Investigations of solid tumors have shown that a very specific characterization of aberrant tissues can best be performed using a combination of cytologic, cytogenetic and molecular-cytogenetic methods. Thus, cytological analyses may serve to examine various features of tumors cultivated in vitro, e.g. growth peculiarities, cell morphology, specific details of cell division and mitotic rates, and anomalies of the spindle apparatus. Besides, chromosomal diagnostics characterizing non-specific aberrations focuses on the pathological karyotype and its evolution and heterogeneity, as well as on the development of secondary chromosomal aberrations. In the field of molecular-cytogenetic diagnostics we emphasize particularly the combination of metaphase and interphase analyses and the investigation of specific structural aberrations by fluorescence in situ hybridization (FISH). In contrast to the method of comparative genomic hybridization (CGH), the spectrum of applications for both methods is discussed. The findings described in this paper were obtained primarily from the analysis of 68 tumors of the urogenital tract (20 kidney tumors, 33 bladder tumors, 15 testis tumors).
PURPOSE:Presentation of four patients with bilateral peripheral facial nerve palsy as a clinical manifestation of neuroborreliosis in children--diagnostic, treatment and prognosis.MATERIAL AND METHODS:In 2002-2004 in The Chair and Department of Developmental Neurology, 24 children from the Wielkopolska region were admitted with diagnosis of borreliosis. Among all the children with borreliosis, confirmed by serologic examination, 4 (16.7%) demonstrated bilateral peripheral facial palsy (PFP). We investigated the presence of IgM class and IgG class specific antibodies in the sera and cerebrospinal fluid (CSF) of 4 patients with bilateral PFP. (Detected by immunoenzymatic methods--ELISA.)RESULTS:Before the occurrence of PFP all the children manifested unspecified systemic symptoms such as headaches, muscle and articulation pains, weakness and in two cases a mood depression. At first all patients demonstrated elevated IgM antibodies and proper levels of IgG antibodies. Control tests administered within 2-14 months later reduction of antibodies was indicated. Two patients demonstrated significant pleocytosis in CSF test, (without the meningeal symptoms). All children were treated with physiotherapeutic procedures and were administered antibiotic intravenously.CONCLUSIONS:PFP is one of the most frequent neurological symptoms of borreliosis in children. In case of acute PFP and especially the bilateral form of PFP, neuroborreliosis is the most probable diagnosis. All children reported PFP at one side first and after several weeks the paresis of the facial nerve on the opposite side usually appeared. The clinical state of children started to improve after the introduction of physiotherapy and this process usually lasted several months.
PURPOSE:Food allergy has been demonstrated to play an important role in the pathogenesis of atopic eczema dermatitis syndrome (AEDS), affecting often atopic infants and young children. The most commonly offending foods are cow's milk, hen's egg, wheat and soy; implicating immediate (IgE-mediated) and late-phase (T-cells) immunological reactions in the pathogenesis of skin lesions. The diagnostic work-up of suspected immediate food reactions includes skin prick tests (SPT) and the measurement of food-specific antibodies (sIgE). The methodology of atopy patch test (APT) has been reported as a diagnostic tool with high predictive capacity for late-phase clinical reactions in children with atopic dermatitis. Although APT has been introduced into the diagnostic procedure for food allergy, its diagnostic accuracy remains still controversial; especially in older children. The aim of study was to evaluate the diagnostic accuracy of the atopy patch test in the detection of food allergy in correlation with SPT, sIgE and positive oral food challenge to milk, in children suffering from AEDS and to assess the sensitivity and specificity of this method in dependence on the age of investigated children. MATERIAL AND METHODS:34 children (25 boys, 9 girls) aged 5 months-16 years with suspicion of milk-related AEDS were investigated. These patients were subdivided into 2 age groups: group A--20 children (<3 years), group B--14 children (>3 years). The diagnostic procedures as skin-prick tests and atopy patch test were performed. The specific IgE to cow's milk allergens were also measured. The open and blind diagnostic oral food challenge were performed to verify the results of tests. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive value of APT were calculated in both age groups. RESULTS:A positive challenge response to milk was found in 65.0% of investigated children in group A and in 35.7% in group B. No statistical differences in the prevalence of immediate (p<0.1905) and delayed-type (p<0.409) reactions has been found between age groups. Positive APT to milk were noticed in 55.0% of patients in group A and in 35.7% of children from group B, that has been in correlation with positive delayed-type reactions in oral food challenge in 72.7% and 80.0% in corresponding age groups. Polysensitization to other food allergens confirmed by SPT and/or sIgE was detected in 35.0% of patients younger than 3 years of age and in 50.0% of older children. The prevalence of positive APT to other foods (soy, rice, maize, cereals) was significantly higher (p<0.0073) in the polysensitized children from group A. Sensitivity of SPT/sIgE in children with immediate-type reactions to milk was 100%, specificity 94%. Sensitivity of APT to cow's milk in children with late-phase reactions was 80% in both age groups; specificity 70%/89% with comparable PPV in both groups (73%/80%). Parallel skin testing with combined patch test and evaluation of sIgE enhanced the value of sensitivity to 92% in the group A and specificity to 89% in the group B. For PPV corresponding figures were 85%/80%. CONCLUSIONS:APT was found to be more sensitive and specific method than SPT/sIgE in diagnosing delayed food allergy in children with AEDS. No age correlation between positive results of APT and oral food challenge and higher specificity of APT in older children confirm its accuracy in diagnosing delayed cow's milk allergy in all age groups of children. Combined skin prick and patch testing significantly enhances identification of food allergy in children with AEDS. The outcome of the APT with food does not seem to be influenced by age of children, but because of its variability of sensitivity and specificity, a diagnosis of food allergy should be confirmed by oral food challenge.
Severe acute pancreatitis is characterized by a poor prognosis with local and systemic complications, high morbidity and mortality. From the morphological standpoint, almost all patients suffering from severe forms of acute pancreatitis present various degree of pancreatic necrosis. In these patients the occurrence of infection of pancreatic necrosis certainly represents a very important prognostic factor as it has worldwide accepted as the leading cause of death. In addition, the discovery of an infected necrosis represents a crucial point in the treatment of these patients as it is the only clear-cut shift from medical to surgical treatment in necrotizing pancreatitis. Over the last years, earlier and more precise identification of pancreatic necrosis together with availability of new classes of antibiotics with documented activity against the most commonly involved bacteria and able to reach in therapeutic concentration the pancreatic necrosis give us the opportunity to perform some important controlled clinical trials on antibiotic prophylaxis in necrotizing acute pancreatitis. The great majority of these studies showed the usefulness of a prophylactic regimen (using antibiotics such as fluoroquinolones and carbapenems) in terms of reduction of pancreatic and extrapancreatic infections in comparison with untreated controls. Nevertheless, some questions on this topic still present controversial aspects such as the antibiotic of choice, the duration of treatment, the possible opportunistic infections with fungi and/or resistant strains. Antibiotics may prove very useful in patients with documented infected necrosis and high anaesthesiological risk unfit for surgical debridement and drainage; some initial experiences show the possibility that antibiotic treatment may be curative without surgery in these selected cases.
Pancreaticoduodenectomy is considered the standard procedure for the surgical treatment of the pancreatic head cancer. However, the extent of lymph node clearance associated to the procedure is still largely debated. Arguments in favour of an extended lymphadenectomy are the regular progression of lymph node invasion, without skip metastases, and the removal of the extrapancreatic neural plexus that is invaded in 52-72% of patients. Arguments against the extended lymphadenectomy are the failure of extended lymphadenectomy to improve survival in other cancers, and the severe diarrhoea that follows the skeletonisation of the superior mesenteric artery. After Ishikawa's paper, several retrospective studies supported a longer survival after an extended than after a standard lymphadenectomy, but as much retrospective studies failed to demonstrate any difference. Only three prospective randomised controlled trials have been performed so far. Unfortunately all are underpowered, and the substantial differences in the surgical procedures, in the adjuvant treatment, and in the length of follow-up make the comparison impossible. Only one study reports a significantly longer survival for lymph node positive patients who underwent an extended lymphadenectomy, but adjuvant treatment was not performed. Furthermore, the difference was of minimal clinical impact. At least two adequately powered prospective Randomised Controlled Trials including a true extended lymphadenectomy, and a standardised adjuvant treatment, would be required to answer the question. Unfortunately, we have not yet a standardised adjuvant (or neoadjuvant) treatment, and we do not know the impact of such treatment on the expected statistical difference in the survival after a standard or extended lymphadenectomy. The lot of work required to perform such trials probably doesn't worth the expected results.
PURPOSE:The power of correlation was assessed between chosen risk factors of cholelithiasis in order to establish the ranking of these factors in Podlasie inhabitants.MATERIAL AND METHODS:The study involved 169 patients hospitalized due for cholelithiasis (study group) and 202 patients without cholelithiasis (control group). Previous exposure of patients of both groups to the chosen risk factors of cholelithiasis was evaluated (based on a history questionnaire designed by the authors of the study). Two models of logistic regression were prepared (for men and women) for multivariate analysis.RESULTS:The ranking of the risk factors of cholelithiasis was established by analysing multiple correlation coefficients for the two models of logistic regression and their significance was determined with Wald's test. The significant risk factors for women included: overweight and obesity, age, diabetes, use of contraceptive pills, while for men these were: age, serum triglycerol level, obesity.CONCLUSIONS:The knowledge of risk factors of cholelithiasis in our population is the essence of health promoting actions. Obesity is the major risk factor in women and statistically significant in men. Promotion of appropriate eating habits can result in body mass reduction and may thus indirectly decrease other risk factors of cholelithiasis (incidence of type II diabetes and serum triglycerol level).
PURPOSE:The aim of the study was to obtain pharmacokinetic data for carbamazepine (CBZ) and its fractions not bound with proteins in bitherapy with lamotrigine (LTG), topiramate (TPM), vigabatrin (VGB) or valproic acid (VPA) in children and adolescents treated for epilepsy.MATERIAL AND METHODS:The participants of the presented investigations were fifty-five patients with epilepsy who were under control of The Department of Developmental Neurology, University of Medical Sciences in Poznaf. All of patients were treated with CBZ in bitherapy with LTG, TPM, VGB or VPA. The blood samples were taken under steady-state conditions, before the morning dose and subsequently every 3 or 2 for 24 h. The plasma levels of CBZ were determined using TDX analyzer (Abbott Diagnostic Division, USA). Free CBZ fraction was isolated with the use of ultrafiltration system (Amicon, USA). For pharmacokinetic calculations of total and free CBZ, one-compartment model was used according to standardized procedure.RESULTS:No significant differences in pharmacokinetic parameters of unbound CBZ in four groups of patients on bitherapy with CBZ and LTG, TPM, VGB or VPA were found. The changes in pharmacokinetics of total CBZ were related with difference in CBZ concentrations, area under curve (AUC), L/D/kg ratios and clearance (Cl)/kg. CBZ+VGB bitherapy led to higher total CBZ concentrations. In the group on bitherapy with CBZ+VPA, no increase in unbound CBZ was detected.CONCLUSIONS:Pharmacokinetic interactions of CBZ with LTG, TPM, VGB or VPA in children are associated only with the changes in total CBZ parameters.
The incidence of pancreatic carcinoma is recently increasing but the prognosis remains extremely poor. Widespread awareness of important clues to the diagnosis is particularly important to improve the prognosis. Dilatation of the main pancreatic duct on ultrasonograms and/or CT scans, hyperamylasemia incidentally found during routine blood examinations, and recent onset diabetes mellitus must lead to thorough imaging studies of the pancreas. Death from pancreatic carcinoma occurs in 0.2-1.9% of all diabetic patients, being more than 300 times frequent compared to general population. Diabetes may be the only clinical sign of pancreatic carcinoma in some patients. In our recent study, of 163 diabetic patients selected by several criteria who underwent ERCP screening, 12 patients (7.4%) proved to have pancreatic carcinoma. The prevalence of pancreatic carcinoma was more frequent in those with a recent onset (<3 years) of diabetes (13.7% (8/58)) than in those with a longer history (>3 years, 3.8% (4/105)). Furthermore, intraductal papillary mucinous neoplasm (IPMN) is reported to be associated with pancreatic carcinoma. Concomitant carcinoma was found in 9 of our series of 94 patients (9.5%) who underwent surgical resection of branch duct IPMN. Of particular interest is the fact that two of the 9 patients had carcinoma in situ that could be diagnosed only by cytology of the pancreatic juice. IPMN may be the only clue to the early diagnosis of pancreatic carcinoma presenting with no clinical symptoms or abnormalities on imaging studies.
