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This study aimed to evaluate the effect of biostimulants derived from Streptomyces avermitilismetabolites on entomopathogenic nematodes: Steinernema carpocapsae, Steinernema feltiae, and Heterorhabditis bacteriophora, obtained from the soil of several Miscanthus× giganteusplantations in 2020–2023. The nematodes were isolated, identified, and cultured using live insects (the greater wax moth Galleria mellonella). Three preparations containing biostimulants – Charkor, Stimpo, and Regoplant, were tested for compatibility with entomopathogenic and plant parasitic nematodes. Their effect on nematode survival was evaluated using the Petri dish test. The study showed that the effect of biostimulants on the survival of nematodes depended on the concentration of aversectin contained in the evaluated preparations. Stimpo and Regoplant had an adverse effect on plant parasitic nematodes. The highest G. mellonellamortality was observed at the higher dose of Charkor (0.4%), and the lowest at the lower dose of Regoplant (1.22%). The study showed that the virulence of the nematodes decreased after 48 hours of incubation in Regoplant and Stimpo solutions containing aversectin. The degree of interaction between nematodes depended on the nematode species, trophic preferences, and the concentration of active ingredients in the preparations. This conclusion is crucial for the selection of appropriate types of entomopathogenic nematodes and the application rate of plant parasitic nematodes in the assessment of their short- and long-term spread, persistence, and recycling in field conditions.

Coenurosis is a cystic parasitic disease affecting ruminants and other mammals worldwide. The disease is caused by Coenurus cerebralis, the larval stage of the tapeworm Taenia multiceps.Sheep and goats are frequently infected, while cases in cattle are rare. Here we describe the first recorded case of bovine coenurosis in North Macedonia. The diagnosis was based on the neurological clinical signs and the postmortem findings of a 1-year-old bull with symptoms typical for coenurosis, i.e. ataxia, circling movements, mild depression and impaired vision. Postmortem, a cyst was found in the left cerebral hemisphere and was confirmed as fertile Coenurus cerebralisby parasitological analysis. These findings suggest that coenurosis should be considered part of the differential diagnosis in cattle with neurological symptoms. This highlights the need for routine surveillance of this disease in livestock and proactive tracking of the parasite in the final hosts to enhance disease management.

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions, as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts genes overexpressed in tumors and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW motifs consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B regulates R-loops and contributes to R-loop mutagenesis in cancer.

IMPORTANCE: Patients with cancer who continue to smoke tobacco experience greater treatment-related complications, higher risk of secondary cancers, and greater mortality. Despite research to improve smoking cessation care within clinical oncology, implementation of proposed interventions within routine care remains challenging. OBJECTIVE: To identify and recommend implementation strategies for smoking cessation interventions associated with improved screening, advice-giving, and referral for tobacco users recently diagnosed with cancer, as well as shifting smoking behaviors and attitudes in this patient population. EVIDENCE REVIEW: MEDLINE, CINAHL, Embase, and PsycINFO databases, as well as Google Scholar, were searched for articles published before September 7, 2020, using terms related to cancer, smoking cessation, and implementation science. Outcomes of interest were study characteristics, implementation strategies, and outcome measures (screening, advice, referral, abstinence rates, and attitudes). The Cochrane Risk of Bias Tool for randomized and nonrandomized studies was used to assess bias. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and Synthesis Without Meta-analysis (SWiM) guideline. Implementation strategies were categorized according to Expert Recommendations for Implementing Change (ERIC) study taxonomy. A systematic analysis was conducted focusing on studies with low or moderate risk of bias due to high heterogeneity in outcome measurement. FINDINGS: In total, 6047 records were screened, yielding 43 articles (10 randomized clinical trials and 33 nonrandomized studies). Four strategies were associated with improved screening, advice-giving, and referral: (1) supporting clinicians, (2) training implementation stakeholders (including clinicians), (3) changing the infrastructure, and (4) developing stakeholder interrelationships. CONCLUSIONS AND RELEVANCE: In this systematic review, supporting clinicians by providing cessation care through a trained tobacco specialist was identified as important for achieving short-term abstinence and changing attitudes among patients with cancer. Combined with a theoretical framework and stakeholder involvement, these strategies provide the basis for successful implementation of cessation support; this systematic review serves as an illustration of the methodological application and synthesis of implementation studies and other medical conditions more generally.

Genomic epidemiology has proven to be a useful tool for investigating pandemic outbreaks and tracking pathogen spread and evolution. This study describes the circulation of SARS-CoV-2 strains in N. Macedonia during a period of one year, encompassing three waves of the COVID-19 pandemic. A certain percentage (2-3%) of positive cases were continuously selected and analyzed by whole genome sequencing (WGS) technology. Using this approach, a total of 337 SARS-CoV-2 genomes were sequenced and 26 different lineages belonging to 7 clades were detected. During the first wave of the pandemic, the most dominant lineage was B.1.1, followed by B.1.1.70, which became the most dominant in the second wave. The B.1.1.7 lineage completely overpassed all other variants in the third wave. Our study strengthens the notion that the progression of COVID-19 pandemic is associated with emergence of new SARS-CoV-2 variants with increased virulence. The measure of the impact of this viral dynamic on the spread of the pandemic should be evaluated in association with other factors that might influence the transmission.

