Carbenoxolone mitigates extensive fibrosis formation in PLP-induced EAE model and multiple sclerosis serum-exposed pericyte culture.

Introduction: Multiple sclerosis (MS) is one of the most common causes of disability in young adults. Nearly, 85% of MS cases start with attacks and remissions, classified as relapsing-remitting multiple sclerosis (RRMS). With repeating attacks, MS causes brain-spinal cord atrophy and enhanced disability as disease progresses. PLP-induced EAE is one of the most established models for pathophysiology and treatment of RRMS. Recent studies demonstrated the possible role of pericytes in perivascular and intra-lesional fibrosis in PLP-induced EAE, whose importance remains elusive. Hence, we have investigated the possible role of pericytes in fibrosis formation and amelioration with a hemichannel blocker, Carbenoxolone (CBX). Methods: PLP-induced experimental autoimmune encephalitis (EAE) model is used and the effect of CBX is investigated. Clinical scores were recorded and followed. Perivascular Collagen 1 and 3 accumulations were demonstrated as markers of fibrosis in the spinal cord. To delineate the role of pericytes, human brain vascular pericytes (HBVP) were incubated with the sera of MS patients to induce in-vitro MS model and the fibrosis formation was investigated. Results: In the PLP induced in-vivo model, both intracerebroventricular and intraperitoneal CBX have significantly mitigated the disease progression followed by clinical scores, demyelination, and fibrosis. Moreover, CBX significantly mitigated MS-serum-induced fibrosis in the HBVP cell culture. Discussion: The study demonstrated two important findings. First, CBX decreases fibrosis formation in both in-vivo and in-vitro MS models. Secondly, it improves neurological scores and decreases demyelination in the EAE model. Therefore, CBX can be potential novel therapeutic option in treating Multiple Sclerosis.

Clinical predictors of Alzheimer's disease-like brain atrophy in individuals with memory complaints.

OBJECTIVES: The definition and assessment methods for subjective cognitive decline (SCD) vary among studies. We aimed to investigate which features or assessment methods of SCD best predict Alzheimer's disease (AD)-related structural atrophy patterns. METHODS: We assessed 104 individuals aged 55+ with memory complaints but normal cognitive screening. Our research questions were as follows: To improve the prediction of AD related morphological changes, (1) Would the use of a standardized cognitive screening scale be beneficial? (2) Is conducting a thorough neuropsychological evaluation necessary instead of relying solely on cognitive screening tests? (3) Should we apply SCD-plus research criteria, and if so, which criterion would be the most effective? (4) Is it necessary to consider medical and psychiatric comorbidities, vitamin deficiencies, vascular burden on MRI, and family history? We utilized Freesurfer to analyze cortical thickness and regional brain volume meta-scores linked to AD or predicting its development. We employed multiple linear regression models for each variable, with morphology as the dependent variable. RESULTS: AD-like morphology was associated with subjective complaints in males, individuals with advanced age, and higher education. Later age of onset for complaints, complaints specifically related to memory, excessive deep white matter vascular lesions, and using medications that have negative implications for cognitive health (according to the Beers criteria) were predictive of AD-related morphology. The subjective cognitive memory questionnaire scores were found to be a better predictor of reduced volumes than a single-question assessment. It is important to note that not all SCD-plus criteria were evaluated in this study, particularly the APOE genotype, amyloid, and tau status, due to resource limitations. CONCLUSIONS: The detection of AD-related structural changes is impacted by demographics and assessment methods. Standardizing SCD assessment methods can enhance predictive accuracy.

Evaluation of 601 children with multisystem inflammatory syndrome (Turk MISC study).

PURPOSE: Due to its link with the 2019 coronavirus, the multisystem inflammatory syndrome in children (MISC) has garnered considerable international interest. The aim of this study, in which MISC patients were evaluated multicenter, and the data of the third period of the Turk-MISC study group, to compare the clinical and laboratory characteristics and outcomes of MISC patients who did and did not require admission to an intensive care unit (ICU). METHODS: This retrospective multicenter observational study was carried out between June 11, 2021, and January 01, 2022. The demographics, complaints, laboratory results, system involvements, and outcomes of the patients were documented. RESULTS: A total of 601 patients were enrolled; 157 patients (26.1%) required hospitalization in the intensive care unit (ICU). Median age was 8 years (interquartile range (IQR) 4.5-11.3 years. The proportion of Kawasaki disease-like features in the ICU group was significantly higher than in the non-ICU group (56.1% vs. 43.2% p = 0.006). The ICU group had considerably lower counts of both lymphocytes and platelets (lymphocyte count 900 vs. 1280 cells × µL, platelet count 153 vs. 212 cells × 103/ µL, all for p< 0.001). C-reactive protein, procalcitonin, and ferritin levels were significantly higher in the ICU group (CRP 164 vs. 129 mg/L, procalcitonin 9.2 vs. 2.2 µg/L, ferritin 644 vs. 334 µg/L, all for p< 0.001). Being between ages 5-12 and older than 12 increased the likelihood of hospitalization in the ICU by four [95% confidence intervals (CI)1.971-8.627] and six times (95% CI 2.575-14.654), respectively, compared to being between the ages 0-5. A one-unit increase in log D-dimer (µg/L) and log troponin (ng/L) was also demonstrated to increase the need for intensive care by 1.8 (95% CI 1.079-3.233) and 1.4 times (95% CI 1.133-1.789), respectively.     Conclusion: By comparing this study to our other studies, we found that the median age of MISC patients has been rising. Patients requiring an ICU stay had considerably higher levels of procalcitonin, CRP, and ferritin but significantly lower levels of lymphocyte and thrombocyte. In particular, high levels of procalcitonin in the serum might serve as a valuable laboratory marker for anticipating the need for intensive care. WHAT IS KNOWN: • Lymphopenia and thrombocytopenia were an independent predictor factors in patients with MISC who needed to stay in intensive care unit. • The possibility of the need to stay in the intensive care unit in patients with MISC who had Kawasaki disease-like findings was controversial compared with those who did not. WHAT IS NEW: • A one-unit increase log D dimer and log troponin was demonstrated to require for intensive care unit by 1.8 and 1.4 times, respectively. • Serum procalcitonin levels had the best performance to predict stay in the intensive care unit stay.

Effect of different garments on thermophysiological and psychological comfort properties of athletes in a wear trial test.

This paper reports on an experimental investigation of thermophysiological and psychological responses during and after an incremental low- to high-intensity exercise at 27 °C and 45% humidity. Five t-shirt garments were produced from different yarn types, their weights and yarn counts were close to each other. During the wear trials, heat and humidity sensors were placed at four body locations (the chest, back, abdomen, and waist). In addition, dynamic comfort measurements of the upper body were examined using a datalogger and subjective rating scales. This study aimed to investigate the effects of garment type on aerobic performance, microclimate temperature and humidity values, and psychological comfort. It was observed that the relative humidity and temperature of the microclimate were low in fabrics with high air permeability and low thermal resistance values of the Tencel single jersey and polyester mesh knitted fabrics. There was a significant difference in microclimate temperature results of TS coded Tencel single jersey t-shirt sample and other t-shirt samples according to statistical analysis results. On the other hand, the statistical results of the PM coded fabric sample measured at lower humidity in the three body regions were found to be a significantly different from those of the other samples (except TS). Although not statistically significant, the VO2 values and heart rates of these fabrics were lower than those of other fabrics. It was concluded that garments made from Tencel single jersey (TS) and polyester mesh (PM) fabrics affected the performance of athletes positively. Athletes were less forced during the training, and the activity could be maintained more than the others when wearing these clothes.

The effect of ketamine on affective modulation of the startle reflex and its resting-state brain correlates.

Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity is yet to be elucidated. The affect-modulated startle reflex paradigm (AMSR) allows examining the valence-specific aspects of behavioral affective reactivity. We hypothesized that ketamine alters the modulation of the startle reflex during processing of unpleasant and pleasant stimuli and weakens the resting-state functional connectivity (rsFC) within the modulatory pathway, namely between the centromedial nucleus of the amygdala and nucleus reticularis pontis caudalis. In a randomized, double-blind, placebo-controlled, cross-over study, thirty-two healthy male participants underwent ultra-high field resting-state functional magnetic resonance imaging at 7 T before and 24 h after placebo and S-ketamine infusions. Participants completed the AMSR task at baseline and one day after each infusion. In contrast to our hypothesis, ketamine infusion did not impact startle potentiation during processing of unpleasant stimuli but resulted in diminished startle attenuation during processing of pleasant stimuli. This diminishment significantly correlated with end-of-infusion plasma levels of ketamine and norketamine. Furthermore, ketamine induced a decrease in rsFC within the modulatory startle reflex pathway. The results of this first study on the effect of ketamine on the AMSR suggest that ketamine might attenuate the motivational significance of pleasant stimuli in healthy participants one day after infusion.

