The influence of the way of regression on the results obtained by the receptorial responsiveness method (RRM), a procedure to estimate a change in the concentration of a pharmacological agonist near the receptor.

The receptorial responsiveness method (RRM) enables the estimation of a change in concentration of an (even degradable) agonist, near its receptor, via curve fitting to (at least) two concentration-effect (E/c) curves of a stable agonist. One curve should be generated before this change, and the other afterwards, in the same system. It follows that RRM yields a surrogate parameter ("cx") as the concentration of the stable agonist being equieffective with the change in concentration of the other agonist. However, regression can be conducted several ways, which can affect the accuracy, precision and ease-of-use. This study utilized data of previous ex vivo investigations. Known concentrations of stable agonists were estimated with RRM by performing individual (local) or global fitting, this latter with one or two model(s), using a logarithmic (logcx) or a nonlogarithmic (cx) parameter (the latter in a complex or in a simplified equation), with ordinary least-squares or robust regression, and with an "all-at-once" or "pairwise" fitting manner. We found that the simplified model containing logcx was superior to all alternative models. The most complicated individual regression was the most accurate, followed closely by the moderately complicated two-model global regression and then by the easy-to-perform one-model global regression. The two-model global fitting was the most precise, followed by the individual fitting (closely) and by the one-model global fitting (from afar). Pairwise fitting (two E/c curves at once) improved the estimation. Thus, the two-model global fitting, performed pairwise, and the individual fitting are recommended for RRM, using the simplified model containing logcx.

An Exploratory Assessment of Factors with Which Influenza Vaccine Uptake Is Associated in Hungarian Adults 65 Years Old and Older: Findings from European Health Interview Surveys.

Influenza vaccination is an imperative public health task for elderly people due to a higher risk of developing more severe complications. The main aim of our study was to determine the influencing factors of being vaccinated against influenza among subjects aged 65 and above. Data were from the Hungarian implementations of the European Health Interview Survey 2009, 2014 and 2019 studies with a final sample size of 3355. A multivariate logistic regression model with interactions was used to identify the possible factors associated with vaccination. Approximately 32% of the participants were vaccinated for the most recent influenza season. The most important factors were identified that contributed to influenza vaccination among individuals, which were the following: educational attainment, having a partner, the annual frequency of specialist and doctor visits, and having comorbidities. Respondents who thought that they could do a lot for their health had higher odds of being immunized. Being obese seemed to be a risk factor. According to our findings, the current influenza vaccination coverage was considered as low in Hungary; hence, the implementation of minor reformulations in the field of health policy is suggested.

The effect of a long-term treatment with cannabidiol-rich hemp extract oil on the adenosinergic system of the zucker diabetic fatty (ZDF) rat atrium.

Cannabidiol (CBD), the most extensively studied non-intoxicating phytocannabinoid, has been attracting a lot of interest worldwide owing to its numerous beneficial effects. The aim of this study was to explore the effect that CBD exerts on the adenosinergic system of paced left atria isolated from obese type Zucker Diabetic Fatty (ZDF) rats, maintained on diabetogenic rat chow, received 60 mg/kg/day CBD or vehicle via gavage for 4 weeks. We found that N6-cyclopentyladenosine (CPA), a relatively stable and poorly transported A1 adenosine receptor agonist, elicited a significantly weaker response in the CBD-treated group than in the vehicle-treated one. In contrast, adenosine, a quickly metabolized and transported adenosine receptor agonist, evoked a significantly stronger response in the CBD-treated group than in the vehicle-treated counterpart (excepting its highest concentrations). These results can be explained only with the adenosine transport inhibitory property of CBD (and not with its adenosine receptor agonist activity). If all the effects of CBD are attributed to the interstitial adenosine accumulation caused by CBD in the myocardium, then a significantly increased adenosinergic activation can be assumed during the long-term oral CBD treatment, suggesting a considerably enhanced adenosinergic protection in the heart. Considering that our results may have been influenced by A1 adenosine receptor downregulation due to the chronic interstitial adenosine accumulation, an adenosinergic activation smaller than it seemed cannot be excluded, but it was above the CBD-naïve level in every case. Additionally, this is the first study offering functional evidence about the adenosine transport inhibitory action of CBD in the myocardium.

Awareness Related to Cardiometabolic Diseases: A Cross-Sectional Study in Southern Vietnam.

BACKGROUND: the prevalence of cardiometabolic diseases (CMDs), such as type 2 diabetes mellitus (T2DM) and hypertension, is increasing rapidly in developing countries. This study aims to assess the awareness of CMD among a selected population in Vietnam. METHOD: a cross-sectional random sample of 402 Vietnamese citizens in two districts (Thu Duc and 12th district) in Ho Chi Minh City were interviewed. Data on knowledge, attitude, and preventive behavior (KAB) of the two conditions were collected through an interview-based questionnaire. RESULTS: the mean (± SD) age was 47.75 (± 15.61) years, and around 60.2% were female. Multiple logistic regression was performed to explore the association of sociodemographic factors, disease status, and awareness of the CMD. Females showed better awareness than males (OR = 3.89 (1.28-11.78)), and those with T2DM and hypertension had a significantly better awareness (OR = 8.33 (2.44-28.37)) than those without CMD. CONCLUSION: the awareness of CMD in our sample was poor. An extensive effort to increase awareness of CMD prevention is needed. Future studies and interventions can be developed more efficiently by targeting the right population.

A Body of Circumstantial Evidence for the Irreversible Ectonucleotidase Inhibitory Action of FSCPX, an Agent Known as a Selective Irreversible A1 Adenosine Receptor Antagonist So Far.

In previous studies using isolated, paced guinea pig left atria, we observed that FSCPX, known as a selective A1 adenosine receptor antagonist, paradoxically increased the direct negative inotropic response to A1 adenosine receptor agonists (determined using concentration/effect (E/c) curves) if NBTI, a nucleoside transport inhibitor, was present. Based on mathematical modeling, we hypothesized that FSCPX blunted the cardiac interstitial adenosine accumulation in response to nucleoside transport blockade, probably by inhibiting CD39 and/or CD73, which are the two main enzymes of the interstitial adenosine production in the heart. The goal of the present study was to test this hypothesis. In vitro CD39 and CD73 inhibitor assays were carried out; furthermore, E/c curves were constructed in isolated, paced rat and guinea pig left atria using adenosine, CHA and CPA (two A1 adenosine receptor agonists), FSCPX, NBTI and NBMPR (two nucleoside transport inhibitors), and PSB-12379 (a CD73 inhibitor), measuring the contractile force. We found that FSCPX did not show any inhibitory effect during the in vitro enzyme assays. However, we successfully reproduced the paradox effect of FSCPX in the rat model, mimicked the "paradox" effect of FSCPX with PSB-12379, and demonstrated the lipophilia of FSCPX, which could explain the negative outcome of inhibitor assays with CD39 and CD73 dissolved in a water-based solution. Taken together, these three pieces of indirect evidence are strong enough to indicate that FSCPX possesses an additional action besides the A1 adenosine receptor antagonism, which action may be the inhibition of an ectonucleotidase. Incidentally, we found that POM-1 inhibited CD73, in addition to CD39.

Predicting the epidemic curve of the coronavirus (SARS-CoV-2) disease (COVID-19) using artificial intelligence: An application on the first and second waves.

OBJECTIVES: The COVID-19 pandemic is considered a major threat to global public health. The aim of our study was to use the official epidemiological data to forecast the epidemic curves (daily new cases) of the COVID-19 using Artificial Intelligence (AI)-based Recurrent Neural Networks (RNNs), then to compare and validate the predicted models with the observed data. METHODS: We used publicly available datasets from the World Health Organization and Johns Hopkins University to create a training dataset, then we employed RNNs with gated recurring units (Long Short-Term Memory - LSTM units) to create two prediction models. Our proposed approach considers an ensemble-based system, which is realized by interconnecting several neural networks. To achieve the appropriate diversity, we froze some network layers that control the way how the model parameters are updated. In addition, we could provide country-specific predictions by transfer learning, and with extra feature injections from governmental constraints, better predictions in the longer term are achieved. We have calculated the Root Mean Squared Logarithmic Error (RMSLE), Root Mean Square Error (RMSE), and Mean Absolute Percentage Error (MAPE) to thoroughly compare our model predictions with the observed data. RESULTS: We reported the predicted curves for France, Germany, Hungary, Italy, Spain, the United Kingdom, and the United States of America. The result of our study underscores that the COVID-19 pandemic is a propagated source epidemic, therefore repeated peaks on the epidemic curve are to be anticipated. Besides, the errors between the predicted and validated data and trends seem to be low. CONCLUSION: Our proposed model has shown satisfactory accuracy in predicting the new cases of COVID-19 in certain contexts. The influence of this pandemic is significant worldwide and has already impacted most life domains. Decision-makers must be aware, that even if strict public health measures are executed and sustained, future peaks of infections are possible. The AI-based models are useful tools for forecasting epidemics as these models can be recalculated according to the newly observed data to get a more precise forecasting.