Alström syndrome (ALMS) is an autosomal recessive disorder characterized by multiple organ involvement, including progressive cone-rod dystrophy, sensorineural hearing loss, childhood obesity, and type 2 diabetes mellitus. Pathogenic variants in the ALMS1 gene are the known cause for the occurrence of this devastating condition.

Cystic echinococcosis is a cosmopolitan zoonotic infection, commonly seen in areas where livestock and dogs are kept together. The objective of this study was to investigate the prevalence of echinococcosis in slaughtered cattle and sheep in North Macedonia and to evaluate the location and fertility/sterility rates of the cysts. A total of 302 slaughtered animals were examined with visual inspection, palpation, and incision of the internal organs in order to detect cysts. Microscopic examination was carried out to determine the presence of protoscoleces. The overall prevalence of echinococcosis in slaughtered cattle and sheep was 60%. The presence of cysts increased with age in cattle. In both cattle and sheep, the most common affected organs were the liver and lungs infected with more than one cyst. The findings showed higher fertility rate in sheep which confirmed their role as the most important intermediate host. This study shows that North Macedonia is an endemic region, and serious control strategies should be implemented, with special emphasis on safety disposal of infected organs and anthelmintic treatment of the dogs.

Leptin, as a major adipokine, positively correlates with the body’s fat, while atopy is an important feature in the development of childhood asthma. We aimed to evaluate the relationship between leptin, parameters of obesity, and atopy in children with asthma. The study included 112 children (73 boys, 39 girls, mean age 11.1±2.4). 41 were overweight, 38 had asthma and a normal body mass index (BMI), and 33 were overweight asthmatics. Serum leptin levels, BMI, waist circumference (WC), and waist to hips ratio (WHR) were measured. Skin prick test (SPT)/CAP, total serum IgE, fractional exhaled nitric oxide (FeNO), and pulmonary function tests were performed. In asthmatic children, serum leptin median level was 9.2±16.2 ng/ml, in overweight children was 30.6±21.6 ng/ml, and in overweight asthmatics was 31.1±20.3 ng/ml with a significant difference between the groups (p=0.0374), yet with a significantly lower median level in the group of children with asthma compared to the overweight children: with asthma (p=0.00001) and without asthma (p=0.00001). In the three groups of patients, BMI and WC displayed a significant positive correlation with leptin (for BMI r=0.652 vs. r=0.530 vs. r=0.563, respectively and for WC r=0.508 vs. r=0.426 vs. r=0.527, respectively). No significant correlations of leptin within atopy parameters (Eo, IgE, SPT/CAP, FeNO) in all three analyzed groups (p>0.05) was detected.

Military activities can contaminate productive land with potentially toxic substances. The most common trace metal contaminant on military bases is lead (Pb). A field experiment was begun in 2016 at Fort Riley, KS, in an area with total soil Pb concentrations ranging from 900 to 1,500 mg kg–1and near‐neutral pH. The main objectives were to test the potential of Miscanthussp. for phytostabilization of the site and to evaluate the effects of soil amendments on Miscanthusgrowth, soil–plant Pb transfer, bioaccessibility of soil Pb, and soil health. The experimental design was a randomized complete block, with five treatments and four replications. Treatments were (a) existing vegetation; (b) Miscanthusplanted in untilled soil, no amendments; (c) Miscanthusplanted in tilled soil; (d) Miscanthus planted in tilled soil amended with inorganic P (triple superphosphate applied at 5:3 Pb:P); and (e) Miscanthusplanted in tilled soil amended with organic P (Class B biosolids applied at 45 Mg ha–1). Tilling and soil amendments increased dry matter yields only in the establishment year. Total Pb uptake, plant tissue Pb concentration, and soil Pb bioaccessibility were significantly less in the Miscanthusplots amended with biosolids than the Miscanthusplots with no added P across all 3 yr. Enzyme activities, organic carbon, and microbial biomass were also greater in biosolids‐treated plots. Results show that planting‐time addition of soil amendments to Pb‐contaminated soil supported Miscanthusestablishment, stabilized and reduced bioaccessibility of soil Pb, reduced concentration and uptake of Pb by Miscanthus, and enhanced soil health parameters. Lead phytoavailability and bioaccessibility were evaluated in contaminated skeet‐range soil.Phosphate amendments were effective in reducing both Pb phytoavailability and bioaccessibility.One‐time application of biosolids helped improve Miscanthusgrowth for more than 3 yr.

The relationship between leadership style and intrinsic motivation was investigated, with the potential mediating effect of socio-demographic characteristics of respondents. The sample was consisted of 100 high school teachers from various high-schools on the territory of the city of Skopje, who completed a quantitative questionnaire. The research findings suggested that XY leadership is related to turnover intention, while intrinsic motivation is related to the socio-demographic characteristics of the teachers. Furthermore, intrinsic motivation fully mediated the relationship of job satisfaction with turnover intention and partially mediated the relationships of trust in organisation with turnover intention. The results suggested that the motivation of teachers to work can be targeted through adapting leadership styles and certain organisational characteristics and benefits provided to the employees.

