Natural history of KBG syndrome in a large European cohort

KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: -0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11.</p

Development Policy of the European Union towards Least Developed Countries

Hlavním cílem této práce je představení rozvojové politiky Evropské unie vůči nejméně rozvinutým zemím světa (LDCs), a to na pozadí dvou vybraných členských států - Velké Británie a Německa. Práce je rozčleněna do několika kapitol. První kapitola se věnuje vývoji teoretického přístupu k rozvoji v rámci EU již od vzniku EHS roku 1958. Druhá část se poté soustředí na rozvojovou politiku EU od roku 2000, a to zejména na nejdůležitější dokumenty a iniciativy zaměřené na kategorii LDCs. V rámci této kapitoly je rovněž prezentován samotný koncept nejméně rozvinutých zemí, jak ho ustanovila OSN roku 1971. Následující kapitoly jsou již empiricko-analytickou částí práce a je zde provedena analýza rozvojových politik vybraných zemí vůči kategorii LDCs na základě určených kritérií. Výzkum je zaměřen například na hlavní cíle spolupráce, prioritní sektory či využívané nástroje.ObhájenoThe main aim of this thesis is to present development policy of the European Union towards Least Developed Countries. I decided to analyze and compare two members of the EU, the United Kingdom and Germany. The thesis is divided into several chapters. The first chapter focuses on the evolution of theoretical approach to development inside the EU since the foundation of the EEC in 1958. The second part then follows up the current development policy of the EU. Main strategies and documents of the EU towards LDCs are presented in this chapter. Also the concept of LDCs made by the UN in 1971 is defined here. The following chapters represent the practical part of the thesis. These chapters are based on the analysis of the development policy of the selected countries towards LDCs. The analysis is based on certain criterions, such as main goals of the policies or priority sectors

The United Kingdom and Scotland - the perspectives of the independence

Tato práce analyzuje výzvy, kterým by muselo čelit Skotsko, pokud by se rozhodlo vyhlásit nezávislost na Velké Británii. Protože se skotské představy o struktuře nezávislého skotského státu značně liší od těch britských, Holyrood by čekala mnohá vyjednávání jak v oblasti ekonomické, tak politické. Práce se rovněž věnuje případnému mezinárodnímu postavení nezávislého Skotska a jeho členství v organizacích působících na evropském kontinentě.ObhájenoThis thesis aims to analyse the challenges that Scotland would have to face, if it will decide to declare independence from the United Kingdom. Because scottish ideas about the structure of the independent scottish state are quite different than those of british, Holyrood would have to go through many negotiations in economic and political sphere. The thesis also focuses on potentional international status of Scotland and its membership in organizations operating on the european continent

Development Policy of the European Union towards Least Developed Countries

Hlavním cílem této práce je představení rozvojové politiky Evropské unie vůči nejméně rozvinutým zemím světa (LDCs), a to na pozadí dvou vybraných členských států - Velké Británie a Německa. Práce je rozčleněna do několika kapitol. První kapitola se věnuje vývoji teoretického přístupu k rozvoji v rámci EU již od vzniku EHS roku 1958. Druhá část se poté soustředí na rozvojovou politiku EU od roku 2000, a to zejména na nejdůležitější dokumenty a iniciativy zaměřené na kategorii LDCs. V rámci této kapitoly je rovněž prezentován samotný koncept nejméně rozvinutých zemí, jak ho ustanovila OSN roku 1971. Následující kapitoly jsou již empiricko-analytickou částí práce a je zde provedena analýza rozvojových politik vybraných zemí vůči kategorii LDCs na základě určených kritérií. Výzkum je zaměřen například na hlavní cíle spolupráce, prioritní sektory či využívané nástroje.ObhájenoThe main aim of this thesis is to present development policy of the European Union towards Least Developed Countries. I decided to analyze and compare two members of the EU, the United Kingdom and Germany. The thesis is divided into several chapters. The first chapter focuses on the evolution of theoretical approach to development inside the EU since the foundation of the EEC in 1958. The second part then follows up the current development policy of the EU. Main strategies and documents of the EU towards LDCs are presented in this chapter. Also the concept of LDCs made by the UN in 1971 is defined here. The following chapters represent the practical part of the thesis. These chapters are based on the analysis of the development policy of the selected countries towards LDCs. The analysis is based on certain criterions, such as main goals of the policies or priority sectors

