Východisko. Přestože byly již popsány bodové mutace v genu pro prekurzor amyloidního proteinu u nemocných s Alzheimerovou demencí, stále existuje část nemocných, u nichž nebyla tato mutace nalezena a nebyla rovněž nalezena vazba k dalším uvažovaným genetickým lokusům na chromozomech 14 a 19. Proto byla skupina osob s Alzheimerovou demencí podrobena testování na přítomnost mutace v APP genu (v pozici 717). Metody a výsledky. U vybrané skupiny osob s Alzheimerovou demencí (AD) jsou nacházeny mutace v genu pro prekurzor amyloidního proteinu v pozici 717 jeho transmembránové domény. Analyzovali jsme genomovou DNA mozkové tkáně osob české národnosti pro přítomnost této mutace pomocí polymerázové řetězové reakce s následným ověřením sekvenační analýzou. U každé osoby byla prováděna genetická analýza z mozkových oblastí lobus frontalis, lobus temporalis, lobus parietalis a hippocampus. Použité metody byly polymerázová řetězová reakce (PCR), sekvenace. Z celkového počtu 18 osob s prokázanou Alzheimerovou demencí a 6 nepříbuzných osob bez histopatologických znaků Alzheimerovy demence po 90. roce života, byly nalezeny 3 sekvenační změny v pozici 717 exonu 17 transmembránové domény prekurzoru beta-4 amyloidního glykoproteinu. V prvním případě se jednalo o záměnu thyminu za adenin v kodonu 717, ve druhém případě se jednalo o záměnu cytosinu za thymin, ve třetím případě byla nalezena sporadická mutace guaninu za thymin v kodonu 717. Závěry. Ukazuje se, že kodon 717 by mohl být tzv. hot-spot místem preferovaným pro přednostní vznik mutací v kodonu 717 genu pro amyloidní proteinový prekurzor (APP).

Background. Although locus mutations in the gene for the amyloid precursor protein were already described in patients with Alzheimer's disease, there still are some patients where this mutation was not found and no link was found with other possible genetic loci on chromosomes 14 and 19. Therefore a group of subjects with Alzheimer's disease was subjected to tests for the presence of a mutation in the APP gene (in position 717). Methods and Results. In a selected group of subjects with Alzheimer's disease (AD) in the gene for amyloid precursor protein in position 717 mutations of its transmembraneous region are found. The authors analyzed the genome DNA of cerebral tissue of Czech subjects for the presence of this mutation by means of the polymerase chain reaction with subsequent verification by sequencing analysis. In every subject genetic analyses from cerebral areas of the frontal lobe, temporal lobe, parietal lobe and hippocampus were performed. The methods used were the polymerase chain reaction (PCR) and sequencing. From the total number of 18 subjects with confirmed Alzheimer's disease and six non-related subjects without histopathological signs of Alzheimer's disease after the age of 90 years, three sequencing changes were found in position 717 of exon 17 of the transmembranous region of the precursor of beta-4 amyloid glycoprotein. In the first case it was substitution of thymin for adenine in codon 717, in the second case substitution of cytosine for thymine, in the third case a sporadic mutation of guanine for thymine in codon 717 was found. Conclusions. It was revealed that codon 717 could be a so-called hot spot site preferred for the preferential development of mutations in codon 717 in the gene for the amyloid precursor protein (APP).

• MeSH
• Alzheimerova nemoc diagnóza   genetika   patologie   MeSH
• amyloidní beta-protein MeSH
• amyloidový prekurzorový protein beta MeSH
• lidé MeSH
• mutace MeSH
• regulační oblast lokusu (genu) MeSH
• Check Tag
• lidé MeSH

The rapid evolution of technologies is a key innovation in the organisation and management of physical activities (PA) and sports. The increase in benefits and opportunities related to the adoption of technologies for both the promotion of a healthy lifestyle and the management of chronic diseases is evident. In the field of telehealth, these devices provide personalised recommendations, workout monitoring and injury prevention. The study aimed to provide an overview of the landscape of technology application to PA organised to promote active lifestyles and improve chronic disease management. This review identified specific areas of focus for the selection of articles: the utilisation of mobile APPs and technological devices for enhancing weight loss, improving cardiovascular health, managing diabetes and cancer and preventing osteoporosis and cognitive decline. A multifactorial intervention delivered via mobile APPs, which integrates PA while managing diet or promoting social interaction, is unquestionably more effective than a singular intervention. The main finding related to promoting PA and a healthy lifestyle through app usage is associated with "behaviour change techniques". Even when individuals stop using the APP, they often maintain the structured or suggested lifestyle habits initially provided by the APP. Various concerns regarding the excessive use of APPs need to be addressed.

