Familial dysautonomia is a debilitating congenital neurodegenerative disorder with no causative therapy. It is caused by a homozygous mutation in ELP1 gene, resulting in the production of the transcript lacking exon 20. The compounds studied as potential treatments include the clinical candidate kinetin, a plant hormone from the cytokinin family. We explored the relationship between the structure of a set of kinetin derivatives (N = 72) and their ability to correct aberrant splicing of the ELP1 gene. Active compounds can be obtained by the substitution of the purine ring with chlorine and fluorine at the C2 atom, with a small alkyl group at the N7 atom, or with diverse groups at the C8 atom. On the other hand, a substitution at the N3 or N9 atoms resulted in a loss of activity. We successfully tested a hypothesis inspired by the remarkable tolerance of the position C8 to substitution, postulating that the imidazole of the purine moiety is not required for the activity. We also evaluated the activity of phytohormones from other families, but none of them corrected ELP1 mRNA aberrant splicing. A panel of in vitro ADME assays, including evaluation of transport across model barriers, stability in plasma and in the presence of liver microsomal fraction as well as plasma protein binding, was used for an initial estimation of the potential bioavailability of the active compounds. Finally, a RNA-seq data suggest that 8-aminokinetin modulates expression spliceosome components.
- MeSH
- kinetin * farmakologie chemie MeSH
- lidé MeSH
- molekulární struktura MeSH
- prekurzory RNA * genetika metabolismus MeSH
- sestřih RNA * účinky léků MeSH
- transkripční elongační faktory metabolismus genetika MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: This research investigated the effects of different hemodialysis modalities combined with low-calcium dialysate (LCD) on mineral metabolism and vascular calcification (VC) in maintenance hemodialysis (MHD) patients with chronic kidney disease (CKD). METHODS: General data were collected from 192 cases of MHD patients, who were divided into 4 groups according to the randomized numerical table. Each group was given LCD treatment, and conventional hemodialysis (HD), high-flux HD (HFHD), hemodiafiltration (HDF), and HD + hemoperfusion (HP) were performed, respectively. The patients were dialyzed 3 times per week for 4 h each time, and each group was treated for 6 months. Fasting venous blood was collected. Serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitive C-reactive protein (hs-CRP) levels were measured by ELISA, calcium (Ca2+), phosphorus (P), Ca2+-P product, serum creatinine (SCr), blood urea nitrogen (BUN), β2 microglobulin (β2-MG), and intact parathyroid hormone (iPTH) were measured by chemiluminescence immunoassay, serum alkaline phosphatase (ALP) was determined by turbidimetric assay, and 25-hydroxyvitamin D (25(OH)D) was measured by autoradiographic immunoassay. To assess the extent of calcification in the iliac artery and abdominal aorta, a multilayer spiral CT device was employed for abdominal scans. RESULTS: Serum IL-6, hs-CRP, TNF-α, Ca2+, P, Ca2+-P product, SCr, BUN, β2-MG, iPTH, and ALP levels decreased, while 25(OH)D levels increased in the four groups after treatment. The most pronounced effect on the reduction of IL-6, hs-CRP, TNF-α, Ca2+, P, Ca2+-P product, SCr, BUN, β2-MG, iPTH, and ALP was in the HD + HP group, followed by the HDF and HFHD groups, and then by the HD group. The rate of VC in the HDF, HFHD, and HD + HP groups was lower than that in the HD group, and the rate in the HD + HP group was lower than that in the HDF and HFHD groups. CONCLUSION: The combination of HD + HP and LCD in treating CKD with MHD is effective, evidently rectifying disruptions in serum Ca2+ and P metabolism, enhancing kidney function, lessening the body's inflammatory response, and lessening VC.