Vestibular Stimulation May Drive Multisensory Processing: Principles for Targeted Sensorimotor Therapy (TSMT).

At birth, the vestibular system is fully mature, whilst higher order sensory processing is yet to develop in the full-term neonate. The current paper lays out a theoretical framework to account for the role vestibular stimulation may have driving multisensory and sensorimotor integration. Accordingly, vestibular stimulation, by activating the parieto-insular vestibular cortex, and/or the posterior parietal cortex may provide the cortical input for multisensory neurons in the superior colliculus that is needed for multisensory processing. Furthermore, we propose that motor development, by inducing change of reference frames, may shape the receptive field of multisensory neurons. This, by leading to lack of spatial contingency between formally contingent stimuli, may cause degradation of prior motor responses. Additionally, we offer a testable hypothesis explaining the beneficial effect of sensory integration therapies regarding attentional processes. Key concepts of a sensorimotor integration therapy (e.g., targeted sensorimotor therapy (TSMT)) are also put into a neurological context. TSMT utilizes specific tools and instruments. It is administered in 8-weeks long successive treatment regimens, each gradually increasing vestibular and postural stimulation, so sensory-motor integration is facilitated, and muscle strength is increased. Empirically TSMT is indicated for various diseases. Theoretical foundations of this sensorimotor therapy are discussed.

Association between Oral Hygiene and Metabolic Syndrome: A Systematic Review and Meta-Analysis.

Emerging evidence has linked poor oral hygiene to metabolic syndrome (MetS), but previously, no summary of evidence has been conducted on the topic. This systematic review and meta-analysis aims to evaluate the associations of oral hygiene status and care with MetS. A systematic search of the PubMed and Web of Science databases from inception to 17 March 2021, and examination of reference lists was conducted to identify eligible observational studies. A random-effects model was applied to pool the effects of oral hygiene status and care on MetS. Thirteen studies met the inclusion criteria and had sufficient methodological quality. Good oral hygiene status (OR = 0.30 (0.13-0.66); I2 = 91%), frequent tooth brushing (OR = 0.68 (0.58-0.80); I2 = 89%), and frequent interdental cleaning (OR = 0.89 (0.81-0.99); I2 = 27%) were associated with a lower risk of MetS. Only one study examined the association between dental visits and MetS (OR = 1.10 (0.77-1.55)). Our findings suggested that there might be inverse associations of oral hygiene status, tooth-brushing frequency, and interdental cleaning with MetS. However, substantial heterogeneity for tooth-brushing frequency and inconsistent results for oral hygiene status in subgroup analyses were observed. There was insufficient evidence for the association between dental visits and MetS. Further longitudinal studies are needed to investigate these associations.

A Wide Spectrum of Ocular Manifestations Signify Patients with Systemic Sclerosis.

Objectives: Systemic sclerosis (SSc) is a rare, chronic connective tissue disease involving multiple organ systems, including the eye. We evaluated the detailed clinical ocular manifestations of outpatients with SSc.Methods: Demographics, disease duration and subtype, nailfold capillaroscopy (NFC) patterns and laboratory parameters encompassing the autoantibody profile of 51 SSc patients were evaluated, and a general ocular examination was performed for each participant.Results: Twenty-nine patients (56.86%) had eyelid skin alterations, 26 (50.98%) had retinal abnormalities, 26 (50.98%) had cataracts, 8 (15.69%) had conjunctival changes, 7 (13.73%) had iris abnormalities, 33 (64.71%) suffered from dry eye disease (DED), and 11 (21.57%) suffered from glaucoma. Significant positive correlations were found between NFC data and both tear breakup time and Ocular Surface Disease Index test values.Conclusions: Eyelid skin abnormalities, DED and retinal abnormalities are among the most common SSc-related ocular involvements. Diverse ophthalmic findings are attributed to the heterogeneity of SSc.

