BACKGROUND: Ring 18 chromosome is a rare chromosomal aberration associated with a wide range of symptoms affecting all organ systems. One possible symptom associated with this condition is an orofacial cleft. However, to date, there are very few reported cases where the cleft has been surgically treated. CASE DESCRIPTION: In our case study, we present a female patient with Ring 18 chromosome who underwent cleft palate surgery at 14 months of age. Subsequently, a reoperation of the palate was necessary due to wound dehiscence. For the secondary reconstruction of the palate, the acellular dermal matrix (ADM) MatriDerm® was used to improve healing. The cleft palate surgery progressively improved her ability to take in food, allowing a transition from nasogastric tube feeding to oral intake. RESULTS: This is only the fourth reported case of a child with Ring 18 chromosome undergoing surgical correction of an orofacial cleft. Additionally, it is one of the first cases where an ADM MatriDerm® was used in the surgical correction of a cleft palate. In this study, we also present a comprehensive literature review, providing an overview of the various symptoms associated with this syndrome. CONCLUSION: Cleft palate surgery had a very positive effect on improving food intake in the patient with Ring 18 chromosome. The use of an acellular dermal matrix during the secondary cleft palate surgery led to improved healing and a good outcome.
- MeSH
- Infant MeSH
- Ring Chromosomes * MeSