Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.
- MeSH
- Anti-Inflammatory Agents pharmacology chemistry MeSH
- Dexamethasone * pharmacology chemistry analogs & derivatives MeSH
- Liver * drug effects metabolism MeSH
- Polylactic Acid-Polyglycolic Acid Copolymer * chemistry MeSH
- Macrophages * drug effects metabolism MeSH
- Mice MeSH
- Nanospheres * chemistry MeSH
- Drug Carriers chemistry pharmacology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Digital transformation is widely understood as a process where technology is used to modify an organization's products and services and to create new ones. It is rapidly advancing in all sectors of society. Researchers have shown that it is a multidimensional process determined by human decisions based on ideologies, ideas, beliefs, goals, and the ways in which technology is used. In health care and health, the end result of digital transformation is digital health. In this study, a detailed literature review covering 560 research articles published in major journals was performed, followed by an analysis of ideas, beliefs, and goals guiding digital transformation and their possible consequences for privacy, human rights, dignity, and autonomy in health care and health. Results of literature analyses demonstrated that from the point of view of privacy, dignity, and human rights, the current laws, regulations, and system architectures have major weaknesses. One possible model of digital health is based on the dominant ideas and goals of the business world related to the digital economy and neoliberalism, including privatization of health care services, monetization and commodification of health data, and personal responsibility for health. These ideas represent meaningful risks to human rights, privacy, dignity, and autonomy. In this paper, we present an alternative solution for digital health called human-centric digital health (HCDH). Using system thinking and system modeling methods, we developed a system model for HCDH. It uses 5 views (ideas, health data, principles, regulation, and organizational and technical innovations) to align with human rights and values and support dignity, privacy, and autonomy. To make HCDH future proof, extensions to human rights, the adoption of the principle of restricted informational ownership of health data, and the development of new duties, responsibilities, and laws are needed. Finally, we developed a system-oriented, architecture-centric, ontology-based, and policy-driven approach to represent and manage HCDH ecosystems.
- MeSH
- Digital Technology MeSH
- Digital Health * MeSH
- Humans MeSH
- Human Rights MeSH
- Patient-Centered Care * MeSH
- Privacy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Although existing studies have acknowledged the impacts of Hofstede's cultural dimensions on the proactive behaviors of employees or innovations in various contexts, they have not examined the mediating role of proactive behavior between Hofstede's cultural dimensions and entrepreneurial innovativeness. Thus, this study aimed to investigate the mediating impact of proactive behavior between six of Hofstede's cultural dimensions and entrepreneurial innovativeness. Data were collected through standardized surveys from 150 retail entrepreneurs running businesses in China. SPSS and Wrap PLS SEM were used to analyze the data. The findings revealed a positive and significant impact of all six of Hofstede's cultural dimensions, including low power distance, low uncertainty avoidance, long-term orientation, indulgence, collectivism, and masculinity, on proactive behavior among entrepreneurs. Additionally, the mediating influence of proactive behavior was positive and significant for all studied Hofstede cultural dimensions and entrepreneurial innovativeness among entrepreneurs. This study provides important implications for entrepreneurs by emphasizing the importance of proactive behaviors for entrepreneurial innovativeness. Consequently, this study contributes to the existing literature by providing empirical evidence regarding the mediating role of proactive behavior among cultural dimensions and entrepreneurial innovativeness. It suggests that entrepreneurs should exhibit proactive behaviors to implement various innovative practices within their firms.
- MeSH
- Adult MeSH
- Creativity * MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Entrepreneurship * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- China MeSH
Právní praxe
Vydání první xvi, 274 stran ; 23 cm
Publikace se zaměřuje na ochranu osobních údajů v kontextu digitálních technologií. Určeno odborné veřejnosti.; S technickým rozvojem narůstají také možnosti zásahů do soukromí osob a přibývají i jejich nové formy. Zvláště závažnými jsou zásahy ve formě shromažďování a dalšího zpracování řady kategorií osobních údajů, často jde o zpracování hromadná, zpravidla plošného charakteru, dopadající na značná množství osob. Mnohá takováto zpracování jsou uložena obecně závaznými právními předpisy, nejde tak o zásahy samy o sobě protiprávní. Sledovaným účelem takových zpracování osobních údajů je často boj proti terorismu, mnohdy obecněji boj proti trestné činnosti, ale také např. usnadnění a kontrola výběru daní, či jiných dávek a další účely.