Assessment of patient flow and optimized use of lean thinking transformation from the perspective of graph theory and spectral graph theory: A case study.

BACKGROUND: Hospital re-engineering initiatives aiming to meet the requirement for patient-centered care often face significant barriers. Opportunities from the optimization of patient flow logistics are often overlooked due to the perception that patient transport related services are ancillary. OBJECTIVES: To reorganize patient pathways by optimizing inpatient assignment and outpatient unit relocation. METHODS: Our analysis was conducted in a campus-based hospital hosting 1694 inpatient beds. Patient flow data was used for algorithm-based optimization to minimize the sum of the distances due to visits to outpatient units and visits by consulting physicians. Inpatients were reordered and outpatient units were relocated to minimize transport need. Optimized schemes were analyzed using graph- and spectral graph theory. RESULTS: Both optimizations yielded an altered hospital layout in which the need for patient transfers decreased (over 30% and 23% in terms of total distance and transfer episodes, respectively). The optimized systems gave rise to buildings with greater specialization, higher importance in terms of contributing to the network architecture, greater synchronization and robustness. CONCLUSIONS: The top-down algorithm-based optimization scheme yielded a system in which the need for cross-building patient transfer decreased. We suggest that network analysis may be a useful tool for capacity planning.

Acute stroke awareness of family physicians: translation of policy to practice.

BACKGROUND: Translating clinical guidelines into routine clinical practice is mandatory to achieve population level improvement of health. Emergence of specific therapy for acute stroke yielded the 'time is brain' concept introducing the need for emergency treatment, pointing to the need for increasing stroke awareness of the general population. General practitioners (GPs) manage chronic diseases and could hence catalyse stroke awareness. In our study, the knowledge of general practitioners toward accurate identification of acute stroke candidacy was investigated. METHODS: GPs and residents in training for family medicine participated in a survey on a voluntary basis using supervised self-administration between the 1st of February 2018 and 31st July 2018. Two clinical cases of acute stroke that differed only regarding the patient's eligibility for intravenous thrombolysis were presented. Participants answered two open-ended questions. Text analysis was performed using NVIVO software. RESULTS: Of the 127 respondents, 69 (54.3%) were female. The median age was 49 (34-62) years. The median time spent working after graduation was 14.5 (2-22.5) years. Board-certified GPs made up 77.2% of the sample. Qualitative analysis revealed stroke as the most frequent diagnosis for both cases. Territorial localization and possible aetiology were also established. Respondents properly identified eligibility for thrombolysis. Quantitative assessment showed that having the practice closer to the stroke centre increases the likelihood of adequate diagnosis for acute stroke. CONCLUSIONS: Our results show that GPs properly diagnose acute stroke and identify intravenous thrombolysis candidates. Moreover, we found that a vigorous acute stroke triage system facilitates the translation of theory into practice.

Socioeconomic Factors Predicting Depression Differ in the Acute Stage and at 1 year After Ischemic Stroke or TIA.

INTRODUCTION: Considerable depressive symptoms follow stroke in about one third of patients. Initial depressive symptoms may wane after the acute phase of stroke, but persisting depressive symptoms adversely affect rehabilitation and quality of life. We set forth to evaluate predictors of depressive symptoms with a focus on socioeconomic factors. METHODS: We evaluated clinical features and socioeconomic characteristics in 233 consecutive patients with acute ischemic stroke or TIA. Depressive symptoms could be evaluated in 168 subjects in the acute phase with a repeated testing after a mean of 14.7 months via telephone interview in 116 patients. Survival status, scores on the Center for Epidemiologic Studies-Depression Scale (CES-D), Beck Depression Inventory (BDI) and disability (modified Rankin scale, mRS) were recorded. RESULTS: In the acute phase, employment status (p = 0.037) and level of education (p = 0.048) whereas one year later dependency (mRS≥3, p = 0.002) and income (p = 0.012) were the significant predictors of the severity of depressive symptoms. A change from independent (mRS≤2) to dependent living predicted worsening depressive symptoms (p = 0.008), whereas improving to functional independence from an initially dependent condition was associated with diminishing depressive symptoms (p = 0.077 for CES-D and p = 0.044 for BDI) in the first year after an acute ischemic cerebrovascular event. CONCLUSIONS: Predictors of the severity of depressive symptoms differed in the acute phase and at follow-up. In addition to disability, education and employment status in the acute phase and income in the late phase predict the severity of depressive symptoms after ischemic stroke or TIA.