• MeSH
• behaviorální terapie MeSH
• cvičení psychologie   MeSH
• dieta MeSH
• lidé MeSH
• mobilní aplikace * MeSH
• telemedicína * MeSH
• životní styl MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

GABAB receptors (GBRs) are key regulators of synaptic release but little is known about trafficking mechanisms that control their presynaptic abundance. We now show that sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs. Of the three interacting proteins, selectively the genetic loss of APP impaired GBR-mediated presynaptic inhibition and axonal GBR expression. Proteomic and functional analyses revealed that APP associates with JIP and calsyntenin proteins that link the APP/GBR complex in cargo vesicles to the axonal trafficking motor. Complex formation with GBRs stabilizes APP at the cell surface and reduces proteolysis of APP to Aβ, a component of senile plaques in Alzheimer's disease patients. Thus, APP/GBR complex formation links presynaptic GBR trafficking to Aβ formation. Our findings support that dysfunctional axonal trafficking and reduced GBR expression in Alzheimer's disease increases Aβ formation.

• MeSH
• amyloid metabolismus   MeSH
• amyloidní beta-protein chemie   metabolismus   MeSH
• axonální transport * MeSH
• axony metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• dendrity metabolismus   MeSH
• epitopy metabolismus   MeSH
• HEK293 buňky MeSH
• kineziny metabolismus   MeSH
• lidé MeSH
• molekuly buněčné adheze chemie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• proteiny nervové tkáně chemie   metabolismus   MeSH
• proteiny vázající GTP metabolismus   MeSH
• proteomika MeSH
• receptory GABA-B metabolismus   MeSH
• sekvence aminokyselin MeSH
• signální transdukce MeSH
• stabilita proteinů MeSH
• synapse metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• hodnocení léčiv MeSH
• plíce účinky léků   MeSH
• psi MeSH
• pyraziny MeSH
• trachea účinky léků   MeSH
• zvířata MeSH
• Check Tag
• psi MeSH
• zvířata MeSH

• Publikační typ
• abstrakt z konference MeSH

BACKGROUND: Prolactin-releasing peptide (PrRP) is a potential drug for the treatment of obesity and associated Type 2 Diabetes Mellitus (T2DM) due to its strong anorexigenic and antidiabetic properties. In our recent study, the lipidized PrRP analog palm11-PrRP31 was proven to exert beneficial effects in APP/PS1 mice, a model of Alzheimer ́s Disease (AD)-like amyloid-β (Aβ) pathology, reducing the Aβ plaque load, microgliosis and astrocytosis in the hippocampus and cortex. OBJECTIVE: In this study, we focused on the neuroprotective and anti-inflammatory effects of palm11-PrRP31 and its possible impact on synaptogenesis in the cerebellum of APP/PS1 mice, because others have suggested that cerebellar Aβ plaques contribute to cognitive deficits in AD. METHODS: APP/PS1 mice were treated subcutaneously with palm11-PrRP31 for 2 months, then immunoblotting and immunohistochemistry were used to quantify pathological markers connected to AD, compared to control mice. RESULTS: In the cerebella of 8 months old APP/PS1 mice, we found widespread Aβ plaques surrounded by activated microglia detected by ionized calcium-binding adapter molecule (Iba1), but no increase in astrocytic marker Glial Fibrillary Acidic Protein (GFAP) compared to controls. Interestingly, no difference in both presynaptic markers syntaxin1A and postsynaptic marker spinophilin was registered between APP/PS1 and control mice. Palm11-PrRP31 treatment significantly reduced the Aβ plaque load and microgliosis in the cerebellum. Furthermore, palm11-PrRP31 increased synaptogenesis and attenuated neuroinflammation and apoptosis in the hippocampus of APP/PS1 mice. CONCLUSION: These results suggest palm11-PrRP31 is a promising agent for the treatment of neurodegenerative disorders.

