AIMS/HYPOTHESIS: Monogenic diabetes is estimated to account for 1-6% of paediatric diabetes cases in primarily non-consanguineous populations, while the incidence and genetic spectrum in consanguineous regions are insufficiently defined. In this single-centre study we aimed to evaluate diabetes subtypes, obtain the consanguinity rate and study the genetic background of individuals with syndromic and neonatal diabetes in a population with a high rate of consanguinity. METHODS: Data collection was carried out cross-sectionally in November 2021 at the paediatric diabetic clinic, Dr Jamal Ahmad Rashed Hospital, in Sulaimani, Kurdistan, Iraq. At the time of data collection, 754 individuals with diabetes (381 boys) aged up to 16 years were registered. Relevant participant data was obtained from patient files. Consanguinity status was known in 735 (97.5%) participants. Furthermore, 12 families of children with neonatal diabetes and seven families of children with syndromic diabetes consented to genetic testing by next-generation sequencing. Prioritised variants were evaluated using the American College of Medical Genetics and Genomics guidelines and confirmed by Sanger sequencing. RESULTS: A total of 269 of 735 participants (36.5%) with known consanguinity status were offspring of consanguineous families. An overwhelming majority of participants (714/754, 94.7%) had clinically defined type 1 diabetes (35% of them were born to consanguineous parents), whereas only eight (1.1%) had type 2 diabetes (38% consanguineous). Fourteen (1.9%) had neonatal diabetes (50% consanguineous), seven (0.9%) had syndromic diabetes (100% consanguineous) and 11 (1.5%) had clinically defined MODY (18% consanguineous). We found that consanguinity was significantly associated with syndromic diabetes (p=0.0023) but not with any other diabetes subtype. The genetic cause was elucidated in ten of 12 participants with neonatal diabetes who consented to genetic testing (homozygous variants in GLIS3 [sibling pair], PTF1A and ZNF808 and heterozygous variants in ABCC8 and INS) and four of seven participants with syndromic diabetes (homozygous variants in INSR, SLC29A3 and WFS1 [sibling pair]). In addition, a participant referred as syndromic diabetes was diagnosed with mucolipidosis gamma and probably has type 2 diabetes. CONCLUSIONS/INTERPRETATION: This unique single-centre study confirms that, even in a highly consanguineous population, clinically defined type 1 diabetes is the prevailing paediatric diabetes subtype. Furthermore, a pathogenic cause of monogenic diabetes was identified in 83% of tested participants with neonatal diabetes and 57% of participants with syndromic diabetes, with most variants being homozygous. Causative genes in our consanguineous participants were markedly different from genes reported from non-consanguineous populations and also from those reported in other consanguineous populations. To correctly diagnose syndromic diabetes in consanguineous populations, it may be necessary to re-evaluate diagnostic criteria and include additional phenotypic features such as short stature and hepatosplenomegaly.

• MeSH
• diabetes mellitus 1. typu * epidemiologie   genetika   MeSH
• diabetes mellitus 2. typu * epidemiologie   genetika   diagnóza   MeSH
• dítě MeSH
• kohortové studie MeSH
• lidé MeSH
• mutace genetika   MeSH
• nemoci novorozenců * genetika   MeSH
• novorozenec MeSH
• pokrevní příbuzenství MeSH
• proteiny přenášející nukleosidy genetika   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Irák MeSH