Anterior segment parameters associated with extramuscular manifestations in polymyositis and dermatomyositis.

AIM: To evaluate detailed anterior segment parameters of patients with idiopathic inflammatory myopathies (IIM), including polymyositis (PM), and dermatomyositis (DM), and to clarify the associations between these data and clinical variables of IIM. METHODS: Totally 57 PM, 41 DM patients and 62 controls were enrolled in this cross-sectional, observational, case-control study. All study participants underwent Pentacam evaluation. Laboratory investigations consisted of different antibody assays, while extramuscular clinical assessments included Raynaud's phenomenon, dysphagia, interstitial lung disease, arthritis/arthralgia, and weight loss. Objective signs and subjective symptoms of dry eye disease (DED) were also evaluated. RESULTS: All pachymetric parameters [center, apex, thinnest and maximal keratometry (Kmax)] and corneal volume (CV) of both sides of PM patients proved to be significantly lower. Some pachymetric data were also noticed as significantly decreased compared to those of controls. Several significant differences were traced between anterior segment values and extramuscular manifestations of myositis, largely in case of arthritis/arthralgia and weight loss, whereas associations between anterior segment parameters and antibodies were weak. Objective clinical tests of DED were also significantly decreased in IIM patients. CONCLUSION: The results suggest that all IIM patients have thinner corneas compared with those of controls, and decreased corneal parameters are significantly associated with the occurrence of some extramuscular manifestations. In addition, IIM patients tend to develop objective signs of DED.

Negative Inotropic Effect of BGP-15 on the Human Right Atrial Myocardium.

Cardiovascular morbidity and mortality carry great socioeconomic burden worldwide that mandates the development of new, efficacious therapeutic agents with limited adverse effects. O-(3-piperidino-2-hydroxy-1-propyl) nicotinic acid amidoxime (BGP-15) is a known, well-tolerable drug candidate that exerts beneficial effects in several disease models. As BGP-15 has a significant structural similarity with propranolol, it arose that BGP-15 might also have a direct effect on the heart. Thus, in the present work, we investigated the effect of BGP-15 and propranolol on the contractility of isolated, paced, human right atrial samples (obtained from patients undergone open-heart surgery), with or without previous isoproterenol (ISO) stimulation (evoking an indirect or direct effect, respectively). We found that both BGP-15 and propranolol exerted direct as well as indirect negative inotropic effects on the atrial myocardium, reaching similar maximal response. However, BGP-15 had considerably smaller potency than propranolol regarding both types of negative inotropy. In addition, BGP-15, in contrast to propranolol, had a significantly greater indirect negative inotropic effect on samples exhibiting strong response to ISO. Moreover, the indirect negative inotropic effect of BGP-15 was significantly greater on samples derived from diabetic patients than on samples obtained from non-diabetic ones. Our results suggest that the enhanced ISO sensitivity is associated with the diabetic state, and BGP-15 exerts greater negative inotropic effect on the human atrial myocardium in both conditions (as compared to the atrial tissue that is not ISO oversensitive and/or diabetic). Additionally, the negative inotropic effects of BGP-15 and propranolol seem to be mediated by in part different molecular pathways in the atrial myocardium.

Corneal Involvement of Patients with Polymyositis and Dermatomyositis.

Purpose: To evaluate corneal parameters in patients with polymyositis (PM) and dermatomyositis (DM) and compare them with those of healthy controls.Methods: A total of 43 PM and 32 DM patients and 93 controls were enrolled in this cross-sectional, observational, case-control study. Corneal parameters were evaluated by Pentacam. Objective clinical tests of dry eye disease (DED) were also performed.Results: All pachymetric measurements and corneal volumes (CVs) proved to be significantly lower both in PM and DM patients. The values of DM patients were closer to control values than those of the PM patients. For tear break-up time and Schirmer-I test values significant differences were observed between patients and controls, with values decreased both in PM and DM patients.Conclusions: PM patients rather than DM patients tend to develop thinner and low-volume corneas as compared to controls. Additionally, a high prevalence of DED among both PM and DM patients was also detected.

Accuracy and Precision of the Receptorial Responsiveness Method (RRM) in the Quantification of A1 Adenosine Receptor Agonists.

The receptorial responsiveness method (RRM) is a procedure that is based on a simple nonlinear regression while using a model with two variables (X, Y) and (at least) one parameter to be determined (cx). The model of RRM describes the co-action of two agonists that consume the same response capacity (due to the use of the same postreceptorial signaling in a biological system). While using RRM, uniquely, an acute increase in the concentration of an agonist (near the receptors) can be quantified (as cx), via evaluating E/c curves that were constructed with the same or another agonist in the same system. As this measurement is sensitive to the implementation of the curve fitting, the goal of the present study was to test RRM by combining different ways and setting options, namely: individual vs. global fitting, ordinary vs. robust fitting, and three weighting options (no weighting vs. weighting by 1/Y2 vs. weighting by 1/SD2). During the testing, RRM was used to estimate the known concentrations of stable synthetic A1 adenosine receptor agonists in isolated, paced guinea pig left atria. The estimates were then compared to the known agonist concentrations (to assess the accuracy of RRM); furthermore, the 95% confidence limits of the best-fit values were also considered (to evaluate the precision of RRM). It was found that, although the global fitting offered the most convenient way to perform RRM, the best estimates were provided by the individual fitting without any weighting, almost irrespective of the fact whether ordinary or robust fitting was chosen.

Notification Strategy and Predictors of Outcome in Stroke Ineligible for Reperfusion Therapies.

Background, Objective: At least 70% of all stroke patients are ineligible for recanalization therapy. We identified predictors of outcome among these patients, with special focus on notification of emergency medical services (EMS). Methods: We prospectively collected data of 250 consecutive patients with acute cerebrovascular diseases ineligible for recanalization therapy. Initial notification strategy and outcome were analyzed by regression models. Results: EMS notification rate was 55, 41, and 21% in patients with <6, 6-24, and >24 h stroke-to-door time. Atrial fibrillation (AF; OR = 2.66, 95% CI: 1.19-5.96), stroke severity (National Institutes of Health Stroke Scale score, NIHSS; OR = 1.12, 95% CI: 1.02-1.23), history of any psychiatric disease (OR = 2.2, 95% CI: 0.98-4.97), aphasia (OR = 1.99, 95% CI: 0.99-3.98), and residence type were predictors of EMS notification. Disability (modified Rankin Scale score [mRS]) both at discharge and at 1 year was associated with age, admission NIHSS score, type of cerebrovascular disorder, and pre-stroke mRS at discharge and discharge mRS at follow-up. Age (HR = 1.05, 95% CI: 1.02-1.08) and NIHSS (HR = 1.16, 95% CI: 1.12-1.21) had a significant effect on the relative hazard of death. Conclusions: EMS notification is influenced by AF, stroke severity, psychiatric disease, aphasia, and residence type. Early disability depends on age, the type and severity of the stroke, and pre-stroke mRS. Predictors of disability at 1 year after stroke are age, stoke severity, mRS at discharge, and recurrent ischemic stroke. Higher NIHSS and older age are associated with higher case fatality. In patients ineligible for recanalization, EMS notification had no significant effect on outcome, regarding both disability and survival.

Corneal Manifestations of Inflammatory Bowel Disease.