• MeSH
• Alzheimerova nemoc * metabolismus   MeSH
• amyloidní beta-protein metabolismus   MeSH
• amyloidní plaky patologie   MeSH
• amyloidový prekurzorový protein beta genetika   metabolismus   MeSH
• diabetes mellitus 2. typu * MeSH
• hormon uvolňující prolaktin metabolismus   farmakologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• mozeček MeSH
• myši transgenní MeSH
• myši MeSH
• presenilin-1 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The use of online communities and websites for health information has proliferated along with the use of mobile apps for managing health behaviors such as diet and exercise. The scarce evidence available to date suggests that users of these websites and apps differ in significant ways from non-users but most data come from US- and UK-based populations. In this study, we recruited users of nutrition, weight management, and fitness-oriented websites in the Czech Republic to better understand who uses mobile apps and who does not, including user sociodemographic and psychological profiles. Respondents aged 13-39 provided information on app use through an online survey (n = 669; M age = 24.06, SD = 5.23; 84% female). Among users interested in health topics, respondents using apps for managing nutrition, weight, and fitness (n = 403, 60%) were more often female, reported more frequent smartphone use, and more expert phone skills. In logistic regression models, controlling for sociodemographics, web, and phone activity, mHealth app use was predicted by levels of excessive exercise (OR 1.346, 95% CI 1.061-1.707, p < .01). Among app users, we found differences in types of apps used by gender, age, and weight status. Controlling for sociodemographics and web and phone use, drive for thinness predicted the frequency of use of apps for healthy eating (β = 0.14, p < .05), keeping a diet (β = 0.27, p < .001), and losing weight (β = 0.33, p < .001), whereas excessive exercise predicted the use of apps for keeping a diet (β = 0.18, p < .01), losing weight (β = 0.12, p < .05), and managing sport/exercise (β = 0.28, p < .001). Sensation seeking was negatively associated with the frequency of use of apps for maintaining weight (β = - 0.13, p < .05). These data unveil the user characteristics of mHealth app users from nutrition, weight management, and fitness websites, helping inform subsequent design of mHealth apps and mobile intervention strategies.

• MeSH
• cvičení MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• internet * MeSH
• lidé MeSH
• logistické modely MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mobilní aplikace * MeSH
• osobnost MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• telemedicína * metody   MeSH
• tělesná hmotnost MeSH
• věkové faktory MeSH
• zdravý životní styl * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Primární imunodeficience jsou skupinou čítající v současné době přes 450 onemocnění, jejichž klinický a laboratorní fenotyp je často velmi nespecifický, což představuje zásadní překážku ve vytipování rizikových pacientů, promptní diagnostice a cílené léčbě. V rámci projektu Primary ImmunoDeficiency Look-up App (PIDLA) jsme vytvořili aplikaci napomáhající lékařům v diferenciální diagnostice vrozených poruch imunity. Aplikace je postavena na základech mezinárodní klasifikace primárních imunodeficiencí IUIS z roku 2020 a využívá sofistikovaných vyhledávacích a řadících algoritmů. V textu popisujeme metodu tvorby aplikace a demonstrujeme její funkci. PIDLA je volně dostupný na webové stránce www.pidla.eu.

Primary immunodeficiencies are now a group of over 450 diseases, whose clinical and laboratory phenotypes can be very ambiguous and therefore present a major hurdle to the selection of high-risk patients, quick diagnosis and targetted therapy. As part of the Primary ImmunoDeficiency Look-up App (PIDLA) project we created an app which assists physicians in the differential diagnosis of inborn errors of the immunity. The app is based on the international classification of primary immunodeficiencies IUIS from the year 2020 and utilizes sophisticated searching and ranking algorithms. In this text we describe the method of app development and demonstrate its function. PIDLA is freely available at the webpage www.pidla.eu.