Aedes albopictusis an invasive mosquito species spreading throughout Europe and its presence in North Macedonia was recorded in 2016. Following the first detection in September 2018, we conducted a two-week mosquito monitoring by ovitraps in order to determine if there were established populations of Aedes albopictusin Skopje, the capital of North Macedonia. Ninety-four Ae. albopictuseggs (0 to 18 eggs per ovitrap per week) were collected from 7 (14%) ovitraps in 3 (30%) municipalities. Thirty-eight eggs (40.4%) successfully hatched and the adult mosquitoes were identified by morphology and PCR. No other potentially invasive species were identified during the monitoring period. Ae. albopictusdistribution is expanding and poses a risk for an Aedes-borne disease transmission in North Macedonia. The available data highlight the need for a regular monitoring for tiger mosquitoes to plan adequate control measures.

The impact of plant growth regulators (PGRs) “Stimpo” and “Regoplant” on Miscanthus x giganteus(Mxg) biomass parameters was investigated when the plant was grown in military soils with different properties from Dolyna, Ukraine and Hradcany, Czech Republic. The results showed that PGRs positively influenced the biomass parameters when the plant was grown in soil in Dolyna with good agricultural characteristics, the influence of “Regoplant” was higher and the best results were obtained with combined treatment: application to rhizomes before planting and spraying on the biomass during vegetation. Using of PGRs did not improve the biomass parameters when the plant was grown in poor soil in Hradcany. In parallel the peculiarities of the metals uptake process were studied for the following metals: chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), strontium (Sr) and lead (Pb). The uptake behavior of the monitored elements differed based on the soil quality. According to the bioconcentration factor uptake of the abiogenic elements, Cr and Pb, was dominant in the plant roots in both soils, whereas Ni was not detected in any plant tissues. The behavior of biogenic elements (Mn, Cu, Zn) and their analogs (Sr) was different. Those elements were more intensively taken up in shoot tissues in low-nutrient sandy Hradcany soils, while they were mainly taken up in plant roots in fertile Dolyna soils. The unusual behavior of biogenic elements in the low-nutrient soils may be explained by the effect of stress. However, more research is needed focused mainly on soil properties and nutrient availability in order to confirm or disprove this hypothesis and to explore the cause of the stress. The summarized results here show that soil properties influenced Mxgbiomass parameters, affected the uptake behavior of metals significantly and tested PGRs cannot be utilized universally in the production of Mxgin the poor military soils.

The aim of this research was to assess the effect of soil contamination with titanium (Ti) and iron (Fe) at military sites in Ukraine using the avoidance and reproduction tests with Folsomia candida(springtail). The soil used for the tests was sampled in 2017 from Dolyna, Ivano-Frankivsk region, Ukraine from two plots, namely a contaminated and a control site. The sample site is a former military site previously used for tank training. At the control site mainly the concentrations of Ti and Fe were exceeded. The control soil was free from contamination. The avoidance test and reproduction test were conducted with the use of springtail species F. candida. The following nine levels of contamination with heavy metals were established: 1%, 1.5%, 5%, 10%, 15%, 25%, 50%, 75% and 100%. The duration of the avoidance test was 7 days, and that of the reproduction test was 28 days. Overall, the results show that the avoidance and reproduction tests with collembolans have the potential to be used as screening tools in an ecological risk assessment of heavy metals. In the avoidance test, the concentrations from 1.5 to 100% significantly decreased the number of F. candidain the contamination site in comparison to the control site. At the same time, avoidance was not observed in the first concentration (1%). According to the reproduction test, the negative effect on the number of F. candidajuveniles was observed beginning at the 10% dose. The half maximal effective concentration (EC50) for the avoidance test was 50.12%, while that for the reproduction test was 22.39%. The contamination with heavy metals at the military areas indicated the short- and long-term toxicity risk on the springtail F. candida.

The most prevalent "rare" disease worldwide, cystic fibrosis (CF), is an autosomal recessive multisystem disease, caused by mutations in the CFTRgene. The knowledge of CFTRmutations present in certain population is important for designing a simple, fast and cost-effective genetic testing approach, also for better management of CF patients, including the administration of novel targeted therapies. Here, we present genetic results of 158 unrelated CF patients from the National CF Registry of the Republic of North Macedonia. Initially, patients were screened for the 11 most common CF mutations. Additional CF mutations and large deletions/duplications in the CFTRgene were analyzed using commercial kits. If the genotype was undetermined, all CFTRexons were analyzed using Sanger DNA sequencing or next generation sequencing (NGS) (since 2014). The most common CF mutation, c.l521_ 1523del (legacy name F508del), was found with an overall incidence of 75.9%. Additionally, 26 other pathogenic variants and three large deletions were identified in the CFTRgene as a genetic cause of CF. Two of these, c.1070 C>T (p.Ala357Val) and c.2779_2788dup CTTGCTATGG (p.Gly930AlafsTer48), were novel. According to the distribution and prevalence of the pathogenic variants detected in our patients, a fast and cost-effective method, based on a single base extension was designed as a first-line CF genetic test with a 90.0% detection rate within our population. Furthermore, the knowledge of CFTRmutation classes in our CF patients represents the first step toward personalized therapy for CF in our country.

Background: RNA editing has been described as promoting genetic heterogeneity, leading to the development of multiple disorders, including cancer. The cytosine deaminase APOBEC3B is implicated in tumor evolution through DNA mutation, but whether it also functions as an RNA editing enzyme has not been studied. Results: Here, we engineer a novel doxycycline-inducible mouse model of human APOBEC3B-overexpression to understand the impact of this enzyme in tissue homeostasis and address a potential role in C-to-U RNA editing. Elevated and sustained levels of APOBEC3B lead to rapid alteration of cellular fitness, major organ dysfunction, and ultimately lethality in mice. Importantly, RNA-sequencing of mouse tissues expressing high levels of APOBEC3B identifies frequent UCC-to-UUC RNA editing events that are not evident in the corresponding genomic DNA. Conclusions: This work identifies, for the first time, a new deaminase-dependent function for APOBEC3B in RNA editing and presents a preclinical tool to help understand the emerging role of APOBEC3B as a driver of carcinogenesis.

Peculiarities of metals uptake by the biofuel crop Miscanthus x giganteuswere explored during plant growth at soil from the military site (Sliač, Slovakia). The experiment was carried out in greenhouse during two vegetation seasons. Research soil was predominantly elevated in Fe and Ti, while other metals (As, Cu, Mn, Sr, Zn and Zr) were presented at order of magnitude lower concentrations. No inhibition of plant growth was observed. The calculated Bioconcentration Factor showed that levels of metals’ accumulation by plant roots, stems and leaves were independent of metals’ concentrations in the soil. The accumulation of metals by stems and leaves was much lower than by roots. As, Zr, Ti were almost not accumulated by stems and leaves during both seasons; accumulation of Cu, Fe, Mn, Zn and Sr was not essential which confirmed that biomass of M. x giganteusmight be processed for the energy purpose.

A six-month-old Pomeranian male dog was referred due to a month long history of unformed, soft faeces and mild weight loss. Stool analyses by direct faecal smear, Zinc sulphate flotation and the Baermann concentration method revealed an infection with Strongyloides stercoralis. The dog was initially treated once with a combination drug of praziquantel, pyrantel and febantel (½ Drontal®Plus Tablets for puppies and small dogs; Bayer; i.e. 31.5 mg/kg bodyweight of febantel ). The treatment was repeated after 12 days with the same dosage for 3 consecutive days. The stool analyses performed 14 days and 3 months after the second treatment were negative for S. stercoralislarvae. The results suggest that a repeated treatment with Drontal®Plus Tablets is effective against S. stercoralisin dogs and has no adverse effects.

Ehrlichia canis, the etiologic agent of canine monocytic ehrlichiosis (CME), is mainly transmitted by the brown dog tick Rhipicephalus sanguineus. Clinical signs of the disease can be various, depending on the stage of the disease. Typical changes in hematological and blood biochemical parameters are: severe thrombocytopenia, mild to marked non regenerative anaemia and hypoalbuminemia. In order to present the effects of the treatment protocol on several hematological and biochemistry parameters, 34 Ehrlichia canispositive dogs were compared before and after treatment with doxycycline 10mg/kg/day, in duration of four weeks. Besides the clinical sings and laboratory findings, diagnosis was confirmed by antibody tests (Bionote, Korea, AGROLABO S.p.A., Italy). The most common clinical sings were depression, lethargy, pyrexia, vomiting and anorexia. Hematological analyses were performed on the automatic hematology analyzer Exigo EosVet (Sweden), while biochemistry analyses (alanine aminotransferase, aspartate aminotransferase, urea, creatinine, albumin, total protein, globulin and alkaline phosphatase) were performed using the automatic analyzer ChemWell 2910 (Awareness Technology, INC, USA). Statistically significant difference (p<0.05) in hematology changes was present regarding the red blood cells count, platelet count, hematocrit and hemoglobin before and after treatment. Hypoalbuminaemia (Mean 19.21 ±4.96 g/l) was the only serum biochemistry parameter with significant change before and after treatment, as well. Treatment with doxycycline in patients with E.canisresulted in significant increase of hematology parameters (red blood cells, hemoglobin, haematocrit and platelets), as well as albumins in serum.

In view of the current availability and variety of measured data, there is an increasing demand for powerful signal processing tools that can cope successfully with the associated problems that often arise when data are being analysed. In practice many of the data-generating systems are not only time-variable, but also influenced by neighbouring systems and subject to random fluctuations (noise) from their environments. To encompass problems of this kind, we present a tutorial about the dynamical Bayesian inference of time-evolving coupled systems in the presence of noise. It includes the necessary theoretical description and the algorithms for its implementation. For general programming purposes, a pseudocode description is also given. Examples based on coupled phase and limit-cycle oscillators illustrate the salient features of phase dynamics inference. State domain inference is illustrated with an example of coupled chaotic oscillators. The applicability of the latter example to secure communications based on the modulation of coupling functions is outlined. MatLab codes for implementation of the method, as well as for the explicit examples, accompany the tutorial.