Evaluation of bisphenol release of different clear aligner materials using the liquid chromatography-mass spectrometry/mass spectrometry method.

OBJECTIVES: To evaluate the bisphenol release of different brands of clear aligner materials. MATERIALS AND METHODS: Six different clear aligner materials were used in this study: Duran (Scheu-Dental GmbH, Iserlohn, Germany), Zendura Flx (Bay Materials LLC, Fremont, CA, USA), Zendura A (Bay Materials), Essix (Raintree Essix Inc., Metairie, LA, USA), Taglus Premium (Laxmi Dental Export Pvt. Ltd, Mumbai, India), and Smart Track (Align Technology, San Jose, CA, USA). The samples were kept in saline solution for 8 weeks in airtight test tubes at 37°C. The ratio between the weights of the samples and the volumes of the dilutions was prepared as 0.1 g/mL as suggested by International Standards Organization parameters. To evaluate the bisphenol release of materials, liquid chromatography-mass spectrometry/mass spectrometry analysis was performed. Data were analyzed with the Kruskal-Wallis test (α = 0.05). RESULTS: Bisphenol A (BPA) values in Smart Track were found to be significantly higher than the Zendura A and Zendura Flx groups (P = .02, P = .03, respectively). There was no statistically significant difference among the samples in terms of Bisphenol F (BPF) values (P = .108). In terms of Bisphenol S (BPS) values, a statistically significant difference was found (P = .002) indicating that Smart Track released significantly more BPS than Zendura A (P = .001). CONCLUSIONS: Under the test conditions, the amounts of leached BPA, BPF, and BPS were less than the reference dose for daily intake. However, the cumulative effect of these appliances should not be underestimated.

Treatment of COVID-19 Vaccine Resistant Migraine Attack with CGRP Monoclonal Antibody: A Case Report.

Many researches have shown that coronavirus infection can lead to neurological symptoms. The most common symptom is headache. Calcitonin gene-related peptide (CGRP), which has an important role in the pathophysiology of migraine, may have an active role in persistent headaches after COVID, due to the structural similarity between the CGRP receptor and the SARS-CoV-2 spike protein. In this case report, the effect of the anti-CGRP monoclonal antibody on the migraine attack occurring after COVID-19 m-RNA vaccine will be discussed. A 55-year-old female patient who is followed up with a diagnosis of chronic migraine, had severe and throbbing headache that started after the COVID-19 m-RNA vaccine. After galcanezumab (CGRP monoclonal antibody - CGRP mAb) was started in the patient whose complaints did not regress despite the adjustment of the current drug doses, clinically significant improvement was observed in her complaints after the first dose and it was planned to continue with 120 mg CGRP mAb per month in her follow-ups.

Individual-based predominance of visual input in multisensorial integration for balance is correlated with proprioceptive drift in rubber hand illusion.

Rubber hand illusion (RHI) is a traditional task that examines multisensory integration. The visual capture of tactile stimulus given to the seen rubber hand was considered to predominate the sensory processing and interfere with the bottom-up proprioceptive and tactile inputs received from the unseen real hand that results in mislocalization of participants hand towards rubber hand, namely proprioceptive drift (PD). Another task that requires multisensorial integration and shows a predominance of visual input is the maintenance of body posture. However, if the predominance of visual input in one task is generalizable to another task is yet to be elucidated. We aimed to examine if individual dependency on visual inputs in multisensorial integration in balance correlated with PD in RHI. Twenty healthy participants were recruited for the study and completed the RHI task. The contribution of visual inputs to the static body balance was measured with the instrumented clinical test of sensory interaction for balance and indexed with Romberg Quotient (RQ). We found a moderate positive correlation between PD and RQ. Individuals with more dependence on visual information in maintaining body posture had higher PD in RHI. Our results indicate that there can be an individual-based dependence on particular domains of sensory input preserved during different tasks of multisensorial integration. Future studies must clarify whether this tendency relates to certain physical or physiological traits.

