Changes in the first anti-seizure medication prescribed for children and adolescents with epilepsy in a tertiary clinical center in Serbia over two decades.

OBJECTIVES: We assessed the prevalence of the use of new anti-seizure medications and valproate in the female population over two decades. MATERIALS AND METHODS: We conducted a retrospective observational cross-sectional study of medical records of children and adolescents (4 - 19 years old) with newly diagnosed epilepsy in a tertiary clinical center in Serbia from 1997 to 1999 and 2017 to 2019. RESULTS: The statistical analysis revealed significant changes in the treatment of generalized and focal seizures and all etiologies of epilepsy. Valproate use in the adolescent girl population decreased significantly from 2017 to 2019. CONCLUSION: The prescription pattern of the initial anti-seizure medication changed significantly over the two decades. The results correspond to current guidelines and recommendations.

Inner Ear Malformations in Congenital Deafness Are Not Associated with Increased Risk of Breech Presentation.

BackgroundThere is speculation that an immature vestibular system may be associated with breech presentation at delivery. Our aim was to determine whether syndromes with congenital inner ear malformations were accompanied by a higher frequency of breech presentation/malpresentations than in the general population (2%-3%). Methods: A review was conducted for published literature using PubMed/MEDLINE (1936-2016), to determine frequency of breech presentation and transverse lie in cases with congenital deafness (Michel aplasia, Wildervanck syndrome, Mondini-Alexander dysplasia, Waardenburg syndrome, CHARGE syndrome, Large vestibular aqueductal syndrome, Pendred syndrome, Oculo-aurico-vertebral spectrum, Jervel and Lange-Nielsen syndrome, Usher syndrome, and Scheibe dysplasia) and vestibular nerve aplasia. Results: Identified were total of 122 cases. The frequency of breech presentation was 1.64%, and of transverse lie 1.64%, giving a total of 3.28% malpresentations. Conclusion: The results of the study suggest that congenital malformations of the vestibular apparatus are not associated with the increased risk of breech presentation at delivery.

Bell's Palsy-Retroauricular Pain Threshold.

Background and objectives: Non-motor symptoms in the form of increased sensitivity are often associated with the onset of idiopathic Bell's palsy (IBP). The aims were to determine whether the pain threshold in the retroauricular regions (RAR) in IBP patients and the time of its occurrence is related to IBP severity. Materials and Methods: The study was conducted among 220 respondents (142 IBP patients, 78 healthy subjects (HS)). The degree of IBP was graded using the House-Brackmann and Sunnybrook Grading Scales (II-mild dysfunction, VI-total paralysis), whereas the pain thresholds were measured using the digital pressure algometer. Results: We found no difference in the degree of the pain threshold between the right and left RAR in the HS group. IBP patients belonging to groups II, III, IV, and V had lower pain thresholds in both RARs than HS and IBP patients belonging to group VI. There was no difference in the degree of pain threshold in RAR between the affected and unaffected side in IBP patients. The incidence of retroauricular pain that precedes paralysis and ceases after its occurrence in groups II and III of IBP patients is noticeably lower and the incidence of retroauricular pain that occurred only after the onset of paralysis is more frequent. Also, we found that the incidence of retroauricular pain that precedes paralysis and ceases after its occurrence in groups V and VI of IBP patients was more frequent. Conclusions: The degree of pain threshold lowering in RAR (bilaterally) is inversely related to the severity of IBP. We suggest that the occurrence of retroauricular pain before the onset of facial weakness is associated with higher severity of IBP while the occurrence after the onset is associated with lower severity of IBP.

European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME/CFS in Europe.

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation in Science and Technology (COST)-COST action 15111-from 2016 to 2020. The main goal of the Cost Action was to assess the existing knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report our findings and make recommendations for clinical diagnosis, health services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS.

Thermal imaging applications in neonatal care: a scoping review.

BACKGROUND: In neonatal care, assessment of the temperature of the neonate is essential to confirm on-going health, and as an early signal of potential pathology. However, some methods of temperature assessment involve disturbing the baby, disrupting essential sleep patterns, and interrupting maternal/infant interaction. Thermal imaging is a completely non-invasive and non-contact method of assessing emitted temperature, but it is not a standard method for neonatal thermal monitoring. To examine the potential utility of using thermal imaging in neonatal care, we conducted a comprehensive systematic scoping review of thermal imaging applications in this context. METHODS: We searched EMBASE, MEDLINE and MIDIRS. RESULTS: From 442 hits, 21 met the inclusion criteria and were included in the review. A significant number (n = 9) were published in the last 8 years. All the studies were observational studies, with 20 out of 21 undertaken in North America or Europe. Most of them had small cohorts (range 4-29 participants). The findings were analysed narratively, to establish the issues identified in the included studies. Five broad themes emerged for future examination. These were: general thermal physiology; heat loss and respiratory monitoring; identification of internal pathologies, including necrotising enterocolitis; other uses of thermal imaging; and technical concerns. The findings suggest that thermal imaging is a reliable and non-invasive method for continuous monitoring of the emitted temperature of the neonates, with potential for contributing to the assurance of wellbeing, and to the diagnosis of pathologies, including internal abnormalities. However, the introduction of thermal imaging into everyday neonatology practice has several methodological challenges, including environmental parameters, especially when infants are placed in incubators or open radiant warmers. CONCLUSION: In conclusion, although the first attempt at using thermal imaging in neonatal care started in the early-1970s, with promising results, and subsequent small cohort studies have recently reinforced this potential, there have not been any large prospective studies in this area that examine both the benefits and the barriers to its use in practice.

The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a common and severe disease with a considerable social and economic impact. So far, the etiology is not known, and neither a diagnostic marker nor licensed treatments are available yet. The EUROMENE network of European researchers and clinicians aims to promote cooperation and advance research on ME/CFS. To improve diagnosis and facilitate the analysis of clinical trials surrogate markers are urgently needed. As a first step for developing such biomarkers for clinical use a database of active biomarker research in Europe was established called the ME/CFS EUROMENE Biomarker Landscape project and the results are presented in this review. Further we suggest strategies to improve biomarker development and encourage researchers to take these into consideration for designing and reporting biomarker studies.

Social competence among well-functioning adolescents with epilepsy.

PURPOSE: The aims of the study were to measure the social competence of well-functioning adolescents with epilepsy and compare it with that of their healthy peers as well as to analyze the effects of epilepsy-related variables on the social competence. METHODS: Ninety well-functioning adolescents with epilepsy 12-19years of age were compared with healthy controls using the Achenbach Youth Self-Report Questionnaire measures of social competence. Within the group with epilepsy, the impact of duration of epilepsy, etiology, seizure frequency, seizure type, and antiepileptic drugs (AEDs) (monotherapy or polytherapy) on the above measures was also determined. RESULTS: Twenty-five (27.8%) adolescents with epilepsy obtained Total Competence T scores in the clinical range, as opposed to only two (3.3%) of the healthy adolescents. There were statistically significant differences in the Activity and Social subscales and Total Competence T score between the group with epilepsy and the control group (p<0.05). Comparing T scores for epilepsy-related variables in the group with epilepsy, we found that there were statistically significant differences in all the social competence subscales regarding the seizure control and seizure types. No significant differences were obtained for other epilepsy-related variables: duration of epilepsy, onset of epilepsy, etiology, and AEDs. CONCLUSION: Our results indicate that adolescents with epilepsy are less active in clubs, socialize less with their friends, and have a poorer school performance compared with their healthy peers. This study shows that adolescents with epilepsy are at an increased risk of having difficulties in social competence.

Breech presentation and the cornual-fundal location of the placenta.

AIM: To investigate the association of cornual-fundal location of the placenta and breech presentation at term delivery. METHODS: This study was conducted at the Department of Obstetrics and Gynecology, Novi Sad, in 2011. The inclusion criteria were delivery at ≥37 weeks of gestation, singleton gestation, and cornual-fundal location of the placenta determined by ultrasonography at ≥37 weeks of gestation when 3/4 or more of the placenta was in the cornual-fundal region. RESULTS: Out of 2750 ultrasound examinations performed, 143 showed cornual-fundal location of the placenta (frequency 5.2%). Eighty six cases had cephalic presentation (60.14%) and 57 (39.86%) had breech presentation. Of the remaining cases with non- cornual-fundal location, 2585 had cephalic presentation and 22 (0.84%) had breech presentation. The difference in the frequency of breech presentation between the cornual-fundal and non-cornual-fundal groups was significant (χ(2)=77.78, P<0.001). CONCLUSION: Cornual-fundal location of the placenta may be an important clue in resolving the etiology of a number of cases of breech presentation at term delivery.

Corrected evaluation of the breech presentation outcome based on etiology of this presentation in congenitally malformed uterus.

Background: Breech presentation (BP) results from at random filling of the intrauterine cavity, with an equal probability for a BP or cephalic presentation (CP). Each fetus in BP has its "pair" in CP randomly assumed CP. Direct comparison of BP and CP makes bias to less expressed differences between these two groups. It is therefore necessary to subtract the number of fetuses/newborns from the CP set that are identical to the number of fetuses/newborns in the BP set, with identical characteristics, and add this group to the BP set before comparing them to the rest of the CP fetuses/newborns in the matching process. Methods: The procedure encompasses nine variables in pregnancies with a congenitally malformed uterus (CMU) identified at the Department of Obstetrics (1985-2014): gestational age, birth mass, birth length, head circumference, shoulders circumference, umbilical length, placental weight, newborn mass/newborn length ratio, and newborn mass/placental mass ratio. Firstly, the probability of BP was determined and its relation to gestational age, physical characteristics, and previous presentations. Then direct comparison as well as case-control matching of the CP and BP were performed. Case-control matching was based on either a single specific variable (M1) or all combined variables (M2). Findings: 462 deliveries were identified with CMU. In 81 cases of multiparity, a fetal presentation was found to be an independent event regardless of the previous presentation, gestational age, and newborn physical characteristics. In four types of CMU with 337 deliveries (Bicornuate, Didelphys, Unicornuate, Arcuate), 9 variables with 36 instances of comparison were observed. M1 in 10 instances and M2 in 6 instances showed a statistically significant lower value of breech/random presentation compared with CP. CP have lower value in 2 instances in M1 and 1 in M2. Statistically significant differences were absent without the matching process. Interpretations: The study confirms the maximum probability for the BP is 50%. The case-control matching procedure shows that it is able to detect the difference between the breech/random presentation and CP, while the classic method of direct comparison was unable to detect any differences. The outcome of the breech/random presentation in CMU should be evaluated with the described case-control matching procedure.

The influence of continuous prenatal exposure to valproic acid on physical, nociceptive, emotional and psychomotor responses during adolescence in mice: Dose-related effects within sexes.

Clinical findings show that the use of valproic acid (VPA) during pregnancy increases the risk of birth defects and autism spectrum disorder in offspring. Although there is a consensus that monitoring of potential long-term outcomes of VPA exposure is needed, especially in undiagnosed individuals, preclinical studies addressing this issue are rare. The present study examined the effects of continuous intrauterine exposure to a wide dose range of VPA (50, 100, 200, and 400 mg/kg/day) on the physical and behavioral response in peripubertal mice as a rodent model of adolescence. Body weight and the hot plate test [on postnatal days (PND) 25 and 32], the elevated plus-maze test (on PND35), and the open field test (on PND40) served to examine physical growth, the supraspinal reflex response to a painful thermal stimulus and conditional learning, anxiety-like/risk-assessment behavior, as well as novelty-induced psychomotor activity, respectively. VPA exposure produced the following responses: (i) a negative effect on body weight, except for the dose of 100 mg/kg/day in both sexes; (ii) an increase in the percentage of animals that responded to the thermal stimulus above the defined cut-off time interval and the response latency in both sexes; (iii) dose-specific changes within sexes in behavior provoked by a novel anxiogenic environment, i.e., in females less anxiety-like/risk-assessment behavior in response to the lowest exposure dose, and in males more pronounced anxiety-like/risk-assessment behavior after exposure to the highest dose and 100 mg/kg/day; (iv) dose-specific changes within sexes in novelty-induced psychomotor activity, i.e., in females a decrease in stereotypy-like activity along with an increase in rearing, and in males a decrease in stereotypy-like activity only. These findings show that continuous intrauterine exposure to VPA produces maladaptive functioning in different behavioral domains in adolescence and that the consequences are delicate to assess as they are dose-related within sexes.

Which precocial rodent species is more suitable as the experimental model of microgravity influence on prenatal musculosketal development on international space station?

The International Space Station (ISS) has the possibility to perform experiments regarding rodent reproduction in microgravity. The musculoskeletal system at birth in precocial rodent species more resembles the human than that of altricial rodent species. For precocial rodent species with body weight ≤ 500 g (limit of ISS) determined were: adult body mass, newborn body mass, head-body length, tail length, existing variants (wild, domesticated, laboratory), single/group housing, dry food consumption/24 h, water intake/24 h, basal metabolic rate mlO2/g/h, environmental temperature, sand baths, urine output ml/24 h, fecal output g/24 h, size of fecal droplet, hair length, life span, length of oestrus cycle, duration of pregnancy, building nest, litter size, stage of musculoskeletal maturity at birth, and the duration of weaning. Characteristics were obtained by searching SCOPUS as well as the World Wide Web with key words for each of the species in English, Latin and, local language name. These characteristics were compared in order to find most appropriate species. Twelve precocial rodent species were identified. There is not enough data for Common yellow-toothed cavy, and Eastern spiny mouse. Inappropriate species were: Gundis, Dassie rat are a more demanding species for appropriate tending, litter size is small; Octodon degus requires sand baths as well as a nest during the first two weeks after delivery; muscle maturity of Spiny mouse at birth (myotubular stage), does not correspond to the human (late histochemical stage); Chinchilla requires separately housing, daily sand baths, has upper limit of weight. Possibility of keeping Southern mountain cavy as pet animal, short estrus, large litter size, absence of the need for nest and sand baths, makes this species the most promising candidates for experiments on ISS. If an experiment is planned with exposing gravid animals before term of the birth, then they might be kept together in the existing Rodent Habitat (USA). If an experiment with birth in microgravity is planned on ISS, the existing habitats do not provide conditions for such an experiment. It is necessary to develop habitats for separate keeping of pregnant animals to enable the following: 1. undisturbed delivery 2. prevent the possibility of hurting the newborns 3. ensure adequate post-partum maternal care and nursing.

Diazepam diminishes temozolomide efficacy in the treatment of U87 glioblastoma cell line.

AIMS: Many patients with glioblastoma (GBM) suffer from comorbid neurological/psychiatric disorders and, therefore, are treated with psychopharmacological agents. Diazepam (DIA) is widely adopted to treat status epilepticus, alleviate anxiety, and inhibit chemotherapy-associated delayed emesis in GBM patients. Even though temozolomide (TMZ) and DIA could be found as possible combination therapy in clinical practice, there are no reports of their combined effects in GBM. Hence, it may be of interest to investigate whether DIA enhances the antitumor efficacy of TMZ in GBM cells. METHODS: U87 human GBM was used to examine the effects of combined TMZ and DIA on cell viability, and the oxygen consumption within the cells, in order to evaluate mitochondrial bioenergetic response upon the treatment. RESULTS: The cooperative index showed the presence of antagonism between TMZ and DIA, which was confirmed on long-term observation. Moreover, the level of apoptosis after the TMZ treatment was significantly decreased when administered with DIA (p < 0.001). Concomitant use of TMZ and DIA increased the basal cell respiration rate, the oxidative phosphorylation rate, and maximal capacity of mitochondrial electron transport chain, as well as the activities of complexes I and II, vs. TMZ alone (p < 0.001). CONCLUSION: Comparing our results with data reported that DIA elicits cell cycle arrest in the G0/G1 phase and favors senescence reveals that DIA diminishes TMZ efficacy in concomitant use in the treatment of GBM. However, due to its great potency to hinder GBM proliferation and metabolism, it could be considered using DIA as maintenance therapy after TMZ cycles.

Systematic review and meta-analysis of cognitive impairment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is commonly associated with cognitive complaints. To bring out the neuropsychological symptomatology inherent to ME/CFS, we conducted a systematic review according to PRISMA and MOOSE guidelines of the literature through the analysis of 764 studies published between 1988 and 2019 by using PubMed Central website and Clarivate analytics platform. We performed a meta-analysis to delineate an idea of the neuropsychological profile inherent in ME/CFS. The clinical picture typically affects visuo-spatial immediate memory (g = - 0.55, p = 0.007), reading speed (g = - 0.82, p = 0.0001) and graphics gesture (g = - 0.59, p = 0.0001). Analysis also revealed difficulties in several processes inherent in episodic verbal memory (storage, retrieval, recognition) and visual memory (recovery) and a low efficiency in attentional abilities. Executive functions seemed to be little or not affected and instrumental functions appeared constantly preserved. With regard to the complexity and heterogeneity of the cognitive phenotype, it turns out that determining a sound clinical picture of ME/CFS cognitive profile must go through a neuropsychological examination allowing a complete evaluation integrating the notion of agreement between the choice and the number of tests and the complexity intrinsic to the pathology.

Biocompatibility of mesoporous SBA-16/hydroxyapatite nanocomposite and dentin demineralized particles on human dental pulp stem cells.

In the present work, a biomaterial (SBA-16/HA) based on the growth of hydroxyapatite (HA) particles within an organized silica structure SBA-16 (Santa Barbara Amorphous-16) was developed to evaluate its application to act as a porous microenvironment promoting attachment and viability of human dental pulp stem cells of healthy deciduous teeth (SHED). First, SHED were isolated and their phenotypes were evaluated by flow cytometry. The samples of SBA-16/HA were characterized by X-ray diffraction (XRD), small and wide angle X-ray scattering (SWAXS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) equipped with energy dispersive spectra detector (EDS). Afterward, cells were cultured in the eluates of the above-mentioned biomaterial aged for 24 hr, 7. and 14 days. Bio-Oss® and dentin particles are involved for comparison and cells are cultured in the eluates of these two materials also. Thiazolyl Blue Tetrazolium bromide assay-MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay) was used for the determination of cell viability. The results obtained by all aforementioned characterization methods of SBA-16/HA, revealed a uniform spherical mesoporous structure, an intrinsic characteristic of this material. This material displayed excellent biocompatibility on SHEDs, and even proliferative potential, indicating that SBA-16/HA could potentially serve as a suitable substrate for bone regeneration. Contrary to SBA-16/HA, dentin particles showed low cytotoxicity at all time points, compared to control and Bio-Oss®groups. Our results substantiate the idea that SBA-16/HA has a beneficial effect on SHEDs, thus paving the way toward developing new material for bone replacement.

Hallmarks of tumor-associated microglia response to experimental U87 human glioblastoma xenograft.

Glioblastoma (GBM) is one of the deadliest primary brain neoplasm, heavily infiltrated with tumor-associated microglia/macrophages (TAM), which has received a great deal of interest. Bearing in mind that the number of peripheral macrophages by the 14th day is negligible, in our study TAM were referred to as microglia. Here we evaluated histopathological characterization of TAM and kinetics of their infiltration in U87 orthotopic GBM, a commonly used model in preclinical research. To mimic different stages of GBM growth, we evaluated three-time points. Our data showed that the highest areal density of TAM was 7 days after GBM inoculation, with ability to proliferate early after initiation of GBM growth. The areal density of TAM within the tumor correlated with GBM growth and proliferation. Moreover, microglia underwent substantial morphological changes upon exposure to GBM cells. A transition from ramified morphology in peritumoral area to ameboid shape with larger soma and shortened, thick branches in the tumor core was observed. Higher areal fraction of blood vessels also correlated with the areal density of TAM. Given these pro-invasive features of microglia, this GBM model represents a good basis for further testing microglia as a target and new strategy to fight with.

Cognitive impairment and depression after acute myocardial infarction: associations with ejection fraction and demographic characteristics.

Cognitive impairment and depression are often associated with acute myocardial infarction, however, the risk factors for their occurrence after myocardial infarction are still unclear. To determine the effect of reduced ejection fraction and demographic characteristics on the occurrence of cognitive impairment and depression after myocardial infarction. In the prospective study, the final sample consisted of 82 patients. Based on the value of the ejection fraction, the patients were divided into those with a value of < 40% and those having a value of ≥ 40%. Demographic data (age, gender, education), and data on comorbidities, were collected from the patients' medical history. The instruments of studies were: Mini-mental test and Beck depression inventory. The occurrence of cognitive impairment and depression was not, to a significant degree, associated with the level of ejection fraction. In contrast, demographics have shown positive predictive effects. Among demographic characteristics, the age of the patient proved to be a significant predictor for the occurrence of cognitive impairment (p = 0.004). The probability of cognitive impairment increases 1.16 times for each year of life. Significant depression predictor was female gender (p = 0.014). The probability of depression was 3.5 times greater for female gender. Cognitive impairment after acute myocardial infarction is more common in older patients, and depression in more common in women.

Chronic Polyhydramnios: A Medical Entity Which Could Be a Model of Muscle Development in Decreased Mechanical Loading Condition.

Polyhydramnios is a condition related to an excessive accumulation of amniotic fluid in the third trimester of pregnancy and it can be acute and chronic depending on the duration. Published data suggest that during muscle development, in the stage of late histochemical differentiation decreased mechanical loading cause decreased expression of myosin heavy chain (MHC) type 1 leading to slow-to-fast transition. In the case of chronic polyhydramnios, histochemical muscle differentiation could be affected as a consequence of permanent decreased physical loading. Most affected would be muscles which are the most active i.e., spine extensor muscles and muscles of legs. Long-lasting decreased mechanical loading on muscle should cause decreased expression of MHC type 1 leading to slow-to-fast transition, decreased number of muscle fiber type I especially in extensor muscles of spine and legs. Additionally, because MHC type 1 is present in all skeletal muscles it could lead to various degrees of hypotrophy depending on constituting a percentage of MHC type 1 in affected muscles. These changes in the case of preexisting muscle disorders have the potential to deteriorate the muscle condition additionally. Given these facts, idiopathic chronic polyhydramnios is a rare opportunity to study the influence of reduced physical loading on muscle development in the human fetus. Also, it could be a medical entity to examine the influence of micro- and hypogravity conditions on the development of the fetal muscular system during the last trimester of gestation.

An Application of a Hybrid Intelligent System for Diagnosing Primary Headaches.

(1) Background: Modern medicine generates a great deal of information that stored in medical databases. Simultaneously, extracting useful knowledge and making scientific decisions for diagnosis and treatment of diseases becomes increasingly necessary. Headache disorders are the most prevalent of all the neurological conditions. Headaches have not only medical but also great socioeconomic significance. The aim of this research is to develop an intelligent system for diagnosing primary headache disorders. (2) Methods: This research applied various mathematical, statistical and artificial intelligence techniques, among which the most important are: Calinski-Harabasz index, Analytical Hierarchy Process, and Weighted Fuzzy C-means Clustering Algorithm. These methods, techniques and methodologies are used to create a hybrid intelligent system for diagnosing primary headache disorders. The proposed intelligent diagnostic system is tested with original real-world data set with different metrics. (3) Results: First at all, nine of 20 attributes - features from International Headache Society (IHS) criteria are selected, and then only five most important attributes from IHS criteria are selected. The calculation result based on the Calinski-Harabasz index value (178) for the optimal number of clusters is three, and they present three classes of headaches: (i) migraine, (ii) tension-type headaches (TTHs), and (iii) other primary headaches (OPHs). The proposed hybrid intelligent system shows the following quality metrics: Accuracy 75%; Precision 67% for migraine, 74% for TTHs, 86% for OPHs, and Average Precision 77%; Recall 86% for migraine, 73% for TTHs, 67% for OPHs, Average Recall 75%; F1 score 75% for migraine, 74% for TTHs, 75% for OPHs, and Average F1 score 75%. (4) Conclusions: The hybrid intelligent system presents qualitative and respectable experimental results. The implementation of existing diagnostics systems and the development of new diagnostics systems in medicine is necessary in order to help physicians make quality diagnosis and decide the best treatments for the patients.

Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology.

This review aimed at determining the prevalence and incidence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Europe. We conducted a primary search in Scopus, PubMed and Web of Science for publications between 1994 and 15 June 2019 (PROSPERO: CRD42017078688). Additionally, we performed a backward-(reference lists) and forward-(citations) search of the works included in this review. Grey literature was addressed by contacting all members of the European Network on ME/CFS (EUROMENE). Independent reviewers searched, screened and selected studies, extracted data and evaluated the methodological and reporting quality. For prevalence, two studies in adults and one study in adolescents were included. Prevalence ranged from 0.1% to 2.2%. Two studies also included incidence estimates. In conclusion, studies on the prevalence and incidence of ME/CFS in Europe were scarce. Our findings point to the pressing need for well-designed and statistically powered epidemiological studies. To overcome the shortcomings of the current state-of-the-art, EUROMENE recommends that future research is better conducted in the community, reviewing the clinical history of potential cases, obtaining additional objective information (when needed) and using adequate ME/CFS case definitions; namely, the Centers for Disease Control & Prevention-1994, Canadian Consensus Criteria, or Institute of Medicine criteria.