PURPOSE The main research problem is to answer the following question: What ways of coping with situations of end-stage renal disease are used by the studied patients? To measure strategies of coping with stressful situations, The Ways of Coping Questionnaire (WCQ), devised by Folkman and Lazarus, was used. MATERIAL AND METHODS As examined group, the men with end-stage renal disease (N=113), including patients with a transplanted kidney (N=54) and dialyzed patients (N=59), was chosen. The analysis of these situations shows that from the psychological point of view, they are, to a certain extent, different situations. In this connection, the following question appears: Is there a relationship between the ways of coping with disease and the applied methods of treatment: dialysis therapy and transplantation? RESULTS Our findings shows that there are no perceptible, statistically essential differences in the applied strategies, evaluated by means of WCQ, between patients with a transplanted kidney and the ones dialyzed. Perhaps, despite the differences presented above in this argument, situations of patients with a transplanted kidney and the ones dialyzed are similar in some significant way, and this is reflected in the strategies they adopt. One of such common features for the situations of both groups of patients is a real, continuous threat of losing life. The situations studied are uncontrollable situations that can actually be influenced by nobody. CONCLUSIONS The results of research have been shown the lack of statistically essential differences in the applied strategies, evaluated by means of WCQ, between patients with a transplanted kidney and the dialyzed ones.
PURPOSE:The aim of this study was the assessment of the quality of life of children and adolescents with tension headaches in comparison with healthy peers.MATERIAL AND METHODS:The study was conducted on 135 middle school and high school students in Poznań and on 86 children with tension headaches, that were treated in the out-patient clinic of The Chair and Clinic of Development Age Neurology of Karol Marcinkowski University of Medical Sciences in Poznań. The research tool for both groups was Pediatric Quality of Life Inventory, version 4.0 (PedsQL 4.0) questionnaire.RESULTS:In the analysed groups dominated 14- and 16-year-old children. Among children with tension headaches, the ailments usually appeared once or twice a week in 39 (45%) of them. With the use of the PedsQL 4.0 questionnaire the following fields of activity were analyzed: biological, emotional, social functioning and mood.CONCLUSIONS:The biggest discrepancies between the group of healthy children and those with headaches were noted in the field of emotional functioning and mood. Adolescents with tension headaches more frequently reported the feeling of fear and sleep disorders in comparison to healthy students. Children with headaches look at the future in a more pessimistic way and are less satisfied with their lives.
Heart failure (HF) is a pathophysiological condition, when the heart can not provide adequate blood flow to the body organs. The main cause of HF is now ischemic heart disease (IHD), and the number of patients with HF in aging society is growing. HF is becoming the leading cause of death. Medical therapy does not provide satisfactory results in respect of symptoms and survival (5 year survival 28-40%). Therefore there is a trend towards early invasive methods of IHD treatment: percutaneous or surgical revascularisation and surgical reconstruction of myocardial damage. Most common surgical procedure in IHD is coronary artery bypass grafting (CABG). This treatment is safe and effective in patients with normal ventricular function (operative mortality 0.5%, 5 year survival >92%). Results in patients with impaired left ventricular (LV) function are better than conservative therapy, but still not satisfactory (operative mortality 8.4%, 5 year survival 65%). The modern surgical concept for improvement of ventricular function is left ventricular (LV) shape and volume restoration (SVR) accompanied by CABG. In cases of severe damage of myocardium resulting in left ventricular aneurysm or akinesia, SVR improves LV function and prevents further LV remodeling. At present it is under investigation whether SVR is of benefit for moderate-sized ventricles and NYHA class II symptoms. In case of ischemic mitral insufficiency mitral valve repair is a method of choice. The results of combined procedures in Heart Failure group (CABG + MV reconstruction or SVR) are better than CABG alone. Other surgical alternatives for HF treatment are: heart transplantation, ventricular assist devices (VAD), dynamic cardiomyoplasty, constrictive devices and cellular transplantation therapy. Heart transplantation is reserved for younger patients with less comorbidities. Shortage of donor organs and poor long-term results remains a main problem of such a treatment. VAD at present is still very expensive, and serves particularly as a "bridge to heart transplantation" or "bridge to recovery" rather than destination therapy. Despite of all achievements in medical or invasive HF treatment further basic and clinical works as well as new organization systems are necessary to find optimal strategies to reduce cost of care, improve quality of life and survival.