- MeSH
- Digital Technology MeSH
- Confidentiality MeSH
- Information Technology MeSH
- Privacy MeSH
- Legislation as Topic MeSH
- Publication type
- Monograph MeSH
- Geographicals
- Czech Republic MeSH
- Europe MeSH
- Conspectus
- Ústavní právo. Správní právo
- NML Fields
- lidská práva
Právní monografie
Vydání první xi, 131 stran ; 24 cm
Publikace se zaměřuje na právo a ochranu osobních údajů a soukromí v rámci informačních technologií. Určeno odborné veřejnosti.; Rozbor české a unijní právní regulace ochrany soukromí a osobních údajů v elektronických komunikacích na základě stavu k 12. 12. 2024.
- MeSH
- Information Technology MeSH
- Wearable Electronic Devices MeSH
- Personal Autonomy MeSH
- Personally Identifiable Information MeSH
- Privacy MeSH
- Legislation as Topic MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Ústavní právo. Správní právo
- NML Fields
- lidská práva
Differences in survival according to the pTERT mutation subtypes (-124C > T, -146C > T, and tandem -138_139CC > TT) have been observed. The present study aimed to describe the clinical as the histopathological and molecular cutaneous melanoma features according to the presence of the three most prevalent pTERT mutation subtypes (-124C > T, -146C > T, and tandem -138_139CC > TT). A retrospective cross-sectional study including 684 patients was designed, and a Partial Least-Squares Discriminant Analysis (PLS-DA) was performed. After the PSL-DA, it was observed that the tandem -138_139CC > TT subtype differs from the other subtypes. The model demonstrated that the -124C > T and the -138_139 CC > TT subtypes were associated with fast-growing melanomas (OR 0.5, CI 0.29-0.86, p = .012) and with Breslow >2 mm (OR 0.6, CI 0.37-0.97, p = .037), compared to the -146C > T mutation. Finally, the -124C > T appeared to be more associated with the presence of TILs (non-brisk) than the -146C > T (OR 0.6, CI 0.40-1.01, p = .05). These findings confirmed that the -124C > T and the tandem -138_139 CC > TT subtypes are both highly associated with the presence of features of aggressiveness; however, only the -124C > T was highly associated with TILs. This difference could explain the worse survival rate associated with the tandem -138_139CC > TT mutations.
- MeSH
- Humans MeSH
- Melanoma * genetics pathology mortality MeSH
- Mutation MeSH
- Skin Neoplasms genetics pathology mortality MeSH
- Promoter Regions, Genetic * genetics MeSH
- Cross-Sectional Studies MeSH
- Retrospective Studies MeSH
- Telomerase * genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Several muscle variations have been observed in flexor aspect of forearm which can hamper normal functioning of hand or may remain silent. One such unreported variation has been described in this report. An accessory muscle in the left forearm was found involving flexor carpi ulnaris (FCU) and palmaris longus (PL). This muscle was originating from the distal part of both FCU and PL through a slip from each tendon. After merging, it passed above the ulnar nerve and artery in the roof of Guyon's canal. This type of variation can cause neurovascular compression and can also mimic soft tissue mass, tumour or neuroma and can be misdiagnosed. Knowledge about this type of variation is important in cases of neurovascular decompression, forearm, and hand surgeries and these can be utilized in tendon transfer or free muscle flap for reconstruction purposes.