Biofilm formation is an effective survival strategy of plant-associated microorganisms in hostile environments, so the application of biofilm-forming and exopolysaccharide (EPS)-producing beneficial microbes to plants has received more attention in recent years. This study examined the ability of biofilm and EPS production of Bacillus subtilis and Bacillus thuringiensis strains under different NaCl concentrations (0, 50, 100, 200, and 400 mmol/L), pH values (5.5, 6.5, 7.5, and 8.5), and phosphate levels (0, 25, 50, and 100 mmol/L at 0 and 400 mmol/L NaCl). B. subtilis BS2 and B. thuringiensis BS6/BS7 strains significantly increased biofilm formation in a similar pattern to EPS production under salt stress. B. subtilis BS2/BS3 enhanced biofilm production at slightly acidic pH with a lower EPS production but the other strains formed considerably more amount of biofilm and EPS at alkaline pH. Interestingly, higher levels of phosphate substantially decreased biofilm and EPS production at 0 mmol/L NaCl but increased biofilm formation at 400 mmol/L salt concentration. Overall, contrary to phosphate, salt and pH differently influenced biofilm and EPS production by Bacillus strains. EPS production contributed to biofilm formation to some extent under all the conditions tested. Some Bacillus strains produced more abundant biofilm under salt and pH stress, indicating their potential to form in vivo biofilms in rhizosphere and on plants, particularly under unfavorable conditions.

• MeSH
• Bacillus subtilis fyziologie   metabolismus   účinky léků   MeSH
• Bacillus thuringiensis fyziologie   účinky léků   MeSH
• bakteriální polysacharidy * metabolismus   biosyntéza   MeSH
• biofilmy * účinky léků   růst a vývoj   MeSH
• chlorid sodný * farmakologie   metabolismus   MeSH
• fosfáty * metabolismus   farmakologie   MeSH
• koncentrace vodíkových iontů MeSH
• Publikační typ
• časopisecké články MeSH

Behavioral variant frontotemporal dementia (bvFTD) is characterized by profound and early deficits in social cognition (SC) and executive functions (EF). To date it remains unclear whether deficits of the respective cognitive domains are based on the degeneration of distinct brain regions. In 103 patients with a diagnosis of bvFTD (possible/probable/definite: N = 40/58/5) from the frontotemporal lobar degeneration (FTLD) consortium Germany cohort (age 62.5±9.4 years, gender 38 female/65 male) we applied multimodal structural imaging, i.e. voxel-based morphometry, cortical thickness (CTH) and networks of structural covariance via source based morphometry. We cross-sectionally investigated associations with performance in a modified Reading the Mind in the Eyes Test (RMET; reflective of theory of mind - ToM) and five different tests reflective of EF (i.e. Hamasch-Five-Point Test, semantic and phonemic Fluency, Trail Making Test, Stroop interference). Finally, we investigated the conjunction of RMET correlates with functional networks commonly associated with SC respectively ToM and EF as extracted meta-analytically within the Neurosynth database. RMET performance was mainly associated with gray matter volume (GMV) and CTH within temporal and insular cortical regions and less within the prefrontal cortex (PFC), whereas EF performance was mainly associated with prefrontal regions (GMV and CTH). Overlap of RMET and EF associations was primarily located within the insula, adjacent subcortical structures (i.e. putamen) and the dorsolateral PFC (dlPFC). These patterns were more pronounced after adjustment for the respective other cognitive domain. Corroborative results were obtained in analyses of structural covariance networks. Overlap of RMET with meta-analytically extracted functional networks commonly associated with SC, ToM and EF was again primarily located within the temporal and insular region and the dlPFC. In addition, on a meta-analytical level, strong associations were found for temporal cortical RMET correlates with SC and ToM in particular. These data indicate a temporo-frontal dissociation of bvFTD related disturbances of ToM and EF, with atrophy of the anterior temporal lobe being critically involved in ToM deficits. The consistent overlap within the insular cortex may be attributable to the multimodal and integrative role of this region in socioemotional and cognitive processing.

• MeSH
• exekutivní funkce * fyziologie   MeSH
• frontotemporální demence * patologie   diagnostické zobrazování   patofyziologie   psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• neuropsychologické testy * MeSH
• průřezové studie MeSH
• senioři MeSH
• sociální kognice MeSH
• teorie mysli * fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The aim of this study was to determine the prevalence of potentially inappropriate medications (PIMs) in nursing home residents across eight countries and investigate differences between residents with and without cognitive impairment, as well as those with and without life expectancy of six months or less. METHODS AND DEIGN: The study utilized the second edition of the STOPP-Frail criteria to operationalize PIMs in the baseline assessment of nursing home residents participating in the Services and Health for Elderly in Long TERm care (SHELTER) project. The data were collected between 2009 and 2012. The project was conducted in eight countries: Czech Republic, England, Finland, France, Germany, Italy, the Netherlands, and Israel. Cognitive impairment was measured by the cognitive performance scale (CPS). The presence of end-stage disease with a life expectancy of six months or less was recorded. The study included residents aged 60 years or older who underwent a valid medication assessment. RESULTS: Among the 3,832 eligible residents, 87.9% had at least one PIM. Specifically, 24.3%, 23.5%, 18.8%, and 19.3% of residents had one, two, three, and four or more PIMs, respectively. On average, each person was prescribed 2.16 PIMs. Cognitively impaired residents (n = 1999) had an average of 1.96 PIMs (SD 1.49) per person, while residents with a low CPS score (n = 1783) had an average of 2.40 PIMs (SD 1.57) per person, showing a statistically significant difference (P < 0.001). Similarly, NH residents with life expectancy of six months or less had an average of 1.66 PIMs (SD 1.30), whereas those without had an average of 2.17 PIMs (SD 1.55) (p < 0.001). The average number of PIMs varied across countries, ranging from 3.23 in Finland to 2.15 in the UK (P < 0.001). Anti-platelets and aspirin were the most prescribed PIMs, accounting for over 38.0% of prescriptions. CONCLUSIONS: This study highlights the high prevalence of PIMs among nursing home residents. However, PIMs were somewhat lower in residents with cognitive impairment and life expectancy of six months or less. Efforts must continue to improve the rationale behind prescribing practices in nursing homes.

• MeSH
• domovy pro seniory MeSH
• křehký senior MeSH
• lidé středního věku MeSH
• lidé MeSH
• nevhodné předepisování statistika a číselné údaje   MeSH
• pečovatelské domovy * MeSH
• prevalence MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• seznam potenciálně nevhodných léčiv * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Německo MeSH

BACKGROUND: Adolescence is often seen as an important period for further personality development. In today's world, it is therefore important to keep track of current trends in adolescents. One of them is addictive behaviour in the context of the online environment. Spending too much time online can have a negative impact on the quality of life of adolescents. It is therefore important to pay increased attention to this phenomenon and to respond adequately to the current situation. METHODS: Our study focuses on the prevalence of Internet addiction among Czech and Slovak adolescents. In total, 3,741 respondents participated in the project (N = 2,642 CZ; N = 1,099 SK); their ages ranged from 11 to 19 years (M = 14.38; SD ± 2.27). The research addressed differences among individual types of schools and between sexes in relation to Internet addiction. The research focused on adolescents attending secondary schools (ISCED 2 and 3) between the ages of 11 and 19 in the Czech and Slovak Republics. A questionnaire battery consisting of a sociodemographic questionnaire and the Internet Addiction Test (IAT) questionnaire was used for data collection. RESULTS: In relation to the category of Internet use, girls did not score higher than boys either in the Czech group F(1, 2112) = .089, p = .765, or in the Slovak group F(1, 927) < .001 p = .994. There is a significant effect of school type both in the Czech group F(4, 2100) = 11.483, p < .001, and in the Slovak group F(4, 859) = 2.859, p = .023. CONCLUSIONS: Our research indicates that some adolescents, particularly boys, face issues with excessive Internet use, affecting social interactions. Further studies in the Czech Republic could explore the link between psychosocial factors and adolescent Internet use. This highlights the need to raise awareness among professionals about Internet addiction in Czech and Slovak adolescents.