Hearing impairment is the most common sensory disorder, which occurs in 1 of 1000 newborns. It is caused by heterogeneous conditions with more than a half due to genetic etiology. Although hundreds of genes are implicated in hearing process and have been found to be associated with nonsyndromic hearing loss, pathogenic variants in GJB2gene have been considered as the main cause of deafness among nonsyndromic hearing loss (NSHL) population worldwide. Pathogenic variants in MT-RNR1or mtDNA12SrRNAgene were also implicated predominantly in postlingual progresive deafness.

Cytochrome P450 2D6(CYP2D6) is an enzyme of great importance for the metabolism of clinically used drugs. More than 100 variants of the CYP2D6gene have been identified so far. The aim of this study was to investigate the allele distribution of CYP2D6gene variants in 100 individuals of each of the Macedonian, Albanian and Romany population, by genotyping using long range polymerase chain reaction (PCR) and a multiplex single base extension method. The most frequent variants and almost equally distributed in the three groups were the fully functional alleles *1and *2. The most common non functional allele in all groups was *4that was found in 22.5% of the Albanians. The most common allele with decreased activity was *41which was found in 23.0% of the Romany ethnic group, in 11.0% of the Macedonians and in 10.5% of the Albanians. Seven percent of the Albanians, 6.0% of the Romani and 4.0% of the Macedonians were poor metabolizers, while 5.0% of the Macedonians, 1.0% of Albanians and 1.0% of the Romanies were ultrarapid metabolizers. We concluded that the CYP2D6gene locus is highly heterogeneous in these groups and that the prevalence of the CYP2D6allele variants and genotypes in the Republic of Macedonia is in accordance with that of other European populations.

The rules as we know today in modern societies have their base in the Magna Carta from 1215. In that time people declared that the rights of the king and nobles must be limited and that was the first step toward as we know today “democracy”. The rights incorporated in the Magna Carta defined the limits what a state can do and also set boundaries in order to achieve equality between the state and the individual.

Leishmaniosis caused by Leishmania infantum is vector-born severe enzootic disease in dogs. It includes a wide spectrum of clinical symptoms, but the most characteristic are alterations in the hematopoetic system and renal failure. Also, infected animals could be asymptomatic, so the manifestation of L. infantum infection depends on many factors, including host’s immunological status. The aim of this survey was to find parameters related with hematopoetic and renal failure (hematology, biochemical parameters - urea, creatinine, serum proteins) in symptomatic and asymptomatic dogs seropositive for canine leishmaniosis. Within the hematological parameters, we found significant differences between symptomatic and asymptomatic dogs in the erythrogram and platelet count, but not in the leukogram. Significant differences between the two groups were found also for urea, creatinine, serum albumin and globulin, but not in serum total protein and A/G ratio. These findings indicate individual variability of the host’s response to infection with L. infantum.

The Balkan Journal of Medical Genetics (BJMG) is an international, open access journal that publishes scientific papers covering different aspects of medical genetics. It is published by the Macedonian Academy of Sciences and Arts twice a year in both printed and electronic versions. BJMG is covered by many abstracting and indexing databases, including PubMed Central and Thomson Reuters.

Recurrent aphthous stomatitis (RAS) is a quite frequent, painful, ulcerative disease that affects the lining of the oral cavity and has an unknown etiology. The aim of this article is to examine the impact of the medication proaftol on epithelization speed and severity of pain in patients with RAS. In this randomized, double-blind, placebo-controlled study respondents were divided into two groups where one group was treated with proaftol spray and the other with a placebo. Aphthae considered for treatment had a diameter of 5-6 mm. The participants were given instruction on the use of the spray, two sprayings on the place of the aphtae 3-4 times a day. We examined two parameters in the symptomatology of RAS-lesion size (mm) and pain intensity (noted on four subjective levels: 0-no pain, 1-discomfort, 2-moderate pain, 3-severe pain). These parameters were noted on the baseline, the third, the fifth and the eighth days of examination.

Introduction. In order to improve asthma control, in the last decades an emphasis has been put on the assessment of quality of life (QL). The aim of the study was to assess the role of the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) in order to assess the QL as a marker of clinical stability in asthmatic children.

