Influence of different spectra of NOTCH3 variants on the clinical phenotype of CADASIL - experience from Slovakia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary vascular disorder causing ischaemic attacks and strokes in middle-aged adults. Though the clinical spectrum includes some typical symptoms, recognition of the disease, especially at an earlier stage, is very difficult because of the highly variable manifestation and incomplete clinical picture. Characteristic brain MRI findings and the presence of pathogenic variants in the NOTCH3 gene are fundamental for CADASIL diagnosis. In this paper, we provide the first comprehensive report on CADASIL patients from Slovakia. Altogether, we identified 23 different pathogenic variants in 35 unrelated families. In our cohort of patients with clinical suspicion of CADASIL, we found a causal genetic defect and confirmed the diagnosis in 10.2% of cases. We present the case reports with up-to-date unpublished NOTCH3 variants and describe their phenotype-genotype correlation: p.(Cys65Phe), p.(Pro86Leu/Ser502Phe), p.(Arg156*), p.(Cys408Arg), p.(Tyr423Cys), p.(Asp1720His), and p.(Asp1893Thrfs*13). The most frequently described location for pathogenic variants was in exon 4, whereas the most common single variant was p.Arg1076Cys in exon 20. Based on the results of our study, we propose a re-evaluation of the criteria for the selection of patients suitable for NOTCH3 gene analysis. We hereby state that the currently used protocol of a high score requirement is not ideal for assessing molecular analysis, and it will be desirable to be less strict in criteria for genetic testing.

Motivational climate and attitudes to change: a hospital study.

Change can be highly motivating when it is perceived as results-oriented, well planned and well communicated. However, there appears to be a lack of evidence on the actual existence of such relationships between motivational climate and attitudes to change in management literature, especially under the specific conditions of health care organisations in Slovakia. Using a sample of 243 employees of the University Hospital Bratislava, the present study has investigated the validity of the assumption that: (i) low motivational climate will represent an inhibitor to change, and vice versa, (ii) the more attention is being paid by the organisation's management to implementation of change, resulting in the staff having positive attitudes to change, the higher the motivational climate within the organisation will be. The findings indicate that motivational climate of the hospital can be heavily influenced by the manner in which the change is being managed. Moreover, not only how change is being managed, but also how it is understood and accepted by the employees, as well as which outcomes the change results in, have significant effects on the perceived motivational climate. The results also show that to maintain the high motivational climate, thus stimulating desired behaviours in the staff, the hospital managers should keep, among other things, (i) encouraging the workers to make a creative contribution, (ii) informing them about the reasons why changes are being made, (iii) showing them how their work objectives relate to where the hospital is heading and that the cost of the current changes will not outweight the benefits, and (v) ensuring that adequate training is available to equip people for changes and giving them the support they need to cope with change. Last, but not least, the present study helps to demonstrate the importance of attitudes as a force that is powerful in determining work output. (Tab. 3, Ref. 37.)

[Topical diagnosis of comatose states]. / Moznosti topickej diagnostiky komatóznych stavov.

Topical diagnosis of comatose states is based on the concept of cranio-caudal development of cerebral dysfunction. Neurological examination of comatose patients is focused on assessment of the pathophysiological cause of impaired consciousness, localization of the functional or structural cerebral disorder and on evaluation of the progression or regression of the lesion. It is based on findings from the semiology of comatose states whereby the depth of unconsciousness, evaluation of diencephalic and stem reflexes, ocular symptoms, motorics and vegetative symptoms are emphasized.