335 research outputs found
Supplemental Material - Waist circumference and cardiometabolic parameters in people of African/Caribbean ancestry with HIV in South London (CKD-AFRICA study)
No full textSupplemental Material for Waist circumference and cardiometabolic parameters in people of African/Caribbean ancestry with HIV in South London (CKD-AFRICA study) by Laura Cechin, Lourdez Dominguez-Dominguez, Lucy Campbell, Lisa Hamzah, Julie Fox, Royce P Vincent, Georgios K Dimitriadis, Louise Goff and Frank A Post in International Journal of STD & AIDS.</p
K2 observations of SN 2018oh reveal a two-component rising light curve for a Type Ia supernova
No full textWe present an exquisite 30 minute cadence Kepler (K2) light curve of the Type Ia supernova (SN Ia) 2018oh (ASASSN-18bt), starting weeks before explosion, covering the moment of explosion and the subsequent rise, and continuing past peak brightness. These data are supplemented by multi-color Panoramic Survey Telescope (Pan-STARRS1) and Rapid Response System 1 and Cerro Tololo Inter-American Observatory 4 m Dark Energy Camera (CTIO 4-m DECam) observations obtained within hours of explosion. The K2 light curve has an unusual two-component shape, where the flux rises with a steep linear gradient for the first few days, followed by a quadratic rise as seen for typical supernovae (SNe) Ia. This "flux excess" relative to canonical SN Ia behavior is confirmed in our i-band light curve, and furthermore, SN 2018oh is especially blue during the early epochs. The flux excess peaks 2.14 ± 0.04 days after explosion, has a FWHM of 3.12 ± 0.04 days, a blackbody temperature of K, a peak luminosity of , and a total integrated energy of . We compare SN 2018oh to several models that may provide additional heating at early times, including collision with a companion and a shallow concentration of radioactive nickel. While all of these models generally reproduce the early K2 light curve shape, we slightly favor a companion interaction, at a distance of ~ based on our early color measurements, although the exact distance depends on the uncertain viewing angle. Additional confirmation of a companion interaction in future modeling and observations of SN 2018oh would provide strong support for a single-degenerate progenitor system
Multiple electrolyte disturbances as the presenting feature of Multiple Endocrine Neoplasia Type 1 (MEN-1)
No full textA 49-year-old teacher presented to his GP with lethargy and lower limb weakness. He had noticed polydipsia, polyuria and had experienced weight loss, albeit with an increase in central adiposity. He had no concomitant illnesses and took no regular medications. He had hypercalcaemia (adjusted calcium: 3.34mmol/L) with hyperparathyroidism (PTH: 356ng/L) and hypokalaemia (K: 2.7mmol/L) and was admitted for intravenous potassium replacement. A contrast-enhanced CT Chest/Abdomen/Pelvis scan revealed a well-encapsulated anterior mediastinal mass measuring 17cm x 11cm with central necrosis, compressing rather than invading adjacent structures. A neck ultrasound revealed a 2cm right inferior parathyroid lesion. On review of CT imaging, the adrenals appeared normal, but a pancreatic lesion was noted adjacent to the uncinate process,His serum cortisol was 2612 nmol/L, and ACTH was elevated at 67ng/L, followed by inadequate cortisol suppression to 575nmol/L from an overnight dexamethasone suppression test (ONDST). His pituitary MRI was normal, with unremarkable remaining anterior pituitary biochemistry. His admission was further complicated by increased urine output to 10L/24hrs and despite three precipitating factors for the development of diabetes insipidus including hypercalcaemia, hypokalaemia and hypercortisolaemia, due to academic interest, a water deprivation test was conducted. An 18FDG-PET scan demonstrated high avidity of the mediastinal mass with additionally active bilateral superior mediastinal nodes. The pancreatic lesion was not FDG avid. On 68Ga DOTATE-PET scan, the mediastinal mass was moderately avid, and the 32mm pancreatic urcinate process mass showed significant uptake. Genetic testing confirmed Multiple Endocrine Neoplasia Type 1 (MEN-1).<br/
Effect of selected imidazolium ionic liquids on the permeability of human skin during their co-application with model compounds
Get PDFUniverzita Karlova, Farmaceutická fakulta v Hradci Králové Katedra Farmaceutické technologie Školitel: Dr. Georgios Paraskevopoulos, Ph.D. Autor: Denisa Trávníčková Název diplomové práce: Vliv vybraných imidazoliových iontových kapalin na permeabilitu lidské kůže při jejich ko-aplikaci s modelovými sloučeninami Transdermální aplikace je vzhledem ke snadné aplikaci, vyhnutí se first - pass efektu a velkému povrchu kůže vhodná cesta podání léčivé látky. Hlavní bariérou, která omezuje přístup většiny látek do hlubších vrstev kůže a do systémové cirkulace je stratum corneum. Permeaci léčiv kůži navíc ovlivňuje řada faktorů, zejména fyzikálně-chemické vlastnosti látky. Struktura a funkce SC je zásadní pro udržení kožní bariéry a nalézt způsob k překonání bariérových vlastností kůže, který by nepoškodil kůži, je obtížné. Použití iontových kapalin jako enhancerů kožní penetrace představuje nový směr ve vývoji dermatologických a farmaceutických přípravků. Struktura iontových kapalin umožňuje nespočetnou kombinaci kationtů a aniontů, které by teoreticky mohly vést k syntéze iontových kapalin s požadovanou vlastností či aplikací. Tato práce přispívá k pochopení vlivu dvou imidazolových iontových kapalin na permeační profil modelových látek - theofylinu a sodné soli diklofenaku, při aplikaci na lidskou kůži...Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Author: Denisa Trávníčková Title of the thesis: Effect of selected imidazolium ionic liquids on the permeability of human skin during their co-application with model compounds Transdermal application is due to the ease of application, avoiding the first-pass effect and the large surface area of the skin make it a suitable route of administration. The stratum corneum is the main barrier that limits the access of most substances to the deeper layers of the skin and to the systemic circulation. In addition, the permeation of drugs through the skin is influenced by a number of factors, particularly the physicochemical properties of the substance. The structure and function of the SC is critical to the maintenance of the skin barrier, and finding a way to overcome the barrier properties of the skin that does not damage the skin is difficult. The use of ionic liquids as skin penetration enhancers represents a new direction in the development of dermatological and pharmaceutical products. The structure of ionic liquids allows for a myriad of combinations of cations and anions that could theoretically lead to the synthesis of ionic liquids with desired properties...Department of Pharmaceutical TechnologyKatedra farmaceutické technologieFarmaceutická fakulta v Hradci KrálovéFaculty of Pharmacy in Hradec Králov
Intensifiers
No full textThe label ‘intensifiers’ (or ‘emphatics’) groups together words, widely attested crosslinguistically (e.g. Eng. x-self, Germ. selbst, Ital. stesso, Lat. ipse, Japanese zisin and zibun, Mandarin zı j ĭetc.), whose main function is to signal some sort of emphasis or focus with respect to a nominal head they are adjoined to in the sentence, as in The author herself will present the book. In addition to the term ‘intensifiers’
(Moravcsik 1972; Edmondson and Plank 1978), there exist many other labels in the relevant literature to define this sub-class of functional words, which reflect the (anything but closed) debate on their actual categorial status. This entry discuss the origin and the function of the prototypical Ancient Greek intensifier, autós, which is classified among (demonstrative) pronouns
Syntéza fluorovaných derivátů serinu a studium jejich vlivu na bariérovou funkci kůže
No full textCharles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Supervisor: Prof. PharmDr. Kateřina Vávrová, Ph.D. Consultant: Dr. Georgios Paraskevopoulos, Ph.D. Author: Richard Župina Title of the thesis: Synthesis of fluorinated serine derivatives and study of their effect on skin barrier function The human skin serves as a barrier against physical, chemical and microbial injury. When the skin barrier is perturbed, there is a possibility of microbial infiltration and biochemical damage. Ceramides, as essential components of the skin lipid layer, help to maintain the barrier integrity. Decreased content of skin ceramides in epidermis is connected with skin diseases such as atopic dermatitis and psoriasis. Previous findings of our research group proved that a ceramide analogue with similar steric and hydrophobic parameters to skin ceramides could selectively supplement the recovery of perturbed human skin barrier. The goal of this study was to design a convenient synthesis of ceramide analogues derived from L-serine with two long aliphatic chains. The first chain is amidically bound lignoceric acid and the second chain is either a 10 or a 14 carbon polyfluorinated chain conjugated with the rest of the molecule by an ester bond. Furthermore, the aim of this...Univerzita Karlova, Farmaceutická fakulta v Hradci Králové Katedra Organické a Bioorganické Chemie Školitel: Prof. PharmDr. Kateřina Vávrová, Ph.D. Konzultant: Dr. Georgios Paraskevopoulos, Ph.D. Autor: Richard Župina Název diplomové práce: Syntéza fluorovaných derivátov serínu a štúdium ich vplyvu na bariérovú funkciu kože Ľudská koža slúži ako bariéra proti fyzickému, chemickému a mikrobiálnemu poškodeniu. Ak je kožná bariéra narušená, dochádza k možnosti infiltrácie mikróbov a biochemického poškodenia. Ceramidy slúžia ako základné zložky lipidovej vrstvy pokožky, čím napomáhajú udržiavať integritu kožnej bariéry. Znížený obsah epidermálnych ceramidov súvisí s kožnými ochoreniami, ako je atopická dermatitída a psoriáza. Predchádzajúce zistenia našej výskumnej skupiny preukázali, že molekula analogická k ceramidom nachádzajúcim sa v epiderme, ktorá má podobné sterické a hydrofóbne vlastnosti, by mohla suplementovať nedostatok ceramidov v stratum corneum jednoduchým fyzikálno-chemickým pôsobením. Cieľom tejto štúdie bolo navrhnúť jednoduchú syntézu molekúl analogických ku kožným ceramidom vychádzajúcich zo štruktúry L-serínu s dvoma dlhými alifatickými reťazcami. Prvý reťazec pochádza z kyseliny lignocerovej viazanej amidovou väzbou k zbytku molekuly a druhý reťazec je buď 10 alebo 14 uhlíkový...Department of Organic And Bioorganic ChemistryKatedra organické a bioorganické chemieFarmaceutická fakulta v Hradci KrálovéFaculty of Pharmacy in Hradec Králov
Syntéza fluorovaných derivátů serinu a studium jejich vlivu na bariérovou funkci kůže