Protective Effects of Infliximab Against Kanamycin-Induced Ototoxicity in Rats.

HYPOTHESIS: To examine the protective effects of infliximab (INF) against kanamycin (KM)-induced hearing loss. BACKGROUND: Tumor necrosis factor α blockers can reduce cellular inflammatory reactions and decrease cell death. METHODS: Thirty-six rats with normal hearing were randomly divided into six groups. The first group was injected with 400 mg/kg KM intramuscularly (IM), the second group with 7 mg/kg INF intraperitoneally (IP) and 400 mg/kg KM IM, the third group with 7 mg/kg INF IP and 200 mg/kg KM IM, and the fourth group with 1 mg/kg 6-methylprednisolone (MP) IP and 400 mg/kg KM IM. Group 5 was injected with 1 mg/kg MP IP and 200 mg/kg KM IM, and group 6 with saline IP once. Auditory brain-stem response (ABR) for hearing thresholds was performed on days 7 and 14. From the frozen sections of the cochlea, the area of the stria vascularis, the number of neurons in the spiral ganglion, the fluorescence intensity of hair cells (FIHC), postsynaptic density (PSD), and presynaptic ribbons (PSRs) were calculated. RESULTS: The KM-induced increase in hearing thresholds was detected on the 14th day. Hearing was only preserved in the group treated with INF after low-dose KM exposure but not in the groups that received high-dose KM. The FIHC, excitatory PSD, and PSR were preserved only in the INF-treated group after half-dose KM exposure. In MP groups, FIHC, excitatory PSD, and PSR were significantly lower than in the control group. CONCLUSIONS: Our results support that tumor necrosis factor-based inflammation may play a role in the ototoxicity mechanism.

Current Smoking Determines the Levels of Circulating MPO and MMP-9 in Adults with Coronary Artery Disease and Obstructive Sleep Apnea.

(1) Background: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which a rupture of atherosclerotic plaques and oxidative stress play a role in the initiation and progression of the disorder. Circulating levels of myeloperoxidase (MPO), as an oxidative stress marker, as well as matrix metalloproteinase-9 (MMP-9), as a destabilizer of plaques, are known to be elevated in patients with CAD and are associated with worse prognosis. Some studies have suggested that OSA is associated with MPO and MMP-9, but the effect of OSA on these biomarkers in cardiac cohorts is unknown. (2) Aims: We addressed the determinants of high MPO and MMP-9 in a CAD cohort with concomitant OSA. (3) Materials and Methods: The current study was a secondary analysis of the RICCADSA trial that was conducted in Sweden between 2005 and 2013. A total of 502 revascularized CAD patients with OSA (apnea-hypopnea index [AHI] ≥ 15 events/h; n = 391) or no-OSA (AHI < 5 events/h; n = 101), based on a home sleep apnea test, and who had blood samples at baseline were included in the analysis. The patients were dichotomized into a high or low MPO and MMP-9 groups, based on the median cut-off values. (4) Results: The mean age of the participants was 63.9 (±8.6), and 84% of the study cohort were men. Median values of MPO and MMP-9 levels were 116 ng/mL and 269 ng/mL, respectively. In different multivariate linear and logistic regression models, neither OSA nor OSA severity in terms of AHI and oxygenation indices were associated with the high MPO and MMP-9 levels. Current smoking was significantly associated with both high MPO (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.06-2.84; p = 0.030) and high MMP-9 levels (OR 2.41, 95% CI 1.44-4.03; p < 0.001), respectively. Other significant determinants were revealed as beta blocker use (OR 1.81, 95% CI 1.04-3.16; p = 0.036) for high MPO as well as male sex (OR 2.07, 95% CI 1.23-3.50; p = 0.006) and calcium antagonist use (OR 1.91, 95% CI 1.18-3.09; p = 0.008) for high MMP-9 levels. (5) Conclusions: Current smoking, but not OSA, was significantly associated with high MPO and MMP-9 levels in this revascularized CAD cohort. Smoking status should be seriously taken into consideration while evaluating the effects of OSA and its treatment on long-term adverse cardiovascular outcomes in adults with CAD.