This paper is an attempt to examine nurses' attitudes towards transplantology, a branch of clinical medicine responsible for organ transplants. 84 registered nurses were interviewed. The questionnaire was of an audit character and it was filled under the supervision of interviewers. Nurses' knowledge about issues concerning transplantology was very incomplete. Very few nurses had their own experience in being a tissue donor (blood, bone marrow) for another human being. Many participants didn't see any difference between diagnosed death of brain stem and being a potential donor. Transplantology issues are still a taboo in many families. The majority of nurses involved in the study, thought they could be a donor ex mortuo. As an ex vivo donor, participants would agree to give their bone marrow. 9.5% of interviewed nurses didn't see anything wrong in buying organs.
The goal of the study was to determine the frequencies of occurrence of obesity and overweight among men from Podlasie region of Poland, as well as nutritional and environmental factors related to these conditions. During 9-year period (1987-1998), dietary habit of each of 556 men was evaluated three times using 24-hour consumption questionnaire. At the same time body mass index (BMI) was also calculated. BMI increased significantly from 26.2 kg/m2 to 27.6 kg/m2 during discussed period, while percentage of overweight grew up from 62.7% to 73.2% and percentage of obesity rose from 14.5% to 22.5%. Executed multiple regression analysis revealed a variety of predictors of obesity and overweight. Among nutritional factors, the increase of energy and carbohydrates (especially saccharose) in diet were the reasons of increasing BMI. Considering psychological, sociological and economical features, multi-shift work provoked increase of BMI, while decrease of BMI was induced by smoking. Observed increase of spread of overweight and obesity among men, had its nutritional and environmental reasons.
PURPOSE:To evaluate the effect of endurance exercise on the activity changes of selected lysosomal enzymes in particular types of rat muscle fibers, occurring by 0-4 days following the trial.MATERIAL AND METHODS:The experiment was performed on 3 month old male Wistar rats with body mass 250 +/- 25 g, exposed to single physical exercise on moving track (speed 17 m x min(-1), decline 0 degree, duration 87.5 +/- 27.5 min). Biochemical analyses were performed on homogenized fast-twitch FTa and FTb (m. gastrocnemius) and slow-twitch ST (m. soleus) muscle fibers of animals sacrificed 2 h (group II), 6 h (III) or 96 h (IV) after exercise and control group. The measurements considered protein concentration and the activities of beta-glucuronidase (beta-GRS), N-acetyl-beta-D-glucosaminidase (NAG), and arylsulphatase A (ASA).RESULTS:In FTa fibers, ASA and beta-GRS activities were elevated in all the exercised groups, with the most evident changes in animals tested 96 h post trial (group IV), while the peak of NAG activity was demonstrated 2 h after exercise (group II). In contrast, in FTb and ST fibers the levels of all the enzymes studied peaked 96 h after exercise, following the transient decrease in activity.CONCLUSIONS:The present study demonstrated that maximal running exercise, without the eccentric components, affects the activities of lysosomal enzymes in all types of rat muscular fibers. The lack of uniform activity profile for the lysosomal enzymes studied probably reflects the variety of their cellular functions.
PURPOSE Although many studies demonstrated expression of TNF family members in the course of B-CLL, there is a little known about relationships between soluble forms of these proteins. Furthermore, there is no study reported on effects of used therapy on this relation. The present study was designed to asses the relationships between the serum concentrations of sFas, sFasL and sTRAIL in patients with B-CLL regarding their correlation with clinical stage and used therapy. MATERIAL AND METHODS We studied 40 patients with B-cell chronic lymphocytic leukemia (B-CLL) at diagnosis, before treatment and four weeks after therapy. To measure sFas, sFasL and sTRAIL levels in serum commercially available ELISA kits were used. RESULTS We found increased concentrations of sFas in sera of all patients with B-CLL before treatment in comparison to the control group. There were no significant differences in concentrations of sFasL and sTRAIL between patients and control group. Increased sFasL concentrations after FC and CC therapy as well as decreased concentrations after 2CdA therapy in comparison to values before treatment were found. The concentrations of sTRAIL after FC and CC therapy were higher than those in patients before treatment. CONCLUSIONS Results obtained suggest that relationship between sFas, sFasL and sTRAIL in sera of patients with B-CLL before treatment may facilitate the growth B leukemic cells. Changes in these relations after therapy with FC and CC can make a contribution to inhibit B cells growth on the apoptosis way in this patient group.
