Implications of introducing case based radiological images in anatomy on teaching, learning and assessment of medical students: a mixed-methods study.

BACKGROUND: Introducing radiological anatomy in the preclinical curriculum can increase the understanding of Anatomy. Regardless of the integration when teaching anatomy, it is essential to maintain oversight as to what and how much is being taught. In addition, the knowledge requirements for preclinical students should be considered. The purpose of this kind of integration is that the student should be able to apply the knowledge which can help them better understand anatomy and not to make the course more challenging. This study aimed to understand whether adding radiological images would increase the difficulty level of the questions. METHODS: We introduced radiological images, including X Rays, CT scans and MRIs, when teaching anatomy in the preclinical curriculum. A class of 99 students were tested using A-type MCQs (n = 84). All 84 questions were categorized on whether they were case-based with or without a radiological image. The item analysis of both groups of test questions was then compared based on their difficulty and discrimination index. A qualitative student perception regarding the inclusion of radiological images in anatomy was also measured using a questionnaire with a 5-point Likert scale. RESULTS: The results showed that the performance level of the students was similar when comparing the test questions in both groups. The item analysis of the MCQs in the two groups revealed that by integrating radiological images when teaching anatomy, the various parameters in both groups of test questions were in the same range. More than 80% of the students felt that radiological images facilitate the achievement of learning outcomes and help to apply their knowledge in clinical contexts. The study's findings reported that the rate of satisfaction by including radiological images when teaching anatomy is high. CONCLUSION: Recognition and interpretation of images are essential in an undergraduate medical program. Students found it helpful when radiological images were introduced to them when teaching anatomy. Since the students' performance in summative exams in both groups of questions was in the same range, the findings also point out that adding radiological images when teaching anatomy does not increase the difficulty of the subject.

Glucose-level dependent brain hypometabolism in type 2 diabetes mellitus and obesity.

BACKGROUND: Metabolic syndrome and its individual components lead to wide-ranging consequences, many of which affect the central nervous system. In this study, we compared the [18F]FDG regional brain metabolic pattern of participants with type 2 diabetes mellitus (T2DM) and non-DM obese individuals. METHODS: In our prospective study, 51 patients with controlled T2DM (ages 50.6 ± 8.0 years) and 45 non-DM obese participants (ages 52.0 ± 9.6 years) were enrolled. Glucose levels measured before PET/CT examination (pre-PET glucose) as well as laboratory parameters assessing glucose and lipid status were determined. NeuroQ application (NeuroQTM 3.6, Syntermed, Philips) was used to evaluate regional brain metabolic differences. [18F]FDG PET/CT (AnyScan PC, Mediso) scans, estimating brain metabolism, were transformed to MNI152 brain map after T1 registration and used for SPM-based group comparison of brain metabolism corrected for pre-PET glucose, and correlation analysis with laboratory parameters. RESULTS: NeuroQ analysis did not reveal significant regional metabolic defects in either group. Voxel-based group comparison revealed significantly (PFWE<0.05) decreased metabolism in the region of the precuneus and in the right superior frontal gyrus (rSFG) in the diabetic group as compared to the obese patients. Data analysis corrected for pre-PET glucose level showed a hypometabolic difference only in the rSFG in T2DM. Voxel-based correlation analysis showed significant negative correlation of the metabolism in the following brain regions with pre-PET glucose in diabetes: precuneus, left posterior orbital gyrus, right calcarine cortex and right orbital part of inferior frontal gyrus; whilst in the obese group only the right rolandic (pericentral) operculum proved to be sensitive to pre-PET glucose level. CONCLUSIONS: To our knowledge, this is the first study to perform pre-PET glucose level corrected comparative analysis of brain metabolism in T2DM and obesity. We also examined the pre-PET glucose level dependency of regional cerebral metabolism in the two groups separately. Large-scale future studies are warranted to perform further correlation analysis with the aim of determining the effects of metabolic disturbances on brain metabolism.