Towards a better understanding of commonly used medicinal plants from Turkiye: Detailed phytochemical screening and biological activity studies of two Teucrium L. species with in vitro and in silico approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, Teucrium L. species have been among the most commonly used traditional medicinal plants mainly in the Mediterranean region. From tackling gastrointestinal problems to maintaining the healthy functioning of endocrine glands, and from treating malaria to severe dermatological disorders, Teucrium species are known to have extensive therapeutic applications. Teucrium polium L. and Teucrium parviflorum Schreb. are the two members of the genus that have been used in Turkish folk medicine for various medicinal purposes. AIM OF THE STUDY: To determine the phytochemical compositions of the essential oils and ethanol extracts of Teucrium polium and Teucrium parviflorum collected from different locations in Turkiye along with the investigation of in vitro antioxidant, anticancer, antimicrobial activities, and both in vitro and in silico enzyme inhibitory activities of the extracts. MATERIALS AND METHODS: Ethanol extracts of Teucrium polium aerial parts and roots, and aerial parts of Teucrium parviflorum were prepared. Volatile profiling of the essential oils by GC-MS, phytochemical profiling of the ethanol extracts by LC-HRMS, antioxidant activity by DPPH radical scavenging, ABTS cation radical scavenging, CUPRAC, and metal chelating activity assays, anticholinesterase, antityrosinase, antiurease, activities by different enzyme inhibitory activity assays, anticancer activity by SRB cell viability assay, and antimicrobial activity against a standard panel of bacteria and fungi by the microbroth dilution technique. Molecular docking studies were performed by Autodock Vina (Ver. 1.1.2). RESULTS: The studied extracts were found to be quite rich in various biologically important volatile and phenolic compounds. (-)-Epigallocatechin gallate, which is a molecule renowned for having great therapeutic potential, was the major compound of all extracts. Teucrium polium aerial parts extract was revealed as a great source for naringenin with 16327 ± 685.23 µg/g extract. All extracts exerted significant antioxidant activity by different methods. All extracts demonstrated antibutrylcholinesterase, antityrosinase, and antiurease activities by in vitro and in silico assays. Teucrium polium roots extract stood out with remarkable tyrosinase and urease inhibitory and cytotoxic activities. CONCLUSION: The obtained results from this multi-disciplinary study proves that the traditional use of these two Teucrium species is justified, and the mechanisms behind are enlightened.

Hyperglycemia with or without insulin resistance triggers different structural changes in brain microcirculation and perivascular matrix.

Both type-1 and type-2 DM are related to an increased risk of cognitive impairment, neurovascular complications, and dementia. The primary triggers for complications are hyperglycemia and concomitant insulin resistance in type-2 DM. However, the diverse mechanisms in the pathogenesis of diabetes-related neurovascular complications and extracellular matrix (ECM) remodeling in type-1 and 2 have not been elucidated yet. Here, we investigated the high fat-high sucrose (HFHS) feeding model and streptozotocin-induced type-1 DM model to study the early effects of hyperglycemia with or without insulin resistance to demonstrate the brain microcirculatory changes, perivascular ECM alterations in histological sections and 3D-reconstructed cleared brain tissues. One of the main findings of this study was robust rarefaction in brain microvessels in both models. Interestingly, the HFHS model leads to widespread non-functional angiogenesis, but the type-1 DM model predominantly in the rostral brain. Rarefaction was accompanied by basement membrane thickening and perivascular collagen accumulation in type-1 DM; more severe blood-brain barrier leakage, and disruption of perivascular ECM organization, mainly of elastin and collagen fibers' structural integrity in the HFHS model. Our results point out that the downstream mechanisms of the long-term vascular complications of hyperglycemia models are structurally distinctive and may have implications for appropriate treatment options.

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

Perivascular PDGFRB+ cells accompany lesion formation and clinical evolution differentially in two different EAE models.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that may lead to progressive disability. Here, we explored the behavioral pattern and the role of vasculature especially PDGFRB+ pericytes/ perivascular cells, in MS pathogenesis. METHODS: We have evaluated vascular changes in two different experimental allergic encephalomyelitis (EAE) mice models (MOG and PLP-induced). PDGFRB+ cells demonstrated distinct and different behavioral patterns. In both models, fibrosis formation was detected via collagen, fibronectin, and extracellular matrix accumulation. RESULTS: The PLP-induced animal model revealed that fibrosis predominantly occurs in perivascular locations and that PDGFRB+ cells are accumulated around vessels. Also, the expression of fibrotic genes and genes coding extracellular matrix (ECM) proteins are upregulated. Moreover, the perivascular thick wall structures in affected vessels of this model presented primarily increased PDGFRB+ cells but not NG2+ cells in the transgenic NG2-DsRed transgenic animal model. On the other hand, in MOG induced model, PDGFRB+ perivascular cells were accumulated at the lesion sites. PDGFRB+ cells colocalized with ECM proteins (collagen, fibronectin, and lysyl oxidase L3). Nevertheless, both MOG and PLP-immunized mice showed increasing EAE severity, and disability parallel with enhanced perivascular cell accumulation as the disease progressed from earlier (day 15) to later (day 40). CONCLUSION: As a result, we have concluded that PDGFRB+ perivascular cells may be participating in lesion progression and as well as demonstrating different responses in different EAE models.

Investigation of Factors Affecting the Side of the Disease Onset in Parkinson's Disease.

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disease that starts unilaterally in almost all cases and tends to emerge on the side of the dominant hand, but what we know about the cause of this lateralization is limited. Frequent use of the extremity and physical activity are argued to be protective from PD in preclinical and clinical studies. This study aimed to evaluate the effect of handedness and working in occupations that require continuous use of upper extremities on the disease onset-side. Methods: We retrospectively collected 84 PD patients who applied to Koç University Neurology outpatient clinic between July 2016-October 2018. We analyzed the parameters of the side and region of disease onset, age of onset, number of drugs used for PD, hand preference, and patients' occupations. Results: The median age of our study group was 61 (53-69). Thirty (36%) of the 84 patients were women. Seventy-nine patients (94%) were right-handed. Eighty-three (99%) had asymmetric onset. The disease started on the dominant hand side in 47 patients (57%) and on the non-dominant hand side in 36 (43%) patients. In our group with a median disease duration of four (2-7) years, the side with more severe complaints measured with the Unified Parkinson's Disease Evaluation Scale was consistent with the onset-side of the disease (p<0.001). In addition, the number of drugs used for PD and the scale score were higher in patients with longer disease duration (p=0.039, p=0.005). The number of drugs used for PD was also higher in patients with lower extremity-onset or both upper and lower extremities affected simultaneously than the upper extremity-onset (p=0.005). While the probability of starting on the dominant side was 43% in patients working in occupations requiring continuous use of upper extremities, it was 65% in others (p=0.027). Conclusion: According to this study, the onset of PD tends to be on the dominant hand side. Continuous upper extremity use may reduce the possibility of starting on the dominant side.

Evaluation of the Inferior Vena Cava Diameter in Dehydrated Children Using Bedside Ultrasonography.

Objective: Bedside ultrasonography (US) is a new imaging modality that has begun to be used in the Pediatric Emergency Unit to evaluate inferior vena cava (IVC) diameter for intravascular volume status. In this article, we aimed to evaluate IVC diameter with bedside US before and after the fluid therapy in dehydrated children. Methods: A total of 124 dehydrated patients were enrolled, aged 8 months to 17 years. The maximum diameters of the IVC and aorta (AO) were measured. IVC/AO ratio and IVC collapsibility index IVC-CI were calculated before and after the fluid therapy and correlation with the degree of dehydration and laboratory parameters was investigated. Results: Of the 124 patients, 49.2% (n = 61) were male, the mean age was 7.5 ± 4.94 years. The IVC/AOs ratio was increased in mild and moderate/severe groups after fluid therapy compared to before fluid administration. While the mean rate of heart rate, blood urea nitrogen (BUN), creatinine, and uric acid values were higher in the moderate/severe group, potassium and HCO3 were lower. There was no significant change in AO diameter and IVC-CI after fluid therapy in all groups. When the factors affecting the IVC/AOs ratio were analyzed with the logistic regression backward model; the IVC/AO ratio was found to increase as the degree of dehydration decreased (Adj.ß = -0.318) and as the age (Adj.ß = 0.242) and CRP (Adj.ß = 0.186) value increased. Conclusion: The IVC/AO ratio can be a promising index for the assessment and grading of dehydration in children, and cutoff values that vary according to age are necessary for a more objective assessment of dehydration.

Evaluation of Serum Omentin-1, Vaspin, Leptin, Adiponectin Levels in Obese/Overweight Children and Their Relationship With Non-Alcoholic Fatty Liver Disease.

To investigate adipokines (vaspin, omentin-1, adiponectin and leptin) and their correlation with hepatosteatosis degree in obese/overweight (O/O) children. We analyzed adipokine levels of 81 children (49 O/O, [body mass index (BMI) > 95th] and 32 non-obese (BMI = 5-85th) admitted to the pediatric outpatient clinic. Serum triglyceride, glucose, low density lipoprotein-cholesterol, total cholesterol, high density lipoprotein-cholesterol, alanine aminotransferase, aspartate aminotransferase (AST), insulin, HbA1c levels and leptin, omentin-1, vaspin, adiponectin levels were studied. O/O children with hepatosteatosis were divided into grades 1, 2 and 3 according to the degree of hepatosteatosis determined by ultrasonography. While AST (p = 0.001), triglyceride (p = 0.006), BMI percentile (p = 0.000), HOMA index (p = 0.002), systolic blood pressure (p = 0.02), leptin (p = 0.001), omentin-1 (p = 0.001), adiponectin (p = 0.001) levels were higher, vaspin level was lower (p = 0.008) in the (O/O) group compared to the controls. There was a positive correlation between HDL and vaspin, and a negative correlation between HDL and omentin-1 in the O/O group. Also it was observed that as the degree of hepatosteotosis increased, leptin (p = 0.004), omentin-1 (p = 0.001) levels were increased. There was no significant change in vaspin level (p = 0.128). The high levels of omentin-1, leptin and adiponectin have an association with the development of hepatosteatosis in O/O children.

Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study.

BACKGROUND: During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. METHODS AND FINDINGS: Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1.30, 95% CI 1.16 to 1.45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1.10, 95% CI 1.08 to 1.12; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. CONCLUSIONS: Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. TRIAL REGISTRATION: ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258.

The Therapeutic Potential of Ethnomedicinally Important Anatolian Thyme Species: A Phytochemical and Biological Assessment.

Thyme has been used for various therapeutic purposes in many different cultures, which makes it one of the most riveting medicinal plants throughout history. From its beneficial effects on the respiratory tract or the gastrointestinal system, to its unique skin-related activities, the investigation of the medicinal properties of thyme has always been an alluring topic for researchers aiming to develop conventional medications from this traditional herb. With an incentive to contribute to the extensive thyme research, three Thymus L. species namely Thymus cariensis Hub-Mor. & Jalas (endemic), Thymus praceox subsp. grossheimii (Ronniger) Jalas, and Thymus pubescens Boiss. et Kotschy ex Celak from Turkey were deeply investigated within this study. The analysis of the phytochemical constituents of the extracts was conducted by LC-MS/MS. 12 biologically important secondary metabolites (p-coumaric acid, caffeic acid, salicylic acid, quinic acid, fumaric acid, vanillin, malic acid, rutin, apigenin, naringenin, and nicotiflorin) were detected in all extracts. Their total phenolic and flavonoid contents were calculated (11.15 ± 0.17-61.12 ± 2.59 µg PEs/mg extract, 2.53 ± 0.04-40.28 ± 0.92 µg QEs/mg extract, respectively), and the antioxidant potential of the extracts was evaluated by DPPH and ABTS radical scavenging and CUPRAC activity methods, accordingly, the extracts were shown to possess significant antioxidant activity. Among them, Thymus cariensis Hub-Mor. & Jalas was the most active with IC50 values of 34.97 ± 1.00 µg/ml and 9.98 ± 0.04 µg/ml regarding the DPPH and ABTS radical scavenging assays, respectively, and an A0.5 value of 5.80 ± 0.02 µg/ml according to CUPRAC activity method. Their anticholinesterase, antityrosinase, and antiurease activities were also tested, Thymus cariensis Hub-Mor. & Jalas (35.61 ± 1.20%) and Thymus pubescens Boiss. et Kotschy ex Celak aerial part extract (33.49 ± 1.39%) exhibited moderate antibutyrylcholinesterase activity at 200 µg/ml concentration. The results of the cell viability assay indicated that the extracts demonstrated moderate-to-low cytotoxicity on A498 human renal cell lines. Furthermore, all studied extracts exerted noteworthy antimicrobial activity, especially against Candida tropicalis (MIC values: 19.53-78.12 µg/ml). The presented data substantiates the use of thyme extracts as therapeutic agents in both ethnomedicine and conventional therapies.