UNLABELLED:The aim of the study was an analysis of correlation between mycological examination results and clinical features of changed toenails in patients that visited mycological laboratory due to suspected onychomycosis.MATERIAL AND METHODS:Samples of changed toenails were collected from 579 patients. From all that cases a precise patient's history was taken paying a special attention on previous antimycotic treatment. In the clinical examination features of toenail changes were estimated.RESULTS:Onychomycosis was confirmed by the mycological examination in 23.3% of patients and exclude in 56.3% of individuals. In 20.4% of all cases the fungi growth was not obtained despite of positive results of direct microscopic examination. Among the cultured fungi species the most frequently observed were strains of Trichophyton rubrum--46.6%. 46% of all patients were previously treated with antifungals but the therapy was not efficacious in 23% of them.CONCLUSIONS:In all the cases of toenail changes it is important to take a precise patient's history, because it has an essential influence on the results of diagnostic examinations. Diagnosing onychomycosis one cannot rely only on the clinical examination because in over 50% of patients with typical for onychomycosis toenail changes the mycological examination do not confirm fungal infection.
PURPOSE:The aim of the study was the evaluation of parodontium according to Community Peridental Index of Treatment Needs (CPITN) index in 455 students of The Medical and Dentistry Department of The Medical University of Białystok.MATERIAL AND METHODS:After the examination, the students filled a survey according to their own project concerning hygienic habits as well as smoking, sweet intake. The results underwent statistical analysis.RESULTS:There were 1334 (48.86%) sextants observed with healthy parodontium in the studied population. Gingivorrhoea was stated in 440 sextants (16.12%), more often in men than in women. Calculus was reveled in 790 sextants (28.94%) of the population. The number of sextants with code 3 was 1.76%. Sextants with shallow pockets were more numerous in women (37 sextants) than in men (11 sextants). Advanced changes in parodontium (code 4) were observed in 9 sextants (0.33%). On the basis of the analysis of treatment needs in the group of 455 students, it can be stated that only 24.62% of the examined subjects did not need parodontium treatment.CONCLUSIONS:The diagnosis of parodontopathy and the factor that can have harmful influence on the parodontium tissues in young people is a superior criterion in the fight with irreversible parodontium changes in adults.
PURPOSEAlterations in the redox state during chronic ethanol consumption are associated with the oxidation of ethanol via alcohol and aldehyde dehydrogenase. Among various antioxidants present in food, strong antioxidative effects have been attributed to polyphenols of green tea. The aim of the present study was to investigate the effect of green tea consumption during chronic ethanol intake on the activity of aldehyde dehydrogenase in the liver of rats during maturation and aging.MATERIALS AND METHODSThe activity of ALDH was measured in the livers of rats aged 2 (young), 12 (adult) and 24 months (old). The rats were fed with a control liquid Lieber DeCarli diet, control liquid diet containing green tea (3 g/l), ethanol liquid diet (with increasing ethanol dose from 2.3% to 7%) and ethanol liquid diet containing green tea.RESULTSChronic ethanol consumption significantly increased the liver ALDH activity in young and adult rats but decreased this activity in old animals. The drinking of green tea did not alter ALDH activity in ethanol-consuming rats. Drinking green tea alone significantly increased ALDH activity in young and adult rats but did not alter this activity in old rats.CONCLUSIONSThese results demonstrate that green tea administered during chronic ethanol consumption does not prevent the changes in the hepatic ALDH activity in the rats at each age.
Computational modelling, nano-bioscience and information technology in biology and medicine will play a major role in the interdisciplinary attempts to elucidate structures and functions of living systems. Developing tools capable to integrate the new advances and make benefit of them is crucial: accumulation of data and knowledge base with only storage and retrieval capabilities will have a poor impact if they are not made "active" or "operational". This is where models will play a central role in offering, not only sound ways for representation or simulation, but also the appropriate frames to put the players in the right place, with intra- and inter-level coupling and multisource handling. This paper advocated that sequential observations of multiple and complex mechanisms will be of limited interest to understand the inter-relations that are occurring at the same time, and therefore, that designing multimodal, multilevel and multiscale experiments, matched with these models, are of major importance.