A population-based epidemiological study of neuromyelitis optica spectrum disorder in Hungary.

BACKGROUND AND PURPOSE: The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO Diagnosis (IPND) criteria. METHODS: A retrospective population-based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re-evaluation from multiple sources. Crude and sex- and serostatus-specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person-years) from 2006 to 2015 were estimated and age-adjusted rates were determined. RESULTS: Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 [95% confidence interval (CI) 1.52-2.28] per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person-years provided an incidence rate of 1.32 (95% CI 1.08-1.61) per 1 000 000 person-years. Age-adjusted prevalence was 1.87 (95% CI 1.56-2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98-1.46) per 1 000 000 person-years. CONCLUSIONS: In this first report of a large population-based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.

Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms.

Antifungal lock therapy has received significant interest in the last few years because the frequently usage of intravascular devices is associated with an increasing number of catheter-related bloodstream infections caused by Candida species. Antifungal combinations with synergistic interaction can be a good choice for antifungal lock therapy; therefore, interactions were examined between two echinocandins (caspofungin and micafungin) and the chitin synthesis inhibitor nikkomycin Z against Candida albicans and C. parapsilosis biofilms. Susceptibility was evaluated using the XTT-based checkerboard microdilution method, while the nature of interactions was assessed by calculating fractional inhibitory concentration indices and using the Bliss independence model. Mathematic-based evaluations were supplemented with fluorescent LIVE/DEAD viability assay. The results obtained by statistical interaction analyses correlated well with the viability assay. The tested echinocandins with nikkomycin Z caused an extended cell death and the structure of the biofilm was sparse compared to the control, especially for C. albicans. The findings support the simultaneous usage of nikkomycin Z and caspofungin or micafungin in alternative therapies such as the antifungal lock therapy. SIGNIFICANCE AND IMPACT OF THE STUDY: Antifungal lock therapy can be a potential therapeutic approach to eradicate the intraluminal Candida biofilms; however, there is no approved lock strategy against fungal species so far. The results of this study provide valuable evidence that nikkomycin Z acts synergistically in combination with caspofungin or micafungin against biofilms. In addition, this synergy was more pronounced for micafungin combined with nikkomycin Z. Therefore, nikkomycin Z can be considered as a potential agent in antifungal lock therapy especially with micafungin against C. albicans or C. parapsilosis biofilms.

Activity of exogenous tyrosol in combination with caspofungin and micafungin against Candida parapsilosis sessile cells.

AIMS: Fungal quorum-sensing molecules may have an inhibitory effect as adjuvant against Candida biofilms. Therefore, in vitro activity of caspofungin and micafungin was evaluated against Candida parapsilosis biofilms in the presence of tyrosol. METHODS AND RESULTS: Interactions were assessed using fractional inhibitory concentration index (FICI) determination, metabolic activity-based time-kill experiments and scanning electron microscopy (SEM). Tyrosol caused 1-16-fold and 2-32-fold decrease in median caspofungin and micafungin MICs respectively. Based on FICI, synergy was observed in isolates 27001 and 17820 with caspofungin and 27001 with micafungin. In time-kill experiments, the metabolic activity reduction was higher for micafungin compared to caspofungin at 24 h especially when used in 64 and 256 mg l-1 concentrations. In the case of micafungin, the 256 mg l-1  + 1 mmol l-1 combination caused significantly higher decrease in metabolic activity compared to the corresponding concentration alone (256 mg l-1 ) at 24 h (P < 0·05). SEM confirmed the higher killing effect of tested echinocandins with tyrosol. CONCLUSIONS: Considerable metabolic activity reduction and cell damage was detected for combinations especially in the case of micafungin. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings support the development of new alternative therapeutic strategies against C. parapsilosis biofilms.

Prediction of myocardial tissue loss by quantitative densitometric myocardial blush parameters following ST-elevation myocardial infarction.