Zur arthroskopischen suprapektoralen Bizepstenodese mit intraossärer Sehnenrefixation ist in der Literatur wenig beschrieben. Ziel war die Analyse der klinischen Ergebnisse basierend auf Scores und Kraftmessung in Relation zur Gegenseite. Hypothetisiert wurde eine Verbesserung von Ellenbogenflexionskraft und klinischen Scores auf das Niveau der gesunden Gegenseite sowie die Verhinderung von „Popeye-sign“-Deformitäten des Oberarms. Die Tenodese der langen Bizepssehne (LBS) erfolgte nach arthroskopischer Sehnenarmierung mit der 6,25 mm Bio-SwiveLock®-Schraube im Sulkuseingang. Von n= 27 konsekutiv behandelten Patienten, die bei isolierter LBS-Läsion mit dieser Technik operiert wurden, sind insgesamt n= 17 Patienten eingeschlossen worden. Präoperativ sowie 3, 6 und 12 Monate postoperativ wurden klinische Scores erhoben, eine Messung des Oberarmumfangs und der Ellenbogenflexionskraft durchgeführt und mit den Werten der gesunden Gegenseite verglichen. Es zeigte sich ein signifikanter Anstieg der Scores und eine signifikante Verbesserung der Kraft 6–12 Monate nach der Operation ohne Unterschied zur Gegenseite. Die arthroskopische suprapektorale intraossäre LBS-Tenodese resultiert in einem signifikanten Anstieg der Scores und der Ellenbogenflexionskraft ohne signifikanten Unterschied zur Gegenseite. Die Ausbildung einer „Popeye-sign“-Deformität kann nicht immer verhindert werden. A lack of clinical data regarding suprapectoral arthroscopic tenodesis of the long head of the biceps tendon (LHB) is evident. This study was performed to analyze the clinical results of this technique based on scores and force measurements. The affected arm was evaluated over time and compared to the ipsilateral arm. It was hypothesized that this would result in 1) improved elbow flexion force and clinical scores up to the level of the healthy ipsilateral side and 2) avoidance of a Popeye sign deformity of the upper arm. Tenodesis of the LHB was performed by arthroscopic tendon fixation using a 6.25 mm Bio-SwiveLock screw at the sulcus entrance. Out of 27 consecutive patients who were treated by this technique for isolated LHB lesions, a total of 17 patients were included in this study. Clinical scores, force and upper arm circumference measurements were performed before surgery and 3, 6 and 12 months after the intervention. A significant improvement in clinical scores and force was found 6–12 months after surgery. Arthroscopic suprapectoral intraosseous LHB tenodesis results in a significant improvement of clinical scores and elbow flexion force with no significant differences compared to the healthy ipsilateral side within 6–12 months. A Popeye sign deformity of the biceps muscle cannot be avoided in all cases.

In order to assess outcome and possible predictors of early good results, a prospective study on 22 patients who were treated with save surgical hip dislocation for symptomatic isolated cam-type femoroacetabular impingement (FAI) was performed. After a follow-up of 6 and 12 months, standard clinical and radiographic parameters were recorded. A statistically significant improvement of the clinical status according to the Harris hip score could be assessed at six months (p-value = 0.003) and 12 months (p-value = 0.001) post-surgery. By comparing standard clinical and radiographic preoperative parameters with various follow-up outcomes, we revealed no specific parameter with predictive value. These findings are important for centers that have just started to use this surgical technique and are still identifying their learning curve.

In order to evaluate whether arterial hypertension (AH) affects skin microcirculation, 46 newly diagnosed, never-treated, hypertensive patients and 20 healthy normotensive controls underwent a forearm skin postocclusive reactive hyperaemia (PORH) test, using laser-Doppler flowmetry (LDF). Their resting skin blood flow oscillations (SBFOs) were also investigated using wavelet spectral analyses of skin LDF tracings within six frequency subintervals in the 0.005–2Hz spectral range. To evaluate whether antihypertensive treatment affects skin microcirculation, the same measurements were repeated in 22 of the recruited hypertensive patients after 8±2 weeks of antihypertensive treatment.

GJB2 Mutations in Non Syndromic Hearing Loss in the Republic of MacedoniaHearing impairment is a common sensori-neural disorder with the incidence of profound deafness in one per 1,000 births. Non syndromic recessive deafness (NSHL), accounts for approximately 80% of cases of hereditary deafness. It is extremely heterogeneous genetically with over 130 gene loci. Mutations in the GJB2and GJB6genes for DFNB1 locus (13q12) are responsible for about half of all cases of autosomal recessive prelingual hearing loss.We determined the prevalence and mutations in the GJB2gene, and the presence of delD13S1830 in the GJB6gene in DNA samples from 33 unrelated Macedonian families with recesive NSHL and 200 normal hearing individuals using single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing and specific polymerase chain reaction (PCR).We found mutations in the GJB2gene in 12 patients, but no delD13S1830 in the GJB6gene. In 22 mutated chromosomes, 15 (68.2%) had the 35delG mutation, four (6.1%) W24X, two (3.0%) V37I and one (1.5%) R127H.Because of the high mutation rate (36.4%) in the GJB2gene in NSHL patients, testing should be performed in all cases with prelingual deafness.

There is growing evidence in favor of the temporal-coding hypothesis that temporal correlation of neuronal discharges may serve to bind distributed neuronal activity into unique representations and, in particular, that θ(3.5–7.5Hz) and δ(0.5<3.5Hz) oscillations facilitate information coding. The θ- and δ-rhythms are shown to be involved in various sleep stages, and during anesthesia, they undergo changes with the depth of anesthesia. We introduce a thalamocortical model of interacting neuronal ensembles to describe phase relationships between θ- and δ-oscillations, especially during deep and light anesthesia. Asymmetric and long-range interactions among the thalamocortical neuronal oscillators are taken into account. The model results are compared with experimental observations. The δ- and θ-activities are found to be separately generated and are governed by the thalamus and cortex, respectively. Changes in the degree of intraensemble and interensemble synchrony imply that the neuronal ensembles inhibit information coding during deep anesthesia and facilitate it during light anesthesia.