No full textCharles University, Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Supervisor: Prof. PharmDr. Kateřina Vávrová, Ph.D. Consultant: Dr. Georgios Paraskevopoulos, Ph.D. Author: Richard Župina Title of the thesis: Synthesis of fluorinated serine derivatives and study of their effect on skin barrier function The human skin serves as a barrier against physical, chemical and microbial injury. When the skin barrier is perturbed, there is a possibility of microbial infiltration and biochemical damage. Ceramides, as essential components of the skin lipid layer, help to maintain the barrier integrity. Decreased content of skin ceramides in epidermis is connected with skin diseases such as atopic dermatitis and psoriasis. Previous findings of our research group proved that a ceramide analogue with similar steric and hydrophobic parameters to skin ceramides could selectively supplement the recovery of perturbed human skin barrier. The goal of this study was to design a convenient synthesis of ceramide analogues derived from L-serine with two long aliphatic chains. The first chain is amidically bound lignoceric acid and the second chain is either a 10 or a 14 carbon polyfluorinated chain conjugated with the rest of the molecule by an ester bond. Furthermore, the aim of this...Univerzita Karlova, Farmaceutická fakulta v Hradci Králové Katedra Organické a Bioorganické Chemie Školitel: Prof. PharmDr. Kateřina Vávrová, Ph.D. Konzultant: Dr. Georgios Paraskevopoulos, Ph.D. Autor: Richard Župina Název diplomové práce: Syntéza fluorovaných derivátov serínu a štúdium ich vplyvu na bariérovú funkciu kože Ľudská koža slúži ako bariéra proti fyzickému, chemickému a mikrobiálnemu poškodeniu. Ak je kožná bariéra narušená, dochádza k možnosti infiltrácie mikróbov a biochemického poškodenia. Ceramidy slúžia ako základné zložky lipidovej vrstvy pokožky, čím napomáhajú udržiavať integritu kožnej bariéry. Znížený obsah epidermálnych ceramidov súvisí s kožnými ochoreniami, ako je atopická dermatitída a psoriáza. Predchádzajúce zistenia našej výskumnej skupiny preukázali, že molekula analogická k ceramidom nachádzajúcim sa v epiderme, ktorá má podobné sterické a hydrofóbne vlastnosti, by mohla suplementovať nedostatok ceramidov v stratum corneum jednoduchým fyzikálno-chemickým pôsobením. Cieľom tejto štúdie bolo navrhnúť jednoduchú syntézu molekúl analogických ku kožným ceramidom vychádzajúcich zo štruktúry L-serínu s dvoma dlhými alifatickými reťazcami. Prvý reťazec pochádza z kyseliny lignocerovej viazanej amidovou väzbou k zbytku molekuly a druhý reťazec je buď 10 alebo 14 uhlíkový...Katedra organické a bioorganické chemieDepartment of Organic And Bioorganic ChemistryFarmaceutická fakulta v Hradci KrálovéFaculty of Pharmacy in Hradec Králov
Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY):a randomised, controlled, open-label, platform trial and updated meta-analysis
Get PDFBACKGROUND: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1-2 inhibitor, for the treatment of patients admitted to hospital with COVID-19.METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing.FINDINGS: Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45-0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72-0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes.INTERPRETATION: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth.FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.</p
Molnupiravir or nirmatrelvir-ritonavir plus usual care versus usual care alone in patients admitted to hospital with COVID-19 (RECOVERY):a randomised, controlled, open-label, platform trial
No full textAdvancements in pharmacological and surgical interventions for the management of obesity and related cardiometabolic and reproductive sequelae
No full textThis thesis presents work from eight papers on cardiometabolic and gonadal effects of medical/pharmacological and surgical interventions for the management of obesity and associated states of dysmetabolism.
The key principle explored in this thesis is that obesity is not simply a psycho-social issue associated with lack of will power but rather a complex, multifactorial, relapsing disease causing a plethora of comorbid conditions. Emphasis is given on the cardiometabolic and reproductive sequelae, and recent advancements in their aetiology and management.
The fundamental basis for advanced management of obesity with pharmacotherapy or bariatric surgery for the purpose of accomplishing weight loss is the determination that complications of complex obesity can be reversed or down-staged by successful weight loss in patients who have been unable to sustain weight loss by universal interventions including behavioural and lifestyle programmes. Failure of lifestyle/behavioural interventions to accomplish sustained weight loss is common among people with severe and complex obesity. The biological drivers involved in the limitations associated with maintaining weight loss are powerful.
My three papers on bariatric surgery and five papers on pharmacological interventions highlight the unmet need for additional personalised therapeutic options for the management of obesity and emphasise on the role of these interventions in the management of cardiometabolic and reproductive complications of the disease we call obesity
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