The Role of RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 Single-nucleotide Polymorphisms in the Doxorubicin-induced Cardiotoxicity in Solid Childhood Tumors.

BACKGROUND: The objective of our study was to determine the role of retinoic acid receptor gamma (RARG) rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 single-nucleotide polymorphisms in identifying the risk of doxorubicin-induced cardiotoxicity in pediatric solid tumors. METHODS: A total of 60 pediatric patients who had completed their treatment at least 2 years ago and 50 healthy children matched for age and sex were included in the study. All patients were evaluated for cardiotoxicity by echocardiography. The blood samples were analyzed for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 polymorphisms. Demographic characteristics, echocardiographic parameters, and genetic results of both groups were evaluated. RESULTS: In our study, the RARG rs2229774 AA genotype was associated with cardiotoxicity ( P =0.017). The SLC28A3 rs7853758 AA+GA genotype was detected more frequently in patients who did not develop cardiotoxicity ( P <0.023). Furthermore, the frequency of the SLC28A3 rs7853758 A allele was significantly lower in the cardiotoxicity group ( P <0.025). CONCLUSIONS: This is the first study in the Turkish population to investigate the correlation between the cardiotoxicity risk and 3 marker genes, which are recommended in the pharmacogenetic guideline for risk assessment in pediatric doxorubicin patients. The gene polymorphism that we investigated in this study was useful for the early prediction of cardiotoxicity risk.

Autonomic activity and cardiovascular system risk assessment in pediatric patients with hemolytic uremic syndrome.

In pediatric patients with hemolytic uremic syndrome (HUS), cardiac involvement and autonomic nervous system function can be evaluated by a non-invasive method called heart rate variability (HRV). This study aims to evaluate heart rate variability and electrocardiography findings in patients with HUS by comparing a healthy group. Patients who are diagnosed with HUS at a university hospital from December 2020 to June 2022 are screened by electrocardiography (ECG), echocardiography, and 24-h Holter ECG. A healthy control group, compatible in age and gender with the patient group, was selected from healthy subjects. HRV parameters, laboratory values, and ECG findings were analyzed and compared with the healthy group and each other. There were 25 patients with HUS and 51 participants in the healthy control group. Statistically significant differences were found in some HRV parameters: standard deviation of normal to normal intervals, the mean of the 5-min RR interval standard deviations, the standard deviation of 5-min RR interval means, the triangular interpolation of normal to normal interval, and very-low-frequency power. HUS patients had impaired and declined HRV values compared to the healthy group. There was a significant decrease in the PR distance, while a significant increase in the corrected QT and QT dispersion values was detected in the electrocardiographic findings of the patient group. HRV values impaired as renal failure parameters increased.  Conclusion: Patients with HUS may have autonomic nervous system dysfunction. HRV measurement is a non-invasive method that can evaluate this. It can be thought that there may be an increased risk of cardiovascular events and arrhythmias in some patients with HUS. ECG should be also considered to detect arrhythmia. What is Known: • Hemolytic uremic syndrome (HUS) primarily effects the hematologic parameters and kidney. • Secondary cardiomyopathy with hypertension and renal failure could be observed in these patients. • Rhythm problems are not expected primarily in these patients. • There is very limited data in evaluating autonomic function and arrhythmia risk for these patients. What is New: • Patients with HUS may have autonomic nervous system dysfunction. • HRV measurement is a non-invasive method that can evaluate this. • Cardiovascular events and arrhythmias due to the deterioration of the balance between the sympathetic and parasympathetic systems could manifest in patients with HUS. • An ECG and screening patients for cardiac events, and monitoring them closely should be considered.

Assessing autonomic activity and prognostic risk factors comparing multisystem inflammatory syndrome and isolated viral myocarditis/myopericarditis.

INTRODUCTION AND AIM: In pediatric multisystem inflammatory syndrome and isolated viral myocarditis/myopericarditis, autonomic nervous system function can be evaluated by a non-invasive method called heart rate variability. This study aims to evaluate heart rate variability in these two groups by comparing them with each other. This is the first study assessing these values in these two groups of patients. METHOD: Patients who are diagnosed with multisystem inflammatory syndrome in children and isolated viral myocarditis/myopericarditis at a university hospital from September 2021 to February 2023 are screened by electrocardiography, echocardiography, and 24-hour Holter monitoring. A healthy control group, compatible in age and gender with the patient groups, was selected from healthy subjects that applied to the hospital for palpitation, murmur, and/or chest pain. Heart rate variability parameters and related laboratory markers were analyzed and compared among the three groups. RESULTS: There were 30 patients with multisystem inflammatory syndrome in children, 43 patients with isolated viral myocarditis/myopericarditis, and 109 participants in the healthy control group. Statistically significant differences were found in most of the heart rate variability parameters: standard deviation of normal to normal intervals (SDNN), the mean of the 5- minute RR interval standard deviations (SDNNI), the standard deviation of 5-minute R wave to R wave(RR) interval means (SDANN), the root mean square of successive RR interval differences (RMSSD), and the percentage of the beats with a consecutive RR interval difference of more than 50 ms (pNN50%), very low frequency, high frequency, low frequency, triangular index, and low frequency/high-frequency ratio. Multisystem inflammatory syndrome in children patients had impaired and declined heart rate variability values compared to the other two groups. In patients with myocarditis/myopericarditis, we couldn't find a significant difference in these parameters with the control group. CONCLUSION: Heart rate variability can be used as an important non-invasive autonomic function parameter in determining prognosis and treatment plans, especially in patients diagnosed with multisystem inflammatory syndrome in children. This impairment of autonomic activity could be more prominent in patients with decreased left ventricular systolic functions.

The effect of video-assisted training on upper extremity problems and functions after rotator cuff repair: a randomized controlled trial.

Background/aim: The shoulder is the most mobile joint in the body, and is frequently exposed to injuries. The applied surgical treatments, protection of the shoulder after surgery, care in the use of the shoulder in activities of daily living (ADLs) and gradual exercise programs are all vital to the recovery process. The present study investigates the effect of video-assisted training (VAT) on upper extremity complications and functions after rotator cuff repair (RCR). Materials and method: Included in this prospective, parallel two-armed, randomized controlled study were an experimental group (n: 24) that received VAT detailing early postoperative care for RCR and instructions on performing ADLs, and that had access to a 90-day gradual exercise program, and a control group (n: 24) that received routine care. The primary outcomes were upper extremity problems and functions, as assessed by the Disabilities of the Arm, Shoulder and Hand (DASH) and modified Constant-Murley scores (MCM), while secondary outcomes were complications that had developed within the past three months. The outcomes were measured at baseline, after six weeks and at three months. Results: After 3 months, a statistically significant difference was noted in the DASH-Work (p = 0.001) and MCM ADLs scores (p = 0.003) of the two groups, and significant changes in which the scale scores of both groups when compared to the initial measurement. Only one patient in the VAT group developed complications after RCR at one month; there were no significant differences in the complications of the two groups (p = 0.235). Conclusion: VAT can increase function in RCR patients. Healthcare professionals, especially nurses, can use the VAT method to improve shoulder function in patients after RCR.

Peri-ictal headache: An underestimated prognostic finding associated with idiopathic epilepsies.

OBJECTIVE: There are a handful of studies investigating peri-ictal headache (PIH) and its clinical associations in patients with idiopathic/genetic epilepsies (I/GE). This multi-center study aimed to investigate PIH, which is an ignored comorbid condition in patients with I/GE, by headache experts and epileptologists working together. METHODS: The data were collected from a cross-sectional large study, using two structured questionnaires for headache and epilepsy features, fulfilled by neurologists. Headaches were classified according to the International Classification of Headache Disorders, third edition, whereas seizure and syndrome types were diagnosed according to International League Against Epilepsy criteria. The patients with a headache starting 24 hours before the onset of the seizure (preictal) or within 3 hours after the seizure (postictal) were defined as patients with PIH. We compared demographic and clinical differences between two groups of patients with and without PIH statistically and used ROC curves to determine a threshold of the total number of seizure triggers associated with the occurrence of PIH. RESULTS: Among 809 (531 females, 65.6%) consecutive patients with I/GE, 105 (13%) patients reported PIH (22 preictal, 82 postictal headaches, and one with both types). Peri-ictal headache was more frequently reported by females and those having a family history of migraine or epilepsy, and it was significantly associated with lower rates of seizure freedom for more than five years, drug resistance, and use of polytherapy, remarkably. Moreover, ROC curves showed that having more than 3 seizure triggers was associated with the presence of PIH. CONCLUSION: Our findings revealed that PIH may be linked to poor outcomes in I/GEs and seems to be related to a lower ictal threshold precipitated by multiple triggers. Future prospective studies will illuminate the unknown underlying mechanisms and appropriate management strategies for PIH to improve the prognosis.