- MeSH
- Anatomic Variation MeSH
- Adult MeSH
- Muscle, Skeletal * abnormalities MeSH
- Humans MeSH
- Forearm * abnormalities MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
The purpose of this study was to determine the effects of resistance training (RT) alongside creatine-hydrochloride (Cr-HCl) or creatine monohydrate (CrM) supplementation on anabolic/catabolic hormones, strength, and body composition. Forty participants with an age range of 18-25 years were randomly divided into four groups (n=10): RT+Cr-HCl (0.03 g.kg-1 of body mass), RT+CrM-loading phase (CrM-LP) (0.3 g.kg-1 of body mass for five days (loading) and 0.03 g.kg-1 body mass for 51 days (maintenance)), RT+CrM-without loading phase (CrM-WLP) (0.03 g.kg-1 body mass), and RT+placebo (PL). The participants consumed supplements and performed RT with an intensity of 70-85 % 1RM for eight weeks. Before and after the training and supplementation period, strength (1RM), body composition (percent body fat (PBF), skeletal muscle mass (SMM), muscular cross-sectional area (MCSA)) and serum levels of testosterone, growth hormone (GH), insulin-like growth factor-1 (IGF-1), cortisol, adrenocorticotropic hormone (ACTH), follistatin and myostatin were measured. The results showed that in the supplementation groups, strength, arm and thigh MCSA, and SMM significantly increased, and PBF significantly decreased (P=0.05); this change was significant compared to the PL group (P=0.05). In addition, the results showed a significant increase in GH, IGF-1 levels, the ratio of follistatin/myostatin, testosterone/cortisol (P=0.05), and a significant decrease in cortisol and ACTH levels (P=0.05) in the supplementation groups. Hormonal changes in GH, IGF-1, testosterone/cortisol, cortisol, and ACTH levels in the supplementation groups were significant compared to the PL group (P=0.05). The results showed that CrM and Cr-HCl significantly enhanced the beneficial effects of RT on strength, hypertrophy, and hormonal responses, with Cr-HCl showing no benefit over CrM.
- MeSH
- Adult MeSH
- Hydrocortisone blood MeSH
- Insulin-Like Growth Factor I metabolism MeSH
- Muscle, Skeletal metabolism drug effects MeSH
- Creatine * MeSH
- Humans MeSH
- Human Growth Hormone blood MeSH
- Adolescent MeSH
- Young Adult MeSH
- Resistance Training * methods MeSH
- Dietary Supplements * MeSH
- Body Composition * MeSH
- Muscle Strength * drug effects MeSH
- Testosterone blood MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
Although the identification of animal species and muscles have been reported previously, no studies have been found on the use of NIR spectroscopy to identify individual animals from the analysis of commercial meat cuts. The aim of this study was to evaluate the use of a portable near infrared (NIR) instrument combined with classical chemometrics methods [principal component analysis (PCA) and partial least squares discriminant analysis PLS-DA)] to identify the origin of individual goat animals using the spectral signature of their commercial cut. Samples were collected from several carcasses (6 commercial cuts x 24 animals) sourced from a commercial abattoir in Queensland (Australia). The NIR spectra of the samples were collected using a portable NIR instrument in the wavelength range between 950 and 1600 nm. Overall, the PLS-DA models correctly classify 82% and 79% of the individual goat samples using either the goat rack or loin cut samples, respectively. The study demonstrated that NIR spectroscopy was able to identify individual goat animals based on the spectra properties of some of the commercial cut samples analysed (e.g. loin and rack). These results showed the potential of this technique to identify individual animals as an alternative to other laboratory methods and techniques commonly used in meat traceability.
- Publication type
- Journal Article MeSH
1. elektronické vydání 1 online zdroj (152 stran)
Čarodějnická dvojčata Bela a Dona se zúčastní spolu s ostatními studenty školy pro nadpřirozené bytosti plesu základní školy. Ale nesmí se před obyčejnými lidmi prozradit, takže jsou vyloučena jakákoliv kouzla. Jak to asi všichni zvládnou? Vtipný příběh o malých čarodějkách, velkém kamarádství a trampotách strašidel ve světě lidí.