• MeSH
• chování mladistvých psychologie   MeSH
• dítě MeSH
• internet statistika a číselné údaje   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• návykové chování epidemiologie   psychologie   MeSH
• netholismus * epidemiologie   psychologie   MeSH
• prevalence MeSH
• průzkumy a dotazníky MeSH
• sexuální faktory MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH

BACKGROUND: The known impairments of the cardiovascular system in Parkinson ́s disease (PD) are caused by autonomic dysfunction and manifested mainly in postural hypotension, chronotropic insufficiency, and reduced heart rate variability. Other dysfunctions, mainly stress response, arrhythmia occurrence, and heart morphology changes, are still the subject of research. OBJECTIVES: To assess the heart rate and blood pressure reaction during exercise, advanced measurements of heart volumes and mass using cardiac magnetic resonance (CMR), and occurrence of arrhythmias in PD patients. METHODS: Thirty PD patients (19 men, mean age 57.5 years) without known cardiac comorbidities underwent bicycle ergometry, electrocardiogram Holter monitoring and CMR. Exercise and CMR parameters were compared with controls (24 subjects for ergometry, 20 for CMR). RESULTS: PD patients had lower baseline systolic blood pressure (SBP) (117.8 vs. 128.3 mmHg, p < 0.01), peak SBP (155.8 vs. 170.8 mmHg, p < 0.05), and lower heart rate increase (49.7 vs. 64.3 beats per minute, p < 0.01). PD patients had higher indexed left and right ventricular end-diastolic volumes (68.5 vs. 57.3, p = 0.003 and 73.5 vs. 61.0 mL/m2 , respectively) and also indexed left and right ventricular end-systolic volumes (44.1 vs. 39.0, p = 0.013 and 29.0 vs. 22.0 mL/m2 , p = 0.013, respectively). A high prevalence of atrial fibrillation (8 subjects, 26.7%) was found. CONCLUSIONS: This novel study combining functional and structural approaches showed that PD is linked with weaker blood pressure and heart rate reaction during exercise, increased myocardial mass and heart volumes compared to controls, and a high prevalence of atrial fibrillation.

• MeSH
• elektrokardiografie MeSH
• fibrilace síní * komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• Parkinsonova nemoc * komplikace   epidemiologie   MeSH
• srdce MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Synovial sarcoma is a relatively common soft tissue tumor characterized by highly specific t(X;18)(p11;q11) translocation resulting in the fusion of SS18 with members of SSX gene family. Typically, detection of SS18 locus rearrangement by fluorescence in situ hybridization or SS18 :: SSX fusion transcripts confirms the diagnosis. More recently, immunohistochemistry (IHC) for SS18-SSX chimeric protein (E9X9V) and C-terminus of SSX (E5A2C) showed high specificity and sensitivity for synovial sarcoma. This study screened a cohort of >1000 soft tissue and melanocytic tumors using IHC and E9X9V and E5A2C antibodies. Three percent (6/212) of synovial sarcomas were either negative for SS18-SSX or had scattered positive tumor cells (n=1). In these cases, targeted RNA next-generation sequencing detected variants of SS18 :: SSX chimeric transcripts. DNA methylation profiles of 2 such tumors matched with synovial sarcoma. A few nonsynovial sarcoma tumors (n=6) revealed either focal SS18-SSX positivity (n=1) or scattered positive tumor cells. However, targeted RNA next-generation sequencing failed to detect SS18 :: SSX transcripts in these cases. The nature of this immunopositivity remains elusive and may require single cell sequencing studies. All synovial sarcomas showed positive SSX IHC. However, a mosaic staining pattern or focal loss of expression was noticed in a few cases. Strong and diffuse SSX immunoreactivity was also seen in epithelioid sclerosing osteosarcoma harboring EWSR1 :: SSX1 fusion, while several sarcomas and melanocytic tumors including cellular blue nevus (5/7, 71%) revealed focal to diffuse, mostly weak to intermediate SSX staining. The SS18-SSX and SSX IHC is a useful tool for synovial sarcoma differential diagnosis, but unusual immunophenotype should trigger molecular genetic testing.