The Efficacy of Physical Therapy and Rehabilitation Approaches in Chronic Migraine: A Systematic Review and Meta-Analysis.

BACKGROUND: Pharmacological treatment is the primary approach in chronic migraine (CM), although non-drug interventions such as physical therapy are used as adjunct treatments. We aimed to review the efficacy of physical therapy and rehabilitation approaches for CM and their impact on quality of life (QoL) and disability. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included randomized controlled trials (RCTs) in adults with CM. The primary outcomes were changes in intensity, frequency, duration of headache, disability, and QoL. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Data synthesis and quantitative analysis were conducted on relevant studies. RESULTS: Seven RCTs were included in the narrative review, and five of them were eligible for quantitative analysis. Aerobic exercise (AE), osteopathic manipulative treatment (OMT), occipital transcutaneous electrical stimulation (OTES), acupressure, hydrotherapy, instrument-assisted soft tissue mobilization (IASTM), facial proprioceptive neuromuscular facilitation (FPNF), and connective tissue massage (CTM) were used in CM. AE combined with pharmacological therapy reduced the frequency, duration, and intensity of headache. OMT combined with medication improved QoL and reduced disability, intensity of pain, and migraine days per month. Hydrotherapy combined with medication also resulted in improvements in the intensity of headache, frequency, and overall QoL. IASTM and OTES reduced the intensity of headache, alleviated neck pain, and improved QoL, although there were conflicting findings following OTES alone on disability and intensity of headache. Both FPNF and CTM reduced the intensity of headache. Acupressure as an adjunct to medication did not show additional benefits on the intensity of headache and QoL. Quantitative analysis of the data showed that manual physical therapy combined with medication reduced the intensity of headache (p = 0.0796), and manual or AE combined with medication reduced the headache days per month (p = 0.047). CONCLUSIONS: A limited number of RCTs investigating the efficacy of physical therapy and rehabilitation approaches show promise in improving headache symptoms, reducing disability, and enhancing QoL in CM. Meta-analysis of the data also supported favorable outcomes for both intensity and headache days per month. Further research is needed to better understand the efficacy, optimal duration, and safety of physical therapy and rehabilitation approaches for CM, and to explore alternative interventions.

Wound healing activity of Salvia huberi ethanolic extract in streptozocin-induced diabetic rats.

Objective: The aim of this study was to examine the in vivo wound healing potential of Salvia huberi Hedge (endemic to Turkey) on excision and incision wound models in diabetic rats. Method: Male Wistar albino rats, 3-4 months old and weighing 180-240g were used. The animals were randomly divided into five groups including Control, Vehicle and Fito reference, and two different concentrations (0.5% and 1% weight/weight (w/w)) of ethanol extract of Salvia huberi were investigated in both wound models on streptozocin-induced diabetic rats using macroscopic, biomechanical, biochemical, histopathological, genotoxic and gene expression methods over both seven and 14 days. Fito cream (Tripharma Drug Industry and Trade Inc., Turkey) was used as the reference drug. Results: A total of 60 rats were used in this study. Salvia huberi ointments at 0.5% and 1% (w/w) concentrations and Fito cream showed 99.3%, 99.4% and 99.1% contraction for excision wounds, and 99.9%, 97.0% and 99% contraction for incision wounds, respectively. In Salvia huberi ointments and Fito cream groups, re-epithelialisation increased dramatically by both day 7 and day 14 (p<0.05). By day 14, low hydroxyproline and malondialdehyde (MDA) levels, and high glutathione (GSH) levels were observed in the Salvia huberi ointment groups. After two application periods, damaged cell percent and genetic damage index values and micronucleus frequency of Salvia huberi ointment treatment groups were lower than Control and Vehicle groups (p<0.001). A growth factor expression reached a high level by day 7 in the Control group; in Salvia huberi-treated groups it was decreased. Conclusion: The study showed that application of Salvia huberi ointments ameliorated the healing process in diabetic rats with excisional and incisional wounds and may serve as a potent healing agent.

COVID-19 vaccination-related headache showed two different clusters in the long-term course: a prospective multicenter follow-up study (COVA-Head Study).

BACKGROUND: Although acute headache following COVID-19 vaccination is widely acknowledged, the long-term progression of these headaches remains poorly understood. Our objective was to identify various phenotypes of prolonged or worsened headaches associated with COVID-19 vaccination and document any changes in these phenotypes over an extended period. Additionally, we aimed to document the diverse headache presentations among patients with pre-existing primary headaches. METHODS: A multinational, prospective observational study was conducted to investigate prolonged or worsened headaches associated with COVID-19 vaccination. Questionnaires assessing COVID-19 vaccination-related headaches at three time points (initial visit, 3rd month follow-up, and 6th month follow-up) were developed for the study. Headache specialists/clinicians evaluated patients using these questionnaires in a prospective manner. Repeated K-means cluster analysis was performed to identify patient profiles with prolonged or worsened headaches related to COVID-19 vaccination. RESULTS: Among the 174 patients included in the study, there was a female-to-male ratio of 128 (73.6%) to 46 (26.4%). The mean age of the patient group was 45.2 ± 13.3 years, and 107 patients (61.5%) had a pre-existing history of primary headaches. Through the analysis, two major clusters were identified based on headache characteristics at each visit. During the first visit (n = 174), Cluster 1 primarily comprised patients with a history of primary headaches, frontal localization of pain, throbbing pain type, more severe headaches accompanied by symptoms such as nausea, phonophobia, photophobia, and osmophobia, and worsened by physical activity. In contrast, Cluster 2 consisted of patients with longer headache durations (over one month) and a stabbing/pressing quality of pain. Patients in Cluster 1 had a higher prevalence of migraine as the pre-existing primary headache disorder compared to Cluster 2 (90.48% vs. 68.18%, respectively; p = 0.005). CONCLUSION: The identification of two distinct phenotypes of prolonged or worsened headaches related to COVID-19 vaccination can provide valuable clinical insights. Having an awareness of the potential worsening of headaches following COVID-19 vaccination, particularly in patients with a primary headache disorder such as migraine, can help clinicians and headache experts anticipate and adjust their treatment strategies accordingly. This knowledge can aid in preplanning treatment modifications and optimize patient care.

Investigation of the relationship between periodontal and systemic inflammation in children with Sickle Cell Disease: A case- control study.

Periodontal diseases are chronic inflammatory diseases and tissue destruction increases with oxidative stress in periodontal tissues. Periodontal diseases are associated with systemic diseases such as diabetes, cardio-vascular diseases and rheumatoid arthritis by means of systemic inflammation. Sickle cell disease (SCD) is a chronic inflammatory disease in which vaso-occlusive crisis and endothelial dysfunction are present. It is not known whether the chronic systemic inflammation seen in SCD affect periodontal tissues. The aim of this study was to investigate the relationship between periodontal and systemic inflammation in children with SCD. Forty-three children with SCD and 43 healthy children were included in the study. Physical, dental and periodontal statuses were examined, blood and saliva samples were taken. Levels of pro-inflammatory and oxidative stress mediators in serum and saliva were evaluated. The periodontal findings of the groups were similar. The majority of the subjects in both groups had gingival inflammation. In SCD group, significantly higher serum high sensitive C-reactive protein (Hs-CRP), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, total oxidant status (TOS), nitric oxide (NO) and salivary IL-6 were observed (p < 0.05). There were positive correlations between salivary IL-6 levels and serum Hs-CRP levels (r = 0.303, p < 0.05). In addition; it was determined that salivary IL-6, TNF-α and NO levels were increased 3-6 times in children with a history of painful crisis or acute chest syndrome compared to children who had never had a painful crisis or acute chest syndrome. Although, observed oral health status was similar in both groups, salivary cytokine levels were increased in children with SCD. The higher salivary cytokine levels may be associated with chronic systemic inflammation and vaso-occlusion observed in children with SCD.

Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

miR-181a-5p is a potential candidate epigenetic biomarker in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal degeneration. Abnormal expression of microRNAs (miRNAs) plays an important role in MS pathology. In this cohort study, differential expression of the four miRNAs (hsa-miR-155-5p, hsa-miR-9-5p, hsa-miR-181a-5p, and hsa-miR-125b-5p) was investigated in 69 individuals, including 39 MS patients (relapsing-remitting MS (RRMS), n = 27; secondary progressive MS (SPMS), n = 12) and 30 healthy controls. In silico analyses revealed possible genes and pathways specific to miRNAs. Peripheral blood miRNA expressions were detected by quantitative real-time PCR (qPCR). hsa-miR-181a-5p was downregulated and associated with increased MS risk (P = 0.012). The other three miRNAs were upregulated and not associated with MS (P < 0.05). The area under the curve (AUC) is 0.779. In silico analyses showed that hsa-miR-181a-5p may participate in MS pathology by targeting MAP2K1, CREB1, ATXN1, and ATXN3 genes in inflammation and neurodegeneration pathways. The circulatory hsa-miR-181a-5p can regulate target genes, reversing the mechanisms involved in MS pathologies such as protein uptake and processing, cell proliferation and survival, inflammation, and neurodegeneration. Thus, this miRNA could be used as an epigenomic-guided diagnostic tool and for therapeutic purpose.

Effect of abdominal massage on bowel evacuation in neurosurgical intensive care patients.

BACKGROUND: There are many factors, which affect the bowel evacuation of neurosurgical intensive care unit (NICU) patients, resulting in constipation. AIM AND OBJECTIVES: The aim of this study was to investigate effect of abdominal massage on bowel evacuation and the risk of constipation in NICU patients. DESIGN: A prospective, randomized-controlled clinical trial. METHODS: The sample of this study included 80 NICU patients. The patients were randomly assigned to abdominal massage and control groups. The constipation risk of all the patients was assessed with Constipation Risk Assessment Scale (CRAS). The patients in the abdominal massage group received a total of 30 minutes of massage, 15 minutes every morning and evening, until the first defecation. The bowel sounds of all patients in the abdominal massage and control groups were assessed on a daily basis. The days when bowel sounds were heard and the first defecation took place were recorded in a Bowel Evacuation Form. RESULTS: The risk of constipation was higher in the patients in the abdominal massage (CRAS score 19.02 ± 1.81) and control groups (CRAS score 20.45 ± 2.61). The time of return of bowel sounds and the time of the first defecation were earlier in the abdominal massage group, compared to the control group (P < .05). In the control group, there was a weak correlation (P = .004) between the CRAS score and the time of return of bowel sounds, while there was a moderate correlation between the CRAS score and the time of the first defecation (P < .001). CONCLUSION: Our study results show that the risk of constipation is high in NICU patients, and abdominal massage is an effective nursing intervention to shorten the time of return of bowel sounds and the time of the first defecation. RELEVANCE TO CLINICAL PRACTICE: Nurses can safely apply abdominal massage to improve bowel evacuation in NICU patients.

Latent class cluster analysis identified hidden headache phenotypes in COVID-19: impact of pulmonary infiltration and IL-6.

BACKGROUND AND OBJECTIVE: Clinical studies on COVID-19 headache are limited. This prospective study aimed to define headache characteristics, associated clinical and laboratory factors, and treatment response in COVID-19. METHODS: Cross-sectional study enrolled 287 patients diagnosed with COVID-19 and hospitalized on a regular ward during the pandemic. All patients were examined face to face and followed by a neurologist during their stay in the hospital. The characteristics, concomitant symptoms, treatment responses, and laboratory findings of COVID-19-associated headaches were recorded. RESULTS: Eighty-three COVID-19 patients reported headache (28.9%), in which 85.5% had no prior headaches. Mean age was 48.40 ± 15.90 and 58% was men. Compared to COVID-19 patients without headache (n = 204), patients with headache showed significantly higher frequency of pulmonary involvement (76%) and increased D-dimer levels. Fifty-nine percent of headaches responded iv paracetamol 1000 mg, and 85% of the paracetamol unresponsive headaches were relieved by greater occipital nerve (GON) blocks. Latent class cluster analysis identified 2 distinct class of bilateral, frontal, throbbing headaches: severe (VAS > 84), longer (> 14 h), frequent (> 7 headache days), paracetamol unresponsive-GON responsive headaches (85%), with pulmonary involvement (100%), and higher IL-6 levels (> 90 pg/mL) were classified in cluster 1. Cluster 2 included moderately affected patients (VAS > 54, > 6 h, > 4 days, 60% pulmonary involvement, > 20 pg/mL IL-6) and paracetamol responsive headaches (96%). VAS scores showed positive linear correlation with IL-6 levels (p < 0.001; r = 0.567). CONCLUSION: The intensity, duration, frequency, bilateral frontal location, and treatment response of COVID-19 headache was related to pulmonary involvement and IL-6 levels, which indicated a role of inflammation in determining the headache manifestations in moderately affected hospitalized patients. ROC curve cutoff values pointed that VAS > 70 severity, > 9 h duration, > 5 headache days, and IL-6 > 43 pg/mL levels can be diagnostic for COVID-19 headache. GON blocks can effectively abort headache when patients are unresponsive to paracetamol, and other NSAIDs are avoided during the SARS-CoV-2 infection.

Long-term cognitive outcomes of prematurely born infants: A longitudinal follow-up of Denver II, Bayley III and WISC-IV Tests.

BACKGROUND: Prematurity constitutes a risk factor for developmental delay in infancy and childhood. This study aims to: (i) determine long-term cognitive outcomes in prematurely delivered children and compare them with term-delivered children using the WISC-IV and Stroop tests; (ii) examine the relation between Denver II, Bayley III and WISC-IV, Stroop tests. METHODS: The study group consisted of children born prematurely who had been tested with Denver II and Bayley III in their first 2 years, and had been evaluated with WISC-IV and Stroop tests under follow up, 6-10 years later. RESULTS: The study group (n = 60, 25 F, 35 M) was 8.0 ± 2.4 (6-10.7) years old when given WISC-IV and Stroop tests. Gestational age in the study group was 34-37 weeks in 25%, 30-33 weeks in 48.3%, and <29 weeks in 26.7%. On WISC-IV, the verbal comprehension index, perceptual reasoning index, working memory index, and full-scale IQ scores were lower in the study group than the control group (P < 0.05). The study group took longer to complete the Stroop test (P < 0.05). Lower socioeconomic status (P = 0.005) and parental education level (P = 0.000) were associated with lower verbal comprehension index scores. Denver II and Bayley III test results were related to WISC-IV results (P < 0.05) but not to the Stroop test results (P > 0.05). CONCLUSIONS: Our results showed prematurity negatively influences the results of WISC-IV and Stroop tests at school age. Denver II and Bayley III tests applied at age 2 years likely predict WISC-IV results.

The effects of pulsed electromagnetic field on experimentally induced sciatic nerve injury in rats.

Some experimental research indicates that low-frequency pulsed electromagnetic field (PEMF) stimulation may accelerate regeneration in sciatic nerve injury. However, little research has examined the electrophysiological and functional properties of regenerating peripheral nerves under PEMF. The main aim of the present study is to investigate the effects of PEMF on sciatic nerve regeneration in short- and long-term processes with electrophysiologically and functionally after crushing damage. Crush lesions were performed using jewelery forceps for 30 s. After crush injury of the sciatic nerves, 24 female Wistar-Albino rats were divided into 3 groups with 8 rats in each group: SH(Sham), SNI (Sciatic Nerve Injury), SNI+PEMF(Sciatic Nerve Injury+Pulsed Electromagnetic Field). SNI+PEMF group was exposed to PEMF (4 h/day, intensity; 0.3mT, low-frequency; 2 Hz) for 40-days. Electrophysiological records (at the beginning and 1st, 2nd, 4th and 6th weeks post-crush) and functional footprints (at 1st, 2nd, 3rd, 4th, 5th and 6th weeks post crush) were measured from all groups during the experiment. The results were compared to SNI and SNI+PEMF groups, it was found that amplitude and area parameters in the first-week were significantly higher and latency was lower in the SNI+PEMF group than in the SNI group (p < 0,05). However, the effect of PEMF was not significant in the 2nd, 4th, 6th weeks. In addition, in the 1st and 2nd weeks, the SSI parameters were significantly higher in SNI+PMF group than SNI group (p < .05). These results indicate that low-frequency PEMF is not effective for long-periods of application time while PEMF may be useful during the short-term recovery period.

HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism.

BACKGROUND AND AIM: Pathogenesis of COVID-19 -related headache is unknown, though the induction of the trigeminal neurons through inflammation is proposed. We aimed to investigate key systemic circulating inflammatory molecules and their clinical relations in COVID-19 patients with headache. METHODS: This cross-sectional study enrolled 88 COVID-19 patients, hospitalized on a regular ward during the second wave of the pandemic. Clinical characteristics of COVID-19 patients were recorded, and laboratory tests were studied. RESULTS: The mean ages of 48 COVID-19 patients with headache (47.71 ± 10.8) and 40 COVID-19 patients without headache (45.70 ± 12.72) were comparable. COVID-19 patients suffered from headache had significantly higher serum levels of HMGB1, NLRP3, ACE2, and IL-6 than COVID-19 patients without headache, whereas CGRP and IL-10 levels were similar in the groups. Angiotensin II level was significantly decreased in the headache group. COVID-19 patients with headache showed an increased frequency of pulmonary involvement and increased D- dimer levels. Furthermore, COVID-19 was more frequently associated with weight loss, nausea, and diarrhea in patients with headache. Serum NLRP3 levels were correlated with headache duration and hospital stay, while headache response to paracetamol was negatively correlated with HMGB1 and positively associated with IL-10 levels. CONCLUSION: Stronger inflammatory response is associated with headache in hospitalized COVID-19 patients with moderate disease severity. Increased levels of the circulating inflammatory and/or nociceptive molecules like HMGB1, NLRP3, and IL-6 may play a role in the potential induction of the trigeminal system and manifestation of headache secondary to SARS-CoV-2 infection.

Altered VEGF, Bcl-2 and IDH1 expression in patients with adenomyosis.

PURPOSE: Adenomyosis is a benign uterine disease resulting from the myometrial invasion of the endometrial gland and stroma. In the current study, angiogenesis, apoptosis and energy metabolism were investigated in adenomyosis. METHODS: A retrospective study was performed using paraffin archival tissues. Three groups were included in the study: Group I and Group II; ectopic and eutopic endometrial tissues of patients with adenomyosis, respectively, and Control Group; endometrial tissue of individuals without adenomyosis. Vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), intercellular adhesion molecule 1 (ICAM-1) and hypoxia-inducible factor 1 alpha (HIF-1A) levels were evaluated as angiogenic markers. Bcl-2, caspase-9 and caspase-3 levels were investigated as apoptotic indicators, and isocitrate dehydrogenase 1 (IDH1), succinate dehydrogenase complex subunit C (SDHC) and fumarate hydratase (FH) levels were also examined as energy metabolism markers. Gene expression levels of all parameters were determined by RT-PCR. RESULT: VEGF expression levels were found to be increased in Group I according to the control group and Group II. Bcl-2 expression levels were found to be increased in the Group I compared to the Group II. It was determined that expression levels of IDH1 were decreased in the Group I and Group II compared to the Control Group. There was no significant difference in the other examined parameters. Although we did not find a significant difference in HIF-1A levels between the groups, we found a positive correlation between VEGF and HIF-1A in the Group I. CONCLUSION: These results point out that VEGF, HIF-1A, Bcl-2 and IDH1 may be associated with the etiology of adenomyosis.

The effect of metilpheniydate, risperidone and combination therapy on ECG in children with attention-deficit hyperactivity disorder.

INTRODUCTION: This study is to investigate ventricular repolarization on electrocardiogram (ECG) in a pediatric population receiving methylphenidate (MPH), risperidone (RIS) and combined therapy. METHODS: A total of 215 patients between 6 and 12years with ADHD/conduct disorder receiving methylphenidate, risperidone and combined therapy for minimum 3months and an untreated ADHD group (n=76) was consecutively included in the study. Twelve lead ECG parameters including mean QT, QTc, T-peak to T-end (TpTe) intervals, TpTe dispersion and TpTe/QT ratio were compared. RESULTS: QT interval, and QTc, TpTe interval, TpTe dispersion and TpTe/QTc ratio values for groups receiving RIS, MPH and combined therapy were found to be significantly higher than other groups. Moreover, in the combined therapy group TpTe and TpTe/QTc values were higher than the single drug administration groups (p<0.05). TpTe and TpTe/QT ratio was significantly higher in the RIS group compared to that of the MPH group. CONCLUSION: These results suggested that combined therapy of these drugs had a more prominent impact on the T wave and RIS could be strongly associated with it.

Atopic disorders are more common in childhood migraine and correlated headache phenotype.

BACKGROUND: The supportive clinical and pathophysiological data about the correlation between migraine and atopic disorders are far from a coincidence. In order to determine and investigate the correlates of atopic disorders in a specific dataset, we performed this retrospective cross-sectional clinical-based study. METHODS: The dataset was composed from three tertiary center web-based databases (http://www.childhoodheadache.org). Headache diagnosis and differential diagnosis were made according to the International Classification of Headache Disorders, 2nd version and the Diagnostic Statistical Manual of Mental Disorders, 5th edition. Migraine with aura, migraine without aura, chronic migraine and episodic and chronic tension type headache (TTH) patients were included. All other causes of headache disorders, including comorbid headache disorders like migraine plus TTH or "possible" causes of headache, were excluded. RESULTS: The study included 438 patients with migraine and 357 patients with TTH, whose age and sex distribution were identical. After descriptive statistics accordingly, 80 migraine (18.2%) and 23 TTH (6.4%) patients were found to have specific atopic disorders (P < 0.001). Atopic disorders are more commonly reported in patients with migraine with aura (21.6%) than those with migraine without aura and TTH (P < 0.001). The most common atopic disorders were seasonal rhinitis, conjunctivitis and asthma. There was also a close correlation between TTH with atopic disorders and psychiatric comorbid disorders of the patients. CONCLUSIONS: Although the International Classification of Headache Disorders, 2nd version, does not specify, atopic disorders should be suspected in all migraine patients and their relatives, not only for accurate diagnosis but also for planning prophylactic medications, such as ß-blockers.

Role of luteal phase support on gonadotropin ovulation induction cycles in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of luteal phase progesterone support on pregnancy rates in women with polycystic ovary syndrome (PCOS) who were treated for clomiphene citrate-resistant anovulatory infertility with ovulation induction and intrauterine insemination (OI/ IUI). STUDY DESIGN: This randomized study included 110 clomiphene citrate-resistant PCOS patients. All patients underwent ovulation induction with recombinant follicle-stimulating hormone and intrauterine insemination, up to 3 cycles, and were randomized into 2 groups: (1) luteal support with progesterone or (2) a control group. The main outcomes were clinical pregnancy rates and live birth rates per cycle. RESULTS: Demographic data were not different between the study and control groups. Cycle characteristics were found to be homogeneous between groups. A total of 38 pregnancies were achieved (15.5% pregnancy rate per cycle). The clinical pregnancy rate and live birth rate per cycle in progesterone supported cycles were 18.9% and 16.8%, respectively. CONCLUSION: There might be a clinical benefit of luteal progesterone supplementation on OI/IUI cycles for women with PCOS. Although we did not reach a statistically significant difference between the 2 groups, luteal-supported cycles demonstrated a 6.7% higher clinical pregnancy rate and 6.1% higher live birth rate.