A place as a response of a Gothic novel in a Czech scary story of the 18th and 19th centuries

Bakalářská práce se zabývá funkcí a významu místa v gotického románu zkoumaném v českých strašidelných povídkách 18. a 19. století. Zabývá se funkcí a proměny míst zámku, hradu, věže, přírody, domu, domova a pokoje. Zkoumané texty pocházejí především z antologie Mrtví tanečníci a Zazděná slečna a jiné příhody pro vyprávění. Úvodní teoretická část představuje literární žánr gotického románu z mnoha aspektů. Vysvětluje jeho vývoj a rozvoj ve světě. Praktická část se věnuje zkoumání funkce místa ve strašidelných povídkách 18. a 19. století. Tvrzení doprovázejí náležité příklady.The bachelor's thesis occupy with the function and meaning of the place in the Gothic novel research in Czech scary stories of the 18th and 19th centuries. The thesis pursue the function and transformation of the places of the chateau, castle, tower, nature, house, home and room. The researched texts are mainly from the anthologies Mrtví tanečníci and Zazděná slečna a jiné příběhy pro vyprávění. The introductory theoretical part presents the literary genre of the Gothic novel from many perspectives. The thesis explains development and expansion of Gothic novels round the world. The practical part apply with the investigation of the function of the place in scary stories of the 18th and 19th centuries. My statements are confirmed by appropriate examples.Fakulta filozofickáStudentka představila téma príce, cíle, zvolenou metodu. Vedoucí a oponent práce seznámili komisi s posudky. Studentka reagovala na dotazy obsažené v posudcích a na další dotazy členů komise. Diskuse.Dokončená práce s úspěšnou obhajobo

Aging and high-fat diet feeding lead to peripheral insulin resistance and sexdependent changes in brain of mouse model of tau pathology THY-Tau22

Background Obesity leads to low-grade inflammation in the adipose tissue and liver and neuroinflammation in the brain. Obesity-induced insulin resistance (IR) and neuroinflammation seem to intensify neurodegeneration including Alzheimer's disease. In this study, the impact of high-fat (HF) diet-induced obesity on potential neuroinflammation and peripheral IR was tested separately in males and females of THY-Tau22 mice, a model of tau pathology expressing mutated human tau protein. Methods Three-, 7-, and 11-month-old THY-Tau22 and wild-type males and females were tested for mobility, anxiety-like behavior, and short-term spatial memory in open-field and Y-maze tests. Plasma insulin, free fatty acid, cholesterol, and leptin were evaluated with commercial assays. Liver was stained with hematoxylin and eosin for histology. Brain sections were 3 ',3 '-diaminobenzidine (DAB) and/or fluorescently detected for ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and tau phosphorylated at T231 (pTau (T231)), and analyzed. Insulin signaling cascade, pTau, extracellular signal-regulated kinase 1/2 (ERK1/2), and protein phosphatase 2A (PP2A) were quantified by western blotting of hippocampi of 11-month-old mice. Data are mean +/- SEM and were subjected to Mann-Whitney t test within age and sex and mixed-effects analysis and Bonferroni's post hoc test for age comparison. Results Increased age most potently decreased mobility and increased anxiety in all mice. THY-Tau22 males showed impaired short-term spatial memory. HF diet increased body, fat, and liver weights and peripheral IR. HF diet-fed THY-Tau22 males showed massive Iba1+ microgliosis and GFAP+ astrocytosis in the hippocampus and amygdala. Activated astrocytes colocalized with pTau (T231) in THY-Tau22, although no significant difference in hippocampal tau phosphorylation was observed between 11-month-old HF and standard diet-fed THY-Tau22 mice. Eleven-month-old THY-Tau22 females, but not males, on both diets showed decreased synaptic and postsynaptic plasticity. Conclusions Significant sex differences in neurodegenerative signs were found in THY-Tau22. Impaired short-term spatial memory was observed in 11-month-old THY-tau22 males but not females, which corresponded to increased neuroinflammation colocalized with pTau(T231) in the hippocampi and amygdalae of THY-Tau22 males. A robust decrease in synaptic and postsynaptic plasticity was observed in 11-month-old females but not males. HF diet caused peripheral but not central IR in mice of both sexes

The Use of Medical Grade Honey on Infected Chronic Diabetic Foot Ulcers—A Prospective Case-Control Study

Non-healing wounds are usually colonised and contaminated by different types of bacteria. An alternative to antibiotic treatment in patients with infected wounds with local signs of inflammation may be medical grade honey (MGH). MGH has antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory features. This study aims to evaluate the effect of MGH therapy on infected non-healing wounds, especially for diabetic foot syndrome. Prospective, observational case series (n = 5) of patients with wounds of diabetic foot syndrome are presented. There were five males with an average age of 61.6 years. All wounds were treated with MGH, and the healing trajectory was rigorously and objectively monitored. In all cases, there was a gradual disappearance of odour, pain, and exudation. Moreover, the wound areas significantly reduced within 40 days and there was a decrease in glycated haemoglobin and glycaemia values. All these outcomes resulted in improved quality of life of the patients. Despite bacterial colonisation, antibiotic treatment was not necessary. All wounds were completely healed. MGH has antimicrobial, anti-inflammatory, and antioxidant effects in diabetic foot syndrome wounds, does not increase glycated haemoglobin or glycaemia levels, and thus constitutes an effective alternative to the use of antibiotics in the treatment of locally infected wounds

Release of Terpenes from Fir Wood during Its Long-Term Use and in Thermal Treatment

Building structures made from fir wood are often attacked by wood-destroying insects for which the terpenes it contains serve as attractants. One of the possibilities for extending the lifetime of structures is to use older wood with a lower content of terpenes and/or thermally modified wood. The study evaluated the levels of terpenes in naturally aged fir wood (108, 146, 279, 287 and 390 years) and their decrease by thermal treatment (the temperature of 60 °C and 120 °C, treatment duration of 10 h). Terpenes were extracted from wood samples by hexane and analyzed by gas-chromatography mass-spectrometry (GC-MS). The results indicate that recent fir wood contained approximately 60 times more terpenes than the oldest wood (186:3.1 mg/kg). The thermal wood treatment speeded up the release of terpenes. The temperature of 60 °C caused a loss in terpenes in the recent fir wood by 62%, the temperature of 120 °C even by &gt;99%. After the treatment at the temperature of 60 °C the recent fir wood had approximately the same quantity of terpenes as non-thermally treated 108 year old wood, &lt;em&gt;i.e.&lt;/em&gt;, approximately 60–70 mg/kg. After the thermal treatment at the temperature of 120 °C the quantity of terpenes dropped in the recent as well as the old fir wood to minimum quantities (0.7–1.1 mg/kg). The thermal treatment can thus be used as a suitable method for the protection of fir wood from wood-destroying insects

Novel Lipidized Analog of Prolactin-Releasing Peptide Improves Memory Impairment and Attenuates Hyperphosphorylation of Tau Protein in a Mouse Model of Tauopathy

International audienc

Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity.

Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus. Two-week treatment with analogs that were palmitoylated through linkers to Lys11 (analogs 1 and 2), but not with analog modified both at the N-terminus and Lys11 (analog 3) decreased body and liver weights, insulin, leptin, triglyceride, cholesterol and free fatty acid plasma levels in a mouse model of diet-induced obesity. Moreover, the expression of uncoupling protein-1 was increased in brown fat suggesting an increase in energy expenditure. In addition, treatment with analogs 1 and 2 but not analog 3 significantly decreased urinary concentrations of 1-methylnicotinamide and its oxidation products N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide, as shown by NMR-based metabolomics. This observation confirmed the previously reported increase in nicotinamide derivatives in obesity and type 2 diabetes mellitus and the effectiveness of analogs 1 and 2 in the treatment of these disorders