• MeSH
• diferenciální diagnóza MeSH
• fúzní onkogenní proteiny genetika   metabolismus   MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádory měkkých tkání * diagnóza   genetika   MeSH
• rekombinantní fúzní proteiny genetika   MeSH
• RNA MeSH
• synoviom * diagnóza   genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Buprenorfin patří mezi silné opioidy. Zároveň je řazen i mezi tzv atypické opioidy. Ty působí ještě i na jiném než p opioidním mechanismu. Buprenorfin je parciální agonista na p opioidních receptorech, antagonista na k a 6 receptorech a agonista na ORLI (opioid receptor-like 1). Buprenorfin má minimum nežádoucích účinků. Aplikační místa se doporučuje pr

Buprenorphine belongs between very strong opioids. At the same time, it is categorized among atypical opioids. They besides effect on something else then p opioid mechanism. Buprenorphine is a partial agonist on m opioid receptors, antagonist on k and 6 receptors and agonist on ORLI (opioid receptor-like 1). In case of local reaction is recommended to use dexpanthenol on application area as a precaution, it is advisable to do so after application as well. In case of adverse reaction, we treat the skin with local corticosteroids. It could be used preventively as well.

Prognóza nemocných s neresekovatelným či metastazujícím karcinomem prsu s pozitivitou receptoru 2 pro lidský epidermální růstový faktor (human epidermal growth factor receptor 2, HER2) se významně zlepšila zavedením nových anti-HER2 přípravků. Současným léčebným standardem 1. linie je kombinace taxanů s pertuzumabem a trastuzumabem. Možnosti terapie pokročilého HER2 pozitivního karcinomu prsu se stále rozvíjejí, k dispozici v dalších liniích léčby jsou konjugáty cytostatika s protilátkou a malé molekuly tyrozinkinázových inhibitorů. Zásadní zlepšení léčebných výsledků přináší především trastuzumab deruxtekan (T-DXd), který prokázal výjimečnou účinnost u pacientek s HER2 pozitivním metastazujícím karcinomem prsu v klinických studiích DESTINY-Breast01 a DESTINY-Breast03. Předkládaná kazuistika dokládá vysokou účinnost tohoto přípravku ve 3. linii léčby nemocné s prognosticky nepříznivým HER2 pozitivním karcinomem prsu.

The prognosis of patients with unresectable or metastatic breast cancer with positive human epidermal growth factor receptor 2 (HER2) has significantly improved with the introduction of new anti-HER2 agents. The current first-line treatment standard is a combination of taxanes with pertuzumab and trastuzumab. Treatment options for advanced HER2-positive breast cancer continue to evolve, with antibody-drug conjugates and small molecule tyrosine kinase inhibitors available in subsequent lines of therapy. A significant improvement in treatment outcomes is primarily brought by trastuzumab deruxtecan, which has demonstrated exceptional efficacy in patients with HER2-positive metastatic breast cancer in the clinical studies DESTINY-BreastOI and DESTINY-Breast03. The presented case report confirms the high efficacy of this drug in the third-line treatment of a patient with a prognostically unfavorable HER2-positive breast cancer.

Předložená kazuistika popisuje případ pacientky s vysoce rizikovým, BRAF V600E mutovaným maligním melanomem, u které i přes adjuvantní cílenou terapii dabrafenibem plus trametinibem došlo po 9 měsících po dokončení léčby k rozvoji plicního relapsu. Následná systémová léčba cílenou terapií enkorafenibem plus binimetinibem navodila po 9 měsících kompletní remisi, avšak za dalších 18 měsíců došlo k rychlé progresi onemocnění s rozvojem mozkových metastáz a úmrtí pacientky.

The presented case report describes the case of a patient with high-risk, BRAF V600E mutated malignant melanoma, who, despite adjuvant targeted therapy with dabrafenib plus trametinib, developed a pulmonary relapse 9 months after the completion of treatment. Subsequent systemic treatment with targeted therapy with encorafenib plus binimetinib induced a complete remission after 9 months, but over the next 18 months, the disease rapidly progressed with the development of brain metastases and the patient’s death.