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Mesoporous silica nanoparticles (MSNs) are inorganic nanocarriers presenting versatile properties and the possibility to deliver drug molecules via different routes of application. Their modification with lipids could diminish the burst release profile for water-soluble molecules. In the case of oleic acid (OA) as a lipid component, an improvement in skin penetration can be expected. Therefore, in the present study, aminopropyl-functionalized MSNs were modified with oleic acid through carbodiimide chemistry and were subsequently incorporated into a semisolid hydrogel for dermal delivery. Doxorubicin served as a model drug. The FT-IR and XRD analysis as well as the ninhydrin reaction showed the successful preparation of the proposed nanocarrier with a uniform particle size (352–449 nm) and negative zeta potential. Transmission electron microscopy was applied to evaluate any possible changes in morphology. High encapsulation efficiency (97.6 ± 1.8%) was achieved together with a sustained release profile over 48 h. The composite hydrogels containing the OA-modified nanoparticles were characterized by excellent physiochemical properties (pH of 6.9; occlusion factor of 53.9; spreadability of factor 2.87 and viscosity of 1486 Pa·s) for dermal application. The in vitro permeation study showed 2.35 fold improvement compared with the hydrogel containing free drug. In vitro cell studies showed that loading in OA-modified nanoparticles significantly improved doxorubicin’s cytotoxic effects toward epidermoid carcinoma cells (A431). All of the results suggest that the prepared composite hydrogel has potential for dermal delivery of doxorubicin in the treatment of skin cancer.

Introduction: Acute hemiparesis is an emergency of various etiologies and possible fatal outcome. Aim: The aim of this study was to determine the etiology, clinical manifestations, and prognosis of acute hemiparesis in childhood. Materials and methods: This is a retrospective study of 52 children (28 boys and 24 girls) aged 4 months to 16 yrs 11 months with acute hemiparesis, admitted to the Clinic of Pediatrics at St George University Hospital between 2013 and 2020. After clinical examination, a modern diagnostic and therapeutic approach was used. Results: The identified causes of acute hemiparesis were ischemic stroke (21), postictal paresis after seizure (9), hemorrhagic stroke (6), venous sinus thrombosis (5), encephalitis (3), transient ischemic attacks (TIAs) (2), posterior reversible encephalopathy syndrome (PRES) (2), hemiplegic migraine (1), demyelinating CNS disease (1), ventriculoperitoneal shunt complication (1), glutaric aciduria type 1 (1), brain tumor (1), and CNS metastasis (1). The most common manifestations associated with acute hemiparesis were impaired consciousness (27), involvement of cranial nerves – central (25) and peripheral (1) facial nerve palsy, abducens (1), ocolomotorius (1), hypoglossus (1) nerve palsy, seizures (25), raised intracranial pressure (18), speech disorders (15), signs of infection (14), headache (12), and hemibody sensory disturbances (9). In 8 children (14%), the hemiparesis was permanent, in 2 recurrent, and in 7 (12%) fatal. Conclusions: Unlike in adult patients, acute hemiparesis in children has many causes, which requires a large number of etiological studies. With a quick diagnosis and adequate treatment, recovery of function in children is more common than in adults – it is achieved in two thirds of children.

Abstract Background To report our experience with a group of patients referred for refractory CIDP who fulfilled “definite” electrodiagnostic EFNS criteria for CIDP but were found to have an alternate diagnosis. Methods Patients who were seen between 2017 and 2019 for refractory CIDP that fulfilled “definite” electrodiagnostic ENFS criteria for CIDP, but had an alternate diagnosis, were included. Patients who correctly had CIDP, anti MAG neuropathy, or MMN with conduction block, were excluded from the study. Demographics, clinical and electrophysiological characteristics, pertinent workup, final alternate diagnoses, and outcomes were collected. Results Seven patients were included: POEMS (n = 5), CANOMAD (n = 1), and neurolymphomatosis (n = 1). Most patients reported neuropathic pain and leg swelling (n = 6) or significant weight loss (n = 4). All patients had a monoclonal protein, and most patients who were tested had an elevated VEGF and CSF cyto-albuminologic dissociation. Electrophysiology showed pronounced intermediate more than distal demyelination, and axonal loss in the lower extremities. Response to steroids or IVIG varied, but some patients did respond to these treatments, especially early in the disease. Conclusion Pain, systemic symptoms, suggestive electrophysiological findings, and/or a serum monoclonal protein should raise suspicion for CIDP mimics. Initial response to steroids or IVIG, over reliance on CSF, and electrophysiology findings can all be misleading.

Introduction: Blood-induced joint damage as a hallmark of haemophilia continues to occur despite the widespread prophylaxis. Pre-cise assessment and follow-up of joint status are crucial for tailoring their treatment. Aim: To study the correlation between the bleeding phenotype, the functional joint status, and the magnetic resonance imaging score in pediatric patients with haemophilia.Materials and methods: Eighty-six joints (ankles, knees, and elbows) in patients aged 10.7±0.5 (range 4 - 20) years with severe/moderate haemophilia A, severe haemophilia B and haemophilia A with inhibitors were included in the study. The joints were assessed by Haemophilia Joint Health Score 2.1 (HJHS2.1) one month after the last hemarthrosis in a non-bleeding state. The magnetic reso-nance imaging was performed on 40 (46.5%) of the examined hemophilic joints (16 ankles, 11 knees and 13 elbows). Results: Joint bleeds were present in 37 (38.9%) of the joints with ankles being the most commonly affected. Sixty joints (69.8%) had normal HJHS2.1 score. Only the loss of flexion score differed significantly between the joints and the ankles had highest score. The cumulative number of hemarthrosis in the joint correlated moderately with hemosiderin deposition and strongly with the formation of subchondral cysts on magnetic resonance imaging. The magnetic resonance imaging scores for soft tissue and osteochondral domains correlated moderately with the cumulative number of hemarthrosis in the joint and only with the presence of pain and crepitus of mo-tion from the physical examination.Conclusions: Magnetic resonance imaging is more sensitive than the bleeding phenotype and physical examination in detecting early signs of haemophilic arthropathy.

The aerobic capacity is considered to be a prerequisite for high training and competitive performance in judo. However, it is not clear how the differences in the body composition of judokas affect their aerobic performance. The present study was aimed at comparing the body composition variables and aerobic capacity among judo players from different weight categories and examining the best method for scaling the VO2 max for differences in body mass. The subjects were 109 male and 108 female judokas 15-26 years old, grouped in three weight categories for each sex. Percentage of body fat (%BF) was predicted by skinfold equations. Fat mass, fat-free mass (FFM) and BMI were also calculated. The maximal oxygen uptake (VO2max) was measured during a graded maximal bicycle ergometer test. The correlations between VO2max, normalized by different methods, and body size variables were tested by Pearson’s productmoment correlations. The %BF and body composition variables significantly differed among weight categories and were with the highest values in the heaviest athletes. The average V̇O2max.BM-1 of the entire groups of male and female judokas were respectively 48.4±4.7 ml.kg-1.min-1 and 39.7±4.0 ml.kg-1.min-1. The lightweight classes demonstrated the highest relative to BM values of V̇O2max. When VO2max was adjusted to BM with derived allometric exponents (0.77 for males and 0.69 for females) the results for the three weight categories of male and female judokas were similar, regardless of the differences in their body composition. The interpretation of the between-weight categories differences in aerobic capacity in judokas is dependent on the method of expression of VO2 max. The VO2 max, normalized for BM or FFM, did not remove the effect of body size and still correlated with body composition variables in both sexes. The power function expression of VO2 max produced size-free variables, which did not correlate with body size in judokas.

In the article, a comparative analysis is performed regarding the accuracy parameter in determining the degree of self-similarity of fractal processes between the following methods: Variance-Time plot, Rescaled Range (R/S), Wavelet-based, Detrended Fluctuation Analysis (DFA) and Multifractal Detrended Fluctuation Analysis (MFDFA). To evaluate the methods, fractal processes based of Fractional Gaussian Noise were simulated and the dependence between the length of the simulated process and the degree of self-similarity was investigated by calculating the Hurst exponent (H > 0.5). It was found that the Wavelet-based, DFA and MFDFA methods, with a process length greater than 214 points, have a relative error of the Hurst exponent is less than 1%. A methodology for the Wavelet-based method related to determining the size of the scale and the wavelet algorithm was proposed, and it was investigated in terms of the exact determination of the Hurst exponent of two algorithms: Haar and Daubechies with different number of coefficients and different values of the scale. Based on the analysis, it was determined that the Daubechies algorithm with 10 coefficients and scale (i = 2, j = 10) has a relative error of less than 0.5%. The three most accurate methods are applied to the study of real cardiac signals of two groups of people: healthy and unhealthy (arrhythmia) subjects. The results of the statistical analysis, using the t-test, show that the proposed methods can distinguish the two studied groups and can be used for diagnostic purposes.

affected by fires is increasing. Purpose: Purpose of the study is to analyze the structure and number of irreversible losses occurring at the point of traumatic fire damage in Pleven region and comparative analysis of the country. Methods: Original retrospective survey for ten years in the Pleven district, archival-documentary and statistical methods of study were used. Data processed statistically with SPSS19. Results: The results of the study indicate the reasons for the occurrence of a fire and the occurrence of the death in case of fires in the Pleven region. Conclusions: Special attention and care by the civil service and public organizations should be addressed to the elderly and lonely living people, mostly in the villages, and their winter heating and the operation of the heaters.

Introduction: There is still conflicting information about the prevalence of EDs with female athletes. The results for different countries and subpopulations of athletes also show large variations due to various reasons including intercultural differences, eating habits and behaviors. Purpose: The aim of this first for Bulgaria study was to examine the prevalence of eating disorder attitudes and behaviors among Bulgarian female athletes and to estimate how eating disorders vary across the nature of the sport and level of proficiency. Methods: A total of 363 female athletes, aged between 12-25 years participated in the study. All participants completed an anonymous paper-based EDE-Q and provided information about their age, sports experience, participation in competitions and competitive level. The subjects were divided into groups according to the type of sport (aesthetic and non-aesthetic) and level of participation (non-competitive, low and high competitive level). Results: There were no differences between the athletes in the subgroups with respect to any of the EDE-Q subscales. On the basis of pre-established cutoff score of 4 on EDE-Q scales and the presence of pathological eating behavior we found the same prevalence rate of eating disorder with female athletes in both aesthetic sports (33.3%) and non-aesthetic sports (31.8%). Although the tendency of increasing the incidents with DE was observed, the statistical analysis showed no significant differences between the three groups with respect to the level of participation. Conclusion: This study found a relatively high prevalence of abnormal eating patterns with Bulgarian female athletes, as measured by EDE-Q. Eating disorder behavior is a prerequisite for increased risk of mental eating disorders and serious health problems.

Pontocerebellar hypoplasia (PCH) type 2 is a very rare autosomal recessive neurodegenerative disorder with prenatal onset that disrupts brain development. We present three patients (two siblings and one unrelated child) with PCH 2 linked to the most common mutation c.919G > T (p.Ala307Ser) in TSEN54 gene. The disease started soon after birth with feeding difficulties, extrapyramidal symptoms, psychomotor retardation, progressive microcephaly. Two of the patients were diagnosed with dyskinetic cerebral palsy (CP) at first. Despite the neurodegenerative character of PCH 2, the absence of regression and even some developmental progress in few patients, might erroneously lead to the incorrect diagnosis of dyskinetic CP. Megacisterna magna on brain ultrasound makes the diagnosis of PCH 2 highly probable and should prompt further imaging with MRI. MRI findings of PCH are pivotal for the diagnosis. Genetic testing for the most common mutation in TSEN54 gene should also be performed. Correct diagnosis of PCH 2 is essential not only for the prognosis of the patient, but also for prenatal diagnosis in future pregnancies. Knowledge of the clinical picture of PCH 2 will lead to correct and timely diagnosis. Advanced neuroimaging procedures and molecular genetic techniques provide valuable tools for prompt diagnosis of rare, but clinically important, neurogenetic imitators of CP.

Genome sequencing of the 5,300-year-old mummy of the Tyrolean Iceman, found in 1991 on a glacier near the border of Italy and Austria, has yielded new insights into his origin and relationship to modern European populations. A key finding of that study was an apparent recent common ancestry with individuals from Sardinia, based largely on the Y chromosome haplogroup and common autosomal SNP variation. Here, we compiled and analyzed genomic datasets from both modern and ancient Europeans, including genome sequence data from over 400 Sardinians and two ancient Thracians from Bulgaria, to investigate this result in greater detail and determine its implications for the genetic structure of Neolithic Europe. Using whole-genome sequencing data, we confirm that the Iceman is, indeed, most closely related to Sardinians. Furthermore, we show that this relationship extends to other individuals from cultural contexts associated with the spread of agriculture during the Neolithic transition, in contrast to individuals from a hunter-gatherer context. We hypothesize that this genetic affinity of ancient samples from different parts of Europe with Sardinians represents a common genetic component that was geographically widespread across Europe during the Neolithic, likely related to migrations and population expansions associated with the spread of agriculture.