Molecular Characterization of Hemophilia a in Southeast BulgariaThe results of molecular characterization of Hemophilia A in 50 patients from Southeast Bulgaria are presented. Southern blot analysis for the detection of inversions in intron 22, and polymerase chain reaction (PCR) followed by single strand conformation polymorphism (SSCP) or de-naturing gradient gel electrophoresis (DGGE) for screening of the coding sequences of the Factor VIII (FVIII) gene were used. A molecular defect was found in 35 (70%), the most frequent being an inversion in intron 22, found in 19 (38%) patients; an intron 1 inversion was not detected. In one severely affected patient, an Alu insert was found, which disrupted exon 14 at codon 1224. Nucleotide substitutions were found in 15 (30%) patients, the most frequent being an Arg531?Cys missense mutation in exon 11. The same nonsense mutation (codon -5, CGA>TGA) was found in two patients with a severe phenotype. Seven missense mutations (Asn90?Thr, Arg 372?His, Glu456?Val, Tyr473?His, Arg1689? Cys, Arg2159?Cys and Arg2163?His) were detected in isolated families. Two of these (Asn90?Thr and Glu456? Val) are being reported for the first time.

Abstract: The skin of diabetic subjects presents abnormalities in capillary blood flow and its regulation, often leading to the generation of plantar ulcers. In order to gain insight into this pathology for type 1 diabetic patients, Lyapunov exponents (LEs) of signals reflecting microvascular perfusion—laser Doppler flowmetry (LDF) signals—are calculated. The algorithm to compute LEs is first validated on simulated data and LDF surrogates. Then, LDF signals recorded at rest and during the application of local and progressive pressure of 11.1 Pa/s are processed. The exponents appear in pairs and are different for healthy and type 1 diabetic subjects at rest; P = 0.0556 for the 7th, 8th, and 9th LEs. Furthermore, progressive pressure has also a distinct effect on LEs. The difference is more pronounced for diabetic patients, for whom P = 0.0625 for the four LEs of highest absolute value. Because these differences arise from abnormalities in microvascular blood flow, they may help to explain the high prevalence of type 1 diabetic patients developing foot ulcers.

The effect of low-intensity He–Ne laser light (λ = 632.8 nm) on the rheological properties of whole human blood was studied using light-scattering techniques. Changes were detected in the average size of erythrocyte aggregates in blood following exposure to low intensity laser light under both in vitro and in vivo conditions. A theoretical model based on heat transfer theory qualitatively describes the experimental results.

Using an information-theoretic approach, causality between the systolic amplitude in blood pressure and the frequency of the heart beat was analyzed. Blood pressure and ECG were noninvasively recorded in young, healthy subjects. Three successive measurements were performed: during spontaneous breathing and during paced respiration—at frequencies both higher and lower than that of spontaneous respiration. We demonstrate that the amplitude and frequency of the cardiac rhythm are synchronized for most of the time. The synchronization is stronger during paced respiration at a frequency lower than that of spontaneous breathing. Episodes where the cardiac frequency was driven by the systolic pressure were also detected during slow, paced respiration.

Iontophoresis currents are used in the transcutaneous delivery of vasoactive substances for noninvasive assessment of skin vascular properties. The blood flow rate can be recorded by laser Doppler flowmetry (LDF), its average value and the amplitudes of its oscillatory components being used to evaluate the effect of the drugs. Because non-drug-specific, current-induced, vasodilation could confound the interpretation of the response, we have investigated the effect of currents of both polarities on the spectral components of the LDF signal in the absence of vasoactive substances. It was recorded for healthy volunteers with both high conductance (5 mol/l NaCl) and low conductance (deionized water) electrolytes. The oscillatory components were analysed by wavelet transform within 0.0095–1.6 Hz, divided into five sub-intervals. Only cathodal iontophoresis with deionized water increased the oscillatory energy and amplitude. It did so at all frequencies, but none of the sub-intervals associated with vasodilation (0.0095–0.145 Hz) was selectively affected compared to the others.

The technique of wavelet phase coherence analysis is introduced and used to explore relationships between oscillations on blood flow and temperature in the skin of 10 healthy subjects. Their skin temperature and blood flow were continuously recorded: under basal conditions for 30 min; during local cooling of the skin with an ice-pack for 20 min: and 30 min thereafter. The group mean basal skin temperature of 33.4°C was decreased to 29.2°C during the cooling period, and had recovered to 32.1°C by the end of the recording. The wavelet transform was used to obtain the time–frequency content of the two signals, and their coherence. It is shown that cooling increases coherence to a statistically significant extent in two frequency intervals, around 0.007 and 0.1 Hz, suggesting that these oscillatory components are involved in the regulation of skin temperature when cold is applied as a stress.

A prototype of a diagnostic system for quality end-tests of vacuum cleaner motors is presented. The core of the system are four modules for features extraction based on vibration analysis, sound analysis, analysis of commutation and check of parity relations respectively. The symptoms resulting there from are processed by a reasoning module relying on the Transferable Belief Model (TBM). The result of such a comprehensive diagnostic procedure is detection of faulty motors and localisation of tentative fault origins along with accompanying belief measures. Attributes of the system performance and an excerpt from results obtained in an experimental study over a series of motors are provided.