• Klíčová slova
• PIDLA,
• MeSH
• algoritmy MeSH
• diferenciální diagnóza MeSH
• nemoci imunitního systému MeSH
• primární imunodeficience * diagnóza   MeSH
• příznaky a symptomy MeSH
• využití lékařské informatiky * MeSH
• Publikační typ
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

Alzheimer's disease (AD) is a progressive brain disorder characterized by extracellular amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles formed by hyperphosphorylated Tau protein and neuroinflammation. Previous research has shown that obesity and type 2 diabetes mellitus, underlined by insulin resistance (IR), are risk factors for neurodegenerative disorders. In this study, obesity-induced peripheral and central IR and inflammation were studied in relation to AD-like pathology in the brains and periphery of APP/PS1 mice, a model of Aβ pathology, fed a high-fat diet (HFD). APP/PS1 mice and their wild-type controls fed either a standard diet or HFD were characterized at the ages of 3, 6 and 10 months by metabolic parameters related to obesity via mass spectroscopy, nuclear magnetic resonance, immunoblotting and immunohistochemistry to quantify how obesity affected AD pathology. The HFD induced substantial peripheral IR leading to central IR. APP/PS1-fed HFD mice had more pronounced IR, glucose intolerance and liver steatosis than their WT controls. The HFD worsened Aβ pathology in the hippocampi of APP/PS1 mice and significantly supported both peripheral and central inflammation. This study reveals a deleterious effect of obesity-related mild peripheral inflammation and prediabetes on the development of Aβ and Tau pathology and neuroinflammation in APP/PS1 mice.

• MeSH
• Alzheimerova nemoc * etiologie   MeSH
• amyloidní beta-protein MeSH
• diabetes mellitus 2. typu * MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• inzulinová rezistence * MeSH
• myši MeSH
• neurozánětlivé nemoci MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Knowledge of the characteristics of adolescents who use mobile health (mHealth) apps to monitor health and how these characteristics differ from those of app nonusers is limited. OBJECTIVE: We aimed to determine mHealth app use based on adolescent and parental factors, including sociodemographics, digital skills, and health indicators, in a nationally representative sample of Czech adolescents (N=2500). METHODS: Adolescents aged 11 to 16 years and one of their parents participated in an online survey in 2021. A professional research agency recruited the participants. Quotas were used to ensure the sample's representativeness. The sociodemographic factors were the adolescents' age, gender, and parental perceived financial security. The adolescents also provided information about their screen time, eHealth literacy, BMI, health anxiety, physical activity, and sleep quality. Parents reported their digital skills, mobile phone attitudes, and the mediation of their children's online health information-seeking behaviors. We evaluated the differences between the users and nonusers of mHealth apps and identified the significant predictors of mHealth app use. Next, we separately examined how these factors were associated with the use of mHealth apps that track calorie intake or expenditure, number of steps, weight, or sports activity (eg, exercise, running, and working out), as well as other mHealth apps (eg, those that track sleep and heart rate). RESULTS: More than half of the adolescents (1429/2455, 58.21%) reported using mHealth apps. App users were relatively older and, more often, girls. Apps that counted the number of steps were used most frequently, and adolescents whose parents reported higher perceived financial security used them more regularly. Overall, being older and physically active and having higher eHealth literacy skills were associated with using mHealth apps. Adolescents with higher BMI, health anxiety, and lower sleep quality more frequently used mHealth apps to track calorie intake or expenditure, weight, and health indicators. mHealth apps to track physical activity were used more regularly by girls. There was a positive association between parental mediation of online health information-seeking behaviors and adolescents' mHealth app use. CONCLUSIONS: These findings demonstrated that older age, physical activity, and eHealth literacy skills were the common underlying factors of adolescents' mHealth app use. We initially showed parents as significant role models for their children's adoption of, and engagement with, mHealth apps when they actively mediate their online health information-seeking behaviors. Improving the eHealth literacy skills of adolescents through parental guidance might enhance health technology use in this population. Tracking eating behaviors, weight, and health were more prevalent for adolescents who reported higher BMI, health anxiety, and lower sleep quality. Future research studies should examine the determinants and health outcomes of adolescents' mHealth app use longitudinally.

• MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mobilní aplikace * MeSH
• mobilní telefon * MeSH
• průřezové studie MeSH
• rodiče MeSH
• telemedicína * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH