathways, GCs differentially regulate BDNF expression, under certain conditions BDNF antagonises the GC-induced effects on long-term potentiation, neuritic outgrowth and cellular death, while GCs regulate the intraneuronal transportation and the lysosomal degradation of BDNF. Currently, the BDNF-GC crosstalk features have been mainly studied in neurons, although initial findings show that this crosstalk could be equally important for other brain cell types, such as astrocytes. Elucidating the precise neurobiological significance of BDNF-GC interactions in a tempospatial manner, is crucial for understanding the subtleties of brain function and dysfunction, with implications for neurodegenerative and neuroinflammatory diseases, mood disorders and cognitive enhancement strategies.

Sleep disorders and Alzheimer's disease pathophysiology: The role of the Glymphatic System. A scoping review.

BACKGROUND: Alzheimer's disease (AD) is highly intertwined with sleep disturbances throughout its whole natural history. Sleep consists of a major compound of the functionality of the glymphatic system, as the synchronized slow-wave activity during NREM facilitates cerebrospinal and interstitial long-distance mixing. OBJECTIVE: The present study undertakes a scoping review of research on the involvement of the glymphatic system in AD-related sleep disturbances. DESIGN: we searched Medline, Embase, PsychInfo and HEAL-link databases, without limitations on date and language, along with reference lists of relevant reviews and all included studies. We included in vivo, in vitro and post-mortem studies examining glymphatic implications of sleep disturbances in human populations with AD spectrum pathology. A thematic synthesis of evidence based on the extracted content was applied and presented in a narrative way. RESULTS: In total, 70 original research articles were included and were grouped as following: a) Protein aggregation and toxicity, after sleep deprivation, along with its effects on sleep architecture, b) Glymphatic Sequalae in SDB, yielding potential glymphatic markers c) Circadian Dysregulation, d) Possible Interventions. CONCLUSIONS: this review sought to provide insight into the role of sleep disturbances in AD pathogenesis, in the context of the glymphatic disruption.

Acute hemorrhagic leukoencephalitis following the first dose of BNT162b2 vaccine against SARS-CoV-2: A case report.

Acute hemorrhagic leukoencephalitis (AHLE), is a rare inflammatory demyelinating disorder, variant of acute disseminated encephalomyelitis. The diagnosis of AHLE remains challenging due to the rarity of the disease and the lack of a reliable biomarker. We report here a case of a 73-year-old male patient with a progressive, low-grade febrile confusional syndrome 20 days after receiving the first dose of BNT162b2 vaccine against SARS-CoV-2. Evidence indicative of the underlying condition by an extensive panel of imaging (brain magnetic resonance imaging, computed tomography and digital subtraction angiography), laboratory (complete blood count, biochemistry, coagulation, tests for autoimmune or infectious disorders, tumor markers, hormonal levels, cerebrospinal fluid analysis) and electrodiagnostic tests were scarce, and mainly non-specific. Sequential neuroimaging revealed the appearance of extensive T2 lesions (signs of gliosis) along with multiple hemorrhagic lesions at various cortical sites. The patient was treated with corticosteroids, discontinued due to severe adverse effects, and subsequently with sessions of plasmapheresis and monthly intravenous administration of cyclophosphamide. Considering the rapid aggravation of the patient's neurological status, the MRI findings of cortical lesions and the lack of response to any treatment, a biopsy of a frontal lobe lesion was conducted, confirming the presence of confluent, inflammatory-edematous lesions with scattered areas of necrosis and hemorrhage, and ultimately areas of demyelination, thus confirming the diagnosis of AHLE. After more than 5 months of hospitalization the patient was transferred in a primary care facility and remained in a permanent vegetative state until his death, more than 2 years later.

Developmental neurotoxicity of cadmium on enzyme activities of crucial offspring rat brain regions.

Cadmium (Cd) is an environmental contaminant known to exert significant neurotoxic effects on both humans and experimental animals. The aim of this study was to shed more light on the effects of gestational (in utero) and lactational maternal exposure to Cd (50 ppm of Cd as Cd-chloride in the drinking water) on crucial brain enzyme activities in important rat offspring brain regions (frontal cortex, hippocampus, hypothalamus, pons and cerebellum). Our study provides a brain region-specific view of the changes in the activities of three crucial brain enzymes as a result of the developmental neurotoxicity of Cd. Maternal exposure to Cd during both gestation and lactation results into significant changes in the activities of acetylcholinesterase and Na(+),K(+)-ATPase in the frontal cortex and the cerebellum of the offspring rats, as well as in a significant increase in the hippocampal Mg(2+)-ATPase activity. These brain-region-specific findings underline the need for further research in the field of Cd-induced developmental neurotoxicity. Deeper understanding of the mechanisms underlying the neurodevelopmental deficits taking place due to in utero and early age exposure to Cd could shed more light on the causes of its well-established cognitive implications.

Modulation of crucial adenosinetriphosphatase activities due to U-74389G administration in a porcine model of intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) represents a partially-understood cerebrovascular disease of high incidence, morbidity and mortality. We, herein, report the findings of our study concerning the role of two important adenosinetriphosphatases (ATPases) in a porcine model of spontaneous ICH that we have recently developed (by following recent references as well as previously-established models and techniques), with a focus on the first 4 and 24 h following the lesion's induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates that the examined ICH model does not cause a decrease in Na(+),K(+)-ATPase activity (the levels of which are responsible for a very large part of neuronal energy expenditure) in the perihematomal basal ganglia territory, nor a change in the activity of Mg(2+)-ATPase. This is the first report focusing on these crucial ATPases in the experimental setting of ICH and differs from the majority of the findings concerning the behavior of these (crucial for central nervous system cell survival) enzymes under stroke-related ischemic conditions. The administration of U-74389G (an established antioxidant) in this ICH model revealed an injury specific type of behavior, that could be considered as neuroprotective provided that one considers that Na(+),K(+)- and Mg(2+)-ATPase inhibition might in this case diminish the local ATP consumption.

Modelling the COVID-19 pandemic: Focusing on the case of Greece.

The SARS-CoV-2 infection (COVID-19) pandemic created an unprecedented chain of events at a global scale, with European counties initially following individual pathways on the confrontation of the global healthcare crisis, before organizing coordinated public vaccination campaigns, when proper vaccines became available. In the meantime, the viral infection outbreaks were determined by the inability of the immune system to retain a long-lasting protection as well as the appearance of SARS-CoV-2 variants with differential transmissibility and virulence. How do these different parameters regulate the domestic impact of the viral epidemic outbreak? We developed two versions of a mathematical model, an original and a revised one, able to capture multiple factors affecting the epidemic dynamics. We tested the original one on five European countries with different characteristics, and the revised one in one of them, Greece. For the development of the model, we used a modified version of the classical SEIR model, introducing various parameters related to the estimated epidemiology of the pathogen, governmental and societal responses, and the concept of quarantine. We estimated the temporal trajectories of the identified and overall active cases for Cyprus, Germany, Greece, Italy and Sweden, for the first 250 days. Finally, using the revised model, we estimated the temporal trajectories of the identified and overall active cases for Greece, for the duration of the 1230 days (until June 2023). As shown by the model, small initial numbers of exposed individuals are enough to threaten a large percentage of the population. This created an important political dilemma in most countries. Force the virus to extinction with extremely long and restrictive measures or merely delay its spread and aim for herd immunity. Most countries chose the former, which enabled the healthcare systems to absorb the societal pressure, caused by the increased numbers of patients, requiring hospitalization and intensive care.

Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation.

The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in the context of emotional processing. We combine human cell type and transcriptomic atlas data of high spatial resolution with functional magnetic resonance imaging (fMRI) data. We show that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function. We find that two previously identified key components of rapid non-genomic GC signaling - the ANXA1 gene and retrograde endocannabinoid signaling - show most significant differential expression (q = 3.99e-10) and enrichment (fold enrichment = 5.56, q = 9.09e-4). Our results further indicate that specific cell types, including a specific NPY-expressing GABAergic neuronal cell type, and specific G protein signaling cascades underly the cerebral effects of a loss of ultradian cortisol rhythm. Our results provide a biological mechanistic underpinning of our fMRI findings, indicating specific cell types and cascades as a target for manipulation in future experimental studies.

Activation of acetylcholinesterase after U-74389G administration in a porcine model of intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes. Despite high incidence, morbidity and mortality, the precise pathophysiology of spontaneous ICH is not fully understood, while there is little data concerning the mechanisms that follow the primary insult of the hematoma formation. The cholinergic system, apart from its colossal importance as a neurotransmission system, seems to also play an important role in brain injury recovery. It has been recently suggested that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself. We, herein, report the findings of our study concerning the role of acetylcholinesterase (AChE; a crucial membrane-bound enzyme involved in cholinergic neurotransmission) in a porcine model of spontaneous ICH, with a focus on the first 4 and 24 h following the lesion's induction, in combination with a study of the effectiveness of the lazaroid antioxidant U-74389G administration. Our study demonstrates the activation of AChE activity following U-74389G administration. The lazaroid U-74389G seems to be an established neuroprotectant and this is the first report of its supporting role in the enhancement of cholinergic response to the induction of ICH.

Biphasic Response of Astrocytic Brain-Derived Neurotrophic Factor Expression following Corticosterone Stimulation.

Novel research studies indicate multivarious interactions of glucocorticoid hormones (GCs) with the brain-derived neurotrophic factor (BDNF), regulating important aspects of neuronal cell physiology. While there is recent evidence of the chronic effects of GC stimulation on BDNF levels, as well as of the role of BDNF stimulation in the type of genomic effects following activation of GC-sensitive receptors, no data exist concerning the acute effects of GC stimulation on BDNF/TrkB gene expression. To address this question, we conducted a chrono-pharmacological study on rodent glial cells, astrocytes, which express the BDNF receptor, TrkB, following corticosterone administration. mRNA levels of BDNF and TrkB were estimated 1, 6, 12 and 24 h post-treatment. Selective inhibitors for GC-sensitive receptors and TrkB were used to decipher the molecular pathways of the effects observed. Our data support a biphasic response of BDNF expression after corticosterone stimulation. This response is characterized by a rapid TrkB phosphorylation-dependent upregulation of BDNF mRNA within the first hour, followed by a glucocorticoid receptor (GR)-dependent downregulation of BDNF mRNA, evident at 6, 12 and 24 h, with a direct impact on the protein levels of mature BDNF. Finally, a second pulse of corticosterone administration 1 h prior to the 6, 12 or 24 h timepoints normalized BDNF expression for the corresponding timepoint (i.e., mRNA levels became indifferent from baseline). These results present for the first time a biphasic regulation of the neurotrophin system based on glucocorticoid rhythmicity, further indicating complex trophic responses to temporal hormonal mechanisms in the brain microenvironment.

A case of cerebrotendinous xanthomatosis with brain and spinal involvement without tendon xanthomas: Identification of a novel mutation of the CYP27A1 gene.

Cerebrotendinous xanthomatosis (CTX) is a rare inherited disorder of the alternative pathway of bile acid biosynthesis, due to mutation(s) of the gene CYP27A1, leading to sterol 27-hydroxylase deficiency. The latter results in a systematic deposition of cholestanol and cholesterol to the central nervous system and tendons, premature cataract, as well as the manifestation of systematic symptoms, such as chronic diarrhea, osteoporosis, and premature atherosclerosis. Due to its marked clinical heterogeneity, prompt diagnosis of this disorder is challenging. We present a case of a 38-year-old male with gait difficulty, a progressive deterioration in ambulation, several episodes of vertigo and episodic diarrhea. Clinical history revealed neonatal jaundice, juvenile bilateral cataracts, borderline intellectual capacity, hypothyroidism, testicular cancer. Magnetic resonance imaging demonstrated increased T2-weighted signal in internal capsules, midbrain, cerebellum, and spinal cord. Electrodiagnostic study showed mixed polyneuropathy. Genetic analysis revealed a novel, biallelic, most likely pathogenic mutation, in gene CYP2A1 (c.1410_1411del). Plasma sterol profiling confirmed the diagnosis of CTX. Our patient was treated with chenodeoxycholic acid and one year later, he shows a progressive improvement of gait, normalization of plasma sterol biochemistry and electrophysiological parameters. This case highlights the importance of maintaining a high index of suspicion as the key to an early diagnosis of CTX, taking into consideration its clinical variability and, if promptly identified, the good response to treatment.

Self-perceived quality of sleep among COPD patients in Greece: the SLEPICO study.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide accompanied by a substantial social and economic burden for the patient and the society. Poor sleep quality among COPD patients is frequently unnoticed and unaddressed by physicians and patients themselves, although it is a major source of further deterioration of these patients' quality of life. The aim of the present study was to record the quality of sleep in COPD patients among the Greek population and correlate these findings with various features of these patients, using the COPD and Asthma Sleep Impact Scale (CASIS). This was a cross-sectional observational study. Forty different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, CASIS questionnaire results, COPD assessment test, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, inhaled COPD treatment report) were collected from 3454 nation-wide COPD patients (Greece). The study sample consisted of COPD patients, mainly male (73%) with a median age of 69 years and a median BMI of 27.2. More than half of COPD patients (60.6%) suffered from moderate disease severity and 23.8% from severe disease, while less than half (42.1%) suffered from at least one exacerbation of the disease over the last year prior study enrollment. About 14% reported frequent to very frequent issues affecting their sleep quality, between a fourth and a third of them reported occasional night sleep disturbances, and at least half of them reported no or very infrequent problems in their night sleep. Our study indicates that the COPD assessment test (CAT) and the spirometry-based disease severity can predict the poorness in the quality of sleep (F2,3451 = 1397.5, p < 0.001, adj. R2 = 0.45) as assessed by CASIS score, and that the latter also correlates with age (ρ = 0.122, p < 0.001) and disease duration (ρ = 0.104, p < 0.001). On the contrary, there appears to be no correlation between sleep quality and number of exacerbations. Finally, untreated patients with COPD suffer from poorer quality of sleep compared to treated subjects, independently of the use of inhaled corticosteroids (F2,3451 = 21.65, p < 0.001). The results of the SLEPICO study show that increased age, prolonged disease duration, and especially CAT score ≥ 10, and severe COPD stage, might act as important indicators for deterioration in the quality of sleep, with potential consequences in the daily routine of those patients, thus urging potentially for further pharmacological interventions or modifications.

A Real-World Study on the Day and Night-Time Symptoms Among Greek COPD Patients Who Recently Initiated Treatment with Dual Bronchodilation: The DANICO Study.

Purpose: The rationale of this study was to investigate the prevalence of daily and night symptoms and quality of sleep in Greek COPD patients as a means to evaluate their response to treatment with the fixed dose combination of aclidinium/formoterol (administered through the Genuair® device). Patients and Methods: This study was a multicenter, nationwide, non-interventional, observational study in 2105 patients suffering from COPD, who have recently started treatment with aclidinium/formoterol. Patients were attending to two visits, one baseline and a final visit, 3 months later. Different variables have been collected on either the baseline or the final visit or both: demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, COPD assessment test (CAT), COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach proposed by the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD), COPD treatment report, and severity of early-morning, daytime and night-time COPD-related symptoms. Reasons for prescribing aclidinium/formoterol, satisfaction of patients to the treatment, as well as their compliance have also been recorded. Results: After 3 months on aclidinium/formoterol, 50.1% of the patients experienced an improvement in their early-morning symptoms. Furthermore, 49.9% of them experienced an improvement in their daily symptoms, 44.9% improved their night-time symptoms and 43.2% reduced the frequency of overnight sleep disruptions due to COPD symptoms. These favorable outcomes apply mainly to GOLD Groups B-D. Treatment with aclidinium/formoterol improved on average the pre-bronchodilation FEV1% pred by 3.18%, the post-bronchodilation FEV1% pred by 2.78% and reduced CAT score by 5.22 points. Satisfaction with using aclidinium/formoterol across patients was high, as well as compliance to therapy. Conclusion: Aclidinium/formoterol provided significant benefits on the quality of life of COPD patients by reducing the morning, daytime and the night-time symptoms and symptom burden in GOLD Groups B-D, and activity impairment under real-life conditions in all GOLD ABCD groups.

Continuous Non-Invasive Glucose Monitoring via Contact Lenses: Current Approaches and Future Perspectives.

Diabetes mellitus (DM) is a chronic disease that must be carefully managed to prevent serious complications such as cardiovascular disease, retinopathy, nephropathy and neuropathy. Self-monitoring of blood glucose is a crucial tool for managing diabetes and, at present, all relevant procedures are invasive while they only provide periodic measurements. The pain and measurement intermittency associated with invasive techniques resulted in the exploration of painless, continuous, and non-invasive techniques of glucose measurement that would facilitate intensive management. The focus of this review paper is the existing solutions for continuous non-invasive glucose monitoring via contact lenses (CLs) and to carry out a detailed, qualitative, and comparative analysis to inform prospective researchers on viable pathways. Direct glucose monitoring via CLs is contingent on the detection of biomarkers present in the lacrimal fluid. In this review, emphasis is given on two types of sensors: a graphene-AgNW hybrid sensor and an amperometric sensor. Both sensors can detect the presence of glucose in the lacrimal fluid by using the enzyme, glucose oxidase. Additionally, this review covers fabrication procedures for CL biosensors. Ever since Google published the first glucose monitoring embedded system on a CL, CL biosensors have been considered state-of-the-art in the medical device research and development industry. The CL not only has to have a sensory system, it must also have an embedded integrated circuit (IC) for readout and wireless communication. Moreover, to retain mobility and ease of use of the CLs used for continuous glucose monitoring, the power supply to the solid-state IC on such CLs must be wireless. Currently, there are four methods of powering CLs: utilizing solar energy, via a biofuel cell, or by inductive or radiofrequency (RF) power. Although, there are many limitations associated with each method, the limitations common to all, are safety restrictions and CL size limitations. Bearing this in mind, RF power has received most of the attention in reported literature, whereas solar power has received the least attention in the literature. CLs seem a very promising target for cutting edge biotechnological applications of diagnostic, prognostic and therapeutic relevance.