Purpose: To evaluate detailed corneal parameters of inflammatory bowel disease (IBD) patients, including Crohn's disease (CD) and ulcerative colitis (UC) patients, and to assess associations between anterior segment values and other clinical variables.Methods: This prospective cross-sectional case-control study at a tertiary referral center included 30 CD patients, 36 UC patients and 80 age- and gender-matched controls with no ocular symptoms or ocular surface disorders. All study participants underwent a comprehensive ophthalmological evaluation with special interest in dry eye disease (DED). Corneal parameters were evaluated by Pentacam.Results: The mean age of CD patients, UC patients, and controls was 45.80 ± 11.55 years, 52.00 ± 16.05, and 50.68 ± 14.62, respectively. The average disease duration was 12.72 ± 5.83 years for CD patients and 15.94 ± 10.09 years for UC patients. All pachymetric (center, apex and thinnest) and corneal volume (CV) measurements were significantly decreased, while anterior chamber angle width (ACA) values were significantly increased on both sides in all IBD patients compared to those in controls (p < .05). In addition, several anterior segment parameters were altered unilaterally in CD or UC patients. Negative correlations were found between corneal parameters and Schirmer I test values.Conclusions: Our investigations suggest that IBD patients have thinner corneas compared to that of controls. The coexistence of reduced tear quantity seems to have an additional impact on the thinning of the cornea in IBD patients. Early recognition of corneal impairments, a possible extraintestinal manifestation of IBD, should be included in the disease checkup to reduce vision-threatening developments.

An Advanced In Silico Modelling of the Interaction between FSCPX, an Irreversible A1 Adenosine Receptor Antagonist, and NBTI, a Nucleoside Transport Inhibitor, in the Guinea Pig Atrium.

In earlier studies, we generated concentration-response (E/c) curves with CPA (N6-cyclopentyladenosine; a selective A1 adenosine receptor agonist) or adenosine, in the presence or absence of S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine (NBTI, a selective nucleoside transport inhibitor), and with or without a pretreatment with 8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)-benzoyloxy)propyl]-N1-propylxanthine (FSCPX, a chemical known as a selective, irreversible A1 adenosine receptor antagonist), in isolated, paced guinea pig left atria. Meanwhile, we observed a paradoxical phenomenon, i.e. the co-treatment with FSCPX and NBTI appeared to enhance the direct negative inotropic response to adenosine. In the present in silico study, we aimed to reproduce eight of these E/c curves. Four models (and two additional variants of the last model) were constructed, each one representing a set of assumptions, in order to find the model exhibiting the best fit to the ex vivo data, and to gain insight into the paradoxical phenomenon in question. We have obtained in silico evidence for an interference between effects of FSCPX and NBTI upon our ex vivo experimental setting. Regarding the mechanism of this interference, in silico evidence has been gained for the assumption that FSCPX inhibits the effect of NBTI on the level of endogenous (but not exogenous) adenosine. As an explanation, it may be hypothesized that FSCPX inhibits an enzyme participating in the interstitial adenosine formation. In addition, our results suggest that NBTI does not stop the inward adenosine flux in the guinea pig atrium completely.

Altered irisin/BDNF axis parallels excessive daytime sleepiness in obstructive sleep apnea patients.

STUDY OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a sleep-related breathing disorder, characterized by excessive daytime sleepiness (EDS), paralleled by intermittent collapse of the upper airway. EDS may be the symptom of OSAHS per se but may also be due to the alteration of central circadian regulation. Irisin is a putative myokine and has been shown to induce BDNF expression in several sites of the brain. BDNF is a key factor regulating photic entrainment and consequent circadian alignment and adaptation to the environment. Therefore, we hypothesized that EDS accompanying OSAHS is reflected by alteration of irisin/BDNF axis. METHODS: Case history, routine laboratory parameters, serum irisin and BDNF levels, polysomnographic measures and Epworth Sleepiness Scale questionnaire (ESS) were performed in a cohort of OSAHS patients (n = 69). Simple and then multiple linear regression was used to evaluate data. RESULTS: We found that EDS reflected by the ESS is associated with higher serum irisin and BDNF levels; ß: 1.53; CI: 0.35, 6.15; p = 0.012 and ß: 0.014; CI: 0.0.005, 0.023; p = 0.02, respectively. Furthermore, influence of irisin and BDNF was significant even if the model accounted for their interaction (p = 0.006 for the terms serum irisin, serum BDNF and their interaction). Furthermore, a concentration-dependent effect of both serum irisin and BDNF was evidenced with respect to their influence on the ESS. CONCLUSIONS: These results suggest that the irisin-BDNF axis influences subjective daytime sleepiness in OSAS patients reflected by the ESS. These results further imply the possible disruption of the circadian regulation in OSAHS. Future interventional studies are needed to confirm this observation.