UNLABELLED: Tissue level myocardial perfusion is one of the most important prognostic factors after successful recanalisation of the occluded coronary artery in patients suffering acute ST elevation myocardial infarction (STEMI). The primary objective of the present study was to examine the relationship between videodensitometric myocardial perfusion parameters as assessed on coronary angiograms directly following successful recanalization therapy and magnetic resonance imaging (MRI)-derived myocardial tissue loss late after STEMI. The study comprised 29 STEMI patients. Videodensitometric parameter G(max)/T(max) was calculated to characterize myocardial perfusion, derived from the plateau of grey-level intensity (G(max)), divided by the time-to-peak intensity (Tmax). Myocardial loss index (MLI) was assessed by cardiac MRI following 376 ± 254 days after PCI. RESULTS: Significant correlations could be demonstrated between MLI and G(max) (r = 0.36, p = 0.05) and G(max)/T(max) (r = 0.40, p = 0.03) using vessel masking. Using receiver operating characteristic curve analysis, G(max)/T(max) < 2.17 predicted best MLI = 0.3, 0.4, 0.5 and 0.6 with good sensitivity and specificity data, while G(max)/T(max) < 3.25 proved to have a prognostic role in the prediction of MLI = 0.7. CONCLUSIONS: Selective myocardial tissue level perfusion quantitative measurement method is feasible and can serve as a good predictor of myocardial tissue loss following STEMI and revascularization therapy.

'Wind-up' in Parkinson's disease: A functional magnetic resonance imaging study.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder mainly marked by selective degeneration of dopaminergic neurons that leads to disabling motor and cognitive impairment. This condition is less widely appreciated as a disease associated with a substantial variety of pain syndromes, although the prevalence of pain is relatively high. Repeated painful stimulation of peripheral nerves can cause pain 'wind-up' if the frequency of the stimulation is adequate and specifically stimulates the afferent C-fibres. We presumed that in case of PD, pain or pain severeness might be frequently caused by the aggravation of the 'wind-up' phenomenon due to any central or peripheral lesions or functional alterations. METHODS: To test for this hypothesis, we compared three groups (patients with left- and right-dominant PD and control subjects) using functional magnetic resonance imaging and thermally induced pain. RESULTS: Patient showed higher average 'wind-up' scores, compared to the healthy subjects, with lower values on the more affected sides compared to the less affected ones. In group level comparisons, patients had higher activation during 'wind-up' compared to control subjects in two main areas; these were the posterior division of cingulate gyrus and the precuneus cortex. In case of patients, further analyses showed that applied heat pain on the less affected side elicited higher activation in the supramarginal and postcentral gyri. CONCLUSIONS: These differences may arise from the deficiency in the efferent information, as well as the alterations in the central processing. It is highly likely that both processes contribute to this phenomenon simultaneously.

Bile acids inhibit Na⁺/H⁺ exchanger and Cl⁻/HCO3⁻ exchanger activities via cellular energy breakdown and Ca²âº overload in human colonic crypts.

Bile acids play important physiological role in the solubilisation and absorption of dietary lipids. However, under pathophysiological conditions, such as short bowel syndrome, they can reach the colon in high concentrations inducing diarrhoea. In this study, our aim was to characterise the cellular pathomechanism of bile-induced diarrhoea using human samples. Colonic crypts were isolated from biopsies of patients (controls with negative colonoscopic findings) and of cholecystectomised/ileum-resected patients with or without diarrhoea. In vitro measurement of the transporter activities revealed impaired Na⁺/H⁺ exchanger (NHE) and Cl⁻/HCO3⁻ exchanger (CBE) activities in cholecystectomised/ileum-resected patients suffering from diarrhoea, compared to control patients. Acute treatment of colonic crypts with 0.3 mM chenodeoxycholate caused dose-dependent intracellular acidosis; moreover, the activities of acid/base transporters (NHE and CBE) were strongly impaired. This concentration of chenodeoxycholate did not cause morphological changes in colonic epithelial cells, although significantly reduced the intracellular ATP level, decreased mitochondrial transmembrane potential and caused sustained intracellular Ca²âº elevation. We also showed that chenodeoxycholate induced Ca²âº release from the endoplasmic reticulum and extracellular Ca²âº influx contributing to the Ca²âº elevation. Importantly, our results suggest that the chenodeoxycholate-induced inhibition of NHE activities was ATP-dependent, whereas the inhibition of CBE activity was mediated by the sustained Ca²âº elevation. We suggest that bile acids inhibit the function of ion transporters via cellular energy breakdown and Ca²âº overload in human colonic epithelial cells, which can reduce fluid and electrolyte absorption in the colon and promote the development of diarrhea.

UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes.

Ultraviolet (UV) B is the most prominent physical carcinogen in the environment leading to the development of various skin cancers. We have previously demonstrated that the human ortholog of the Arabidopsis thaliana constitutive photomorphogenesis 1 (COP1) protein, huCOP1, is expressed in keratinocytes in a UVB-regulated manner and is a negative regulator of p53 as a posttranslational modifier. However, it was not known whether huCOP1 plays a role in mediating the UVB-induced early transcriptional responses of human keratinocytes. In this study, we report that stable siRNA-mediated silencing of huCOP1 affects the UVB response of several genes within 2 h of irradiation, indicating that altered huCOP1 expression sensitizes the cells toward UVB. Pathway analysis identified a molecular network in which 13 of the 30 examined UVB-regulated genes were organized around three central proteins. Since the expression of the investigated genes was upregulated by UVB in the siCOP1 cell line, we hypothesize that huCOP1 is a repressor of the identified pathway. Several members of the network have been implicated previously in the pathogenesis of non-melanoma skin cancers; therefore, clarifying the role of huCOP1 in these skin diseases may have clinical relevance in the future.

Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy.

BACKGROUND: Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy. AIM: To assess the disease course and frequency of relapse of Crohn's disease (CD) following discontinuation of biological therapy, and to determine predictive factors for relapse. METHODS: One hundred twenty-one CD patients who had achieved clinical remission following 1 year of biological therapy and for whom biological therapy was then discontinued participated in this prospective observational study. Eighty-seven CD patients had received infliximab and 34 adalimumab. The definition of relapse was an increase of >100 points in CDAI to at least a CDAI of 150 points. RESULTS: Biological therapy was restarted within 1 year of treatment cessation in 45% of patients. Logistic regression analysis revealed that previous biological therapy (P = 0.011) and dose intensification during the 1-year course of biological therapy (P = 0.024) were associated with the need for and the time to the restarting of biological therapy. Smoking was observed to have an effect that was not statistically significant (P = 0.053). CONCLUSIONS: Biological therapy was restarted a median of 6 months after discontinuation in almost half of Crohn's disease patients in who had been in clinical remission following 1 year of biological therapy. These results suggest that, in the event of the presence of certain predictive factors, biological therapy should probably be continued for more than 1 year by most patients.

Sensitivity and specificity of Addenbrooke's Cognitive Examination, Mattis Dementia Rating Scale, Frontal Assessment Battery and Mini Mental State Examination for diagnosing dementia in Parkinson's disease.

INTRODUCTION: Among the non-motor features of Parkinson's disease (PD), cognitive impairment is one of the most troublesome problems. Highly sensitive and specific screening instruments for detecting dementia in PD (PDD) are required in the clinical practice. METHODS: In our study we evaluated the sensitivity and specificity of different neuropsychological tests (Addenbrooke's Cognitive Examination, ACE; Frontal Assessment Battery, FAB and Mattis Dementia Rating Scale, MDRS) in 73 Parkinson's disease patients without depression. By receiver operating characteristic curve analysis, these screening instruments were tested against the recently established clinical diagnostic criteria of PDD. RESULTS: Best cut-off score for ACE to identify PDD was 80 points (sensitivity = 74.0%, specificity = 78.1%). For FAB the most optimal cut-off value was 12 points (sensitivity = 66.3%, specificity = 72.2%); whereas for MDRS it was 125 points (sensitivity = 89.8%, specificity = 98.3%). Among the examined test batteries, MDRS had the best clinicometric profile for detecting PDD. CONCLUSION: Although the types of applied screening instruments might differ from movement disorder clinic to clinic within a country, determination of the most specific and sensitive test for the given population remains to be an important task. Our results demonstrated that the specificity and sensitivity of MDRS was better than those of ACE, FAB and MMSE in Hungary. However, further studies with larger sample size and more uniform criteria for participation are required to determine the most suitable screening instrument for cognitive impairment.

Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn's disease.

BACKGROUND: Adalimumab is a fully human monoclonal antibody targeting tumour necrosis factor with proven efficacy in the treatment of Crohn's disease (CD). AIM: To investigate the predictors of medium-term clinical efficacy and mucosal healing during adalimumab therapy, in patients with CD, in specialised centres approved for biological therapy in Hungary. METHODS: Data capture of the 201 CD patients was standardised and prospective (male/female: 112/89, median age: 33.0 years, duration: 8 years). Previous infliximab therapy had been administered in 48% of patients, concomitant steroids in 41%, azathioprine in 69% and combined therapy in 27% of patients. RESULTS: Overall clinical response and remission rates at 24 weeks were 78% and 52%, respectively; at 52 weeks were 69% and 44%, respectively. Endoscopic improvement and healing were achieved in 43% and 24% of patients. In a logistic regression model, clinical efficacy and CRP at week 12, need for combined immunosuppression at induction, shorter disease duration and smoking were identified as independent predictors for 12-month clinical outcome, whereas CRP at week 12, clinical remission at week 24, inflammatory parameters and nonsmoking were associated to endoscopic improvement/healing. Intensification to weekly dosing was needed in 16% of patients. Parallel azathioprine therapy and clinical remission at week 12 were inversely associated with dose escalation. CONCLUSIONS: Clinical efficacy and normalised CRP at week 12 (early deep clinical remission) are associated with medium-term clinical efficacy and mucosal healing during adalimumab therapy, whereas need for combined immunosuppression at induction and smoking status are predictors for non-response. Parallel azathioprine therapy may decrease the probability for dose escalation.

Clinical trial: Preliminary efficacy and safety study of a new Budesonide-MMX® 9 mg extended-release tablets in patients with active left-sided ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease with relapses. Many patients need systemic corticosteroids to induce clinical remission. AIM: Efficacy and safety of Budesonide-MMX® 9 mg tablets, a new oral, extended-release formulation, were evaluated in patients suffering from active, left-sided UC with colitis activity index (CAI) <14. METHODS: 36 patients were treated once daily for 4 weeks with Budesonide-MMX® 9 mg tablets or placebo. In an additional 4-week period, all patients received Budesonide-MMX®. CAI, endoscopic index and histology were assessed after 4 and 8 weeks. Primary end-point was remission, and/or CAI reduction by 50% after 4 weeks. Morning cortisol was assayed after 4 and 8 weeks, and a short ACTH-test was performed at week 8. RESULTS: 32 patients were analysed. After 4 weeks, 47.1% of the patients in the Budesonide-MMX® 9 mg tablets group achieved the primary end-point vs. 33.3% of patients on placebo. In addition, 47.1% of budesonide patients and another 33.3% of placebo recipients improved without remission by 4 weeks. The CAI reduction was significant with Budesonide (p<0.0001) tablets and not with placebo (p=0.1). Neither morning cortisol nor pituitary-adrenal axis was more frequently suppressed with Budesonide tablets than with placebo. CONCLUSIONS: Budesonide-MMX® 9 mg tablets induced a fast and significant clinical improvement of active left-sided UC without suppression of adrenocortical functions and without important toxicity EudraCT number 2004-000896-33.