- MeSH
- C-reaktivní protein metabolismus analýza MeSH
- chronická renální insuficience * terapie krev komplikace metabolismus MeSH
- dialýza ledvin * škodlivé účinky MeSH
- dialyzační roztoky farmakologie MeSH
- dospělí MeSH
- fosfor krev MeSH
- interleukin-6 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- minerály metabolismus krev MeSH
- parathormon krev MeSH
- senioři MeSH
- TNF-alfa krev MeSH
- vápník * krev metabolismus MeSH
- vaskulární kalcifikace * krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
This study investigates the interaction of two approved and one newly developed latanoprost formulation with in vitro and in silico models of the tear film and tear film lipid layer (TFLL). Latanoprost, a prostaglandin analogue used for intraocular elevated pressure treatment, is topically delivered by nanocarriers within aqueous solutions or emulsions. The study focuses on the impact of these carriers on drug interactions with the tear film and their effect on the TFLL. Three different types of latanoprost carriers, micellar, nanoemulsion, and polymer-based, were compared, and each revealed distinct interaction patterns with the TFLL. Surface pressure kinetics demonstrated a rapid increase for the benzalkonium chloride formulation and a slow rise for the preservative-free variants. Visualization of the acellular in vitro TFLL model revealed different patterns of incorporation for each formulation, indicating unique interaction mechanisms. Molecular dynamics simulations further revealed different mechanisms of drug release in the TFLL between micellar and nanoemulsion formulations. In-depth examination highlighted the role of triglyceride molecules in replenishing the nonpolar layer of the TFLL, which suggests potential improvements in ocular surface compatibility by adjusting the quality and concentration of the oily phase. These findings suggest the potential for optimizing latanoprost formulations by tuning the oily phase-to-surfactant ratio and selecting suitable surfactants.
- MeSH
- antihypertenziva terapeutické užití MeSH
- glaukom * farmakoterapie MeSH
- latanoprost terapeutické užití MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- nitrooční tlak MeSH
- oči * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Background: Cervical cancer is a preventable disease. The health literacy of women is a significant predictor of behaviour regarding their own health, along with the ability to search for, understand, and use health information, and plays an important role in the use of preventive and screening programmes. Objectives: To evaluate the health literacy level of women of reproductive age in relation to their knowledge of the issue of cervical cancer. Sample: The research sample consisted of women between the ages of 18 and 60 years old (n = 270). Methods: We collected data with the use of a self-constructed questionnaire focused on knowledge about cervical cancer and a standardised health literacy questionnaire (Health Literacy Questionnaire, hereafter the HLQ). Results: In the first five dimensions of the HLQ, the highest achieved score was recorded in the domain "Social support in the field of health" ( = 3.10 ± 0.35). The lowest scores were seen in the domains "Active care of one's own health" ( = 2.91 ± 0.33) and "Assessment of health information" ( = 2.91 ± 0.37). For the last four domains, the lowest score occurred in "Navigation of the health care system" ( = 3.42 ± 0.57), and the highest score was achieved in the domain "Understanding health information to the extent that the individual knows what to do" ( = 3.72 ± 0.45). Respondents assigned to the "sufficiently informed" group achieved a higher average score on the HLQ ( = 29.68 ± 3.13) than respondents assigned to the "insufficiently informed" group ( = 29.28 ± 3.29). Conclusion: It is necessary to increase the effectiveness and adequacy of patient education regarding the importance of passing preventive gynaecological examinations at annual intervals for the prevention of cervical cancer, as well as the possibility of vaccination against HPV.
- MeSH
- časná detekce nádoru metody MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské papilomaviry patogenita MeSH
- nádory děložního čípku * prevence a kontrola MeSH
- primární prevence výchova MeSH
- průzkumy a dotazníky MeSH
- vzdělávání pacientů jako téma MeSH
- zdravotní gramotnost * metody statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Slovenská republika MeSH
Introduction: Patient safety culture is a fundamental aspect of healthcare delivery, profoundly impacted by factors such as teamwork or organizational traits. Research on unfinished nursing care has underscored its importance in relation to patient safety. Objective: To explore the associations between perceived patient safety culture, unfinished nursing care, and the level of teamwork during the clinical placement of nursing students. Methods: A descriptive cross-sectional study was conducted between September and December 2023 using a set of questionnaires comprising the Hospital Survey on Patient Safety Culture for Nursing Students, the Unfinished Nursing Care Survey for Students, and the Nursing Teamwork Survey. The study involved 242 Slovak nursing students. Results: Significant associations were found between nursing students' perceptions of patient safety culture, the level of teamwork, and particular reasons for unfinished nursing care. Four dimensions of patient safety culture predicted the level of teamwork (p < 0.05) and explained 49.1% of the variability in the teamwork perceived during clinical placement. Conclusion: Understanding nursing students' perceptions of patient safety culture and its influencing factors is essential for enhancing the safe provision of nursing care. Future research should continue to explore the dynamic interaction between investigated variables to inform educational and organizational interventions aimed at improving patient care outcomes.
- MeSH
- bezpečnost pacientů * statistika a číselné údaje MeSH
- dospělí MeSH
- klinické praxe metody statistika a číselné údaje MeSH
- lidé MeSH
- ošetřovatelská péče metody MeSH
- ošetřovatelství - vzorové postupy MeSH
- průřezové studie MeSH
- studenti ošetřovatelství * statistika a číselné údaje MeSH
- týmová péče o pacienty statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Slovenská republika MeSH
Introduction: Pediatric palliative care is a specialized form of care provided to children with terminal illnesses or life-threatening conditions. Its aim is not only to control symptoms, but also to improve the overall quality of life of the child and its family. It includes comprehensive support and care that respects the individual needs of the child and its family, including physical, emotional, social, and spiritual aspects. Objective: To translate and implement the language validation of the Pediatric Palliative Care - Parent & Child Needs Survey (PCNeeds) tool and to determine the level of needs of families caring for a child with a life-limiting or life-threatening illness. Methods: To determine the needs of parents of children in palliative care, a quantitative method of a questionnaire survey was used in which 20 parents participated. Data analysis was carried out using descriptive statistics. Results: The highest level of needs of families was in the area of coping with the child's symptoms, including pain. Parents felt emotional strain, social isolation, and overall pressure on the family, including financial burden. However, they also expressed a high degree of satisfaction in many areas, such as communication with health professionals, clarity of information, and the relationship with their child. Conclusion: The study demonstrated the high internal consistency of the Czech version of the PCNeeds measurement instrument. It will be further tested for psychometric properties in the next stage of the research.
This article aims to provide a comprehensive description of the multifaceted influence of dysmenorrhea on women's emotional states and their overall lives, with a focus on both immediate and long-term effects. Immediate impacts include changes in mood and self-perception during menstruation. Changes in self-esteem and identity are among the long-term effects. The research employed a qualitative design involving in-depth interviews with 18 women who have experienced years of painful menstruation. Data were analysed using a combination of thematic analysis (TA) and interpretative phenomenological analysis (IPA), providing a robust framework to understand the nuanced experiences of the participants. Our findings revealed that dysmenorrhea significantly affects emotional states, leading to symptoms of depression and anxiety, heightened emotional reactivity during menstrual periods, and negative effects on self-perception and body image. These emotional disturbances are not only limited to the duration of menstruation but extend beyond this, influencing women's daily lives, relationships, and overall mental health. The study highlights how dysmenorrhea can exacerbate feelings of vulnerability, emotional instability, and social withdrawal, contributing to a persistent negative self-image and compromised self-esteem. Moreover, the chronic nature of dysmenorrhea has been linked to deeper psychological impacts, including a diminished sense of self-efficacy and identity disruption. Women report a pervasive sense of loss of control over their bodies, leading to feelings of helplessness and frustration. These experiences underscore the importance of addressing both the physical and psychological aspects of dysmenorrhea in medical and psychological interventions
- MeSH
- dysmenorea * diagnóza psychologie MeSH
- emoce * MeSH
- kvalita života psychologie MeSH
- lidé MeSH
- nespokojenost s tělem psychologie MeSH
- průzkumy a dotazníky MeSH
- sebepojetí MeSH
- úzkostné poruchy diagnóza etiologie psychologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