Based on physiological knowledge, and on an analysis of signals related to its dynamics, we propose a model of the cardiovascular system. It consists of coupled oscillators. Each of them describes one of the subsystems involved in the regulation of one passage of blood through the circulatory system. The flow of blood through the system of closed tubes-the blood vessels-is described by wave equations.

A mathematical model of the cardiovascular system is simulated numerically. The basic unit in the model is an oscillator that possesses a structural stability and robustness motivated by physiological understanding and by the analysis of measured time series. Oscillators with linear couplings are found to reproduce the main characteristic features of the experimentally obtained spectra. To explain the variability of cardiac and respiratory frequencies, however, it is essential to take into account the rest of the system, i.e. to consider the effect of noise. It is found that the addition of noise also results in epochs of synchronization, as observed experimentally. Preliminary analysis suggests that there is a mixture of linear and parametric couplings, but that the linear coupling seems to dominate.

The purpose of the present study was to compare the effects of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilators on the oscillatory components of the cutaneous blood perfusion signals in humans. The unstimulated basal blood perfusion and the blood perfusion during iontophoretically delivered ACh and SNP were measured using laser Doppler flowmetry (LDF). The wavelet transform was calculated before spectral analysis of the measured signals. In the frequency interval from 0.0095 to 1.6 Hz the LDF signal consists of oscillations with five different characteristic frequencies. In addition to the cardiac (1 Hz) and respiratory (0.3 Hz) rhythms, three other oscillations in the regions around 0.1, 0.04, and 0.01 Hz were detected. The oscillations with the different frequencies were observed in unstimulated blood flow and also during stimulation with ACh and SNP. Compared to the unstimulated blood flow, both ACh and SNP increased the mean amplitude of the total spectrum (P< 0.005 for both substances). The only significant difference between the effects of ACh and SNP was observed in the amplitude of oscillations with the frequency of around 0.01 Hz. ACh increased the absolute amplitude of this frequency to a greater extent than SNP in athletes (P= 0.03), whereas only a trend was observed in controls (P= 0.2). The relative amplitude, defined as the ratio between the absolute amplitude of a particular frequency interval and the mean amplitude of the total spectrum, was also higher for ACh compared to SNP both in controls (P= 0.008) and in athletes (P= 0.004), only for oscillations with the frequency of around 0.01 Hz. We conclude that ACh selectively influences the oscillatory component of around 0.01 Hz in the cutaneous blood perfusion signal to a greater extent than SNP. This finding indicates that endothelium-mediated vasodilatation is manifested as oscillations with a repetition time of approximately 1 min. The mechanisms for the endothelial dependency of this frequency remain to be elucidated. Our data indicate that spectral analysis based on wavelet transform of the cutaneous perfusion signal can be used clinically to investigate endothelial function. The described noninvasive method might be used to evaluate endothelial function for research, for diagnostic purposes, and maybe also to assess effects of therapy in cardiovascular diseases.

In order to gain an insight into the dynamics of the cardiovascular system throughout which the blood circulates, the signals measured from peripheral blood flow in humans were analyzed by calculating the Lyapunov exponents. Over a wide range of algorithm parameters, paired values of both the global and the local Lyapunov exponents were obtained, and at least one exponent equaled zero within the calculation error. This may be an indication of the deterministic nature and finite number of degrees of freedom of the cardiovascular system governing the blood-flow dynamics on a time scale of minutes. A difference was observed in the Lyapunov dimension of controls and athletes.

Abstract: Subjects with spinal cord injury are often distressed by pressure sores, which usually appear after prolonged pressure (wheelchair, bed) across the soft tissue which has already lost sensibility and has diminished microcirculation. The healing ability and its dynamics depend on the state of the subject's overall health. Consequently, evaluation of a particular treatment requires careful consideration of as many as possible of the parameters relevant to healing and an adequate criterion for assessing the state of the pressure sore. Bearing in mind these two circumstances, the results of a multicentre clinical study are analysed. The aim of the study was to test two hypotheses: first that healing is faster when sores are also treated by electric currents (ECs) (in addition to conventional treatment); and secondly that there exist differences in the efficiency of the treatment if direct or low-frequency pulsed currents (FES parameters) are applied. The data analysed show that pressure sores are likely to heal twice as fast when treated with low-frequency pulsed currents. EC seems to improve the healing rate in cases where the natural healing mechanisms of the body are not sufficient (chronic wounds, older subjects).

The paper presents reconstruction of cardiovascular dynamics based on analysis of signals measured from various functions of the cardiovascular system on different sites of the human body. All signals comprise the same characteristic peaks in their frequency spectra. The time variations of these peaks are illustrated using wavelet transform. To further reveal the dynamic properties of the cardiovascular system the signals are analysed in the phase space by calculating the correlation integral and Lyapunov exponents. The correlation integrals of measured signals differ from those of their surrogates, and the Lyapunov exponents appear in pairs. The obtained results suggest the complex and deterministic nature of the system that governs cardiovascular dynamics. A model of coupled oscillators is proposed to describe the dynamics of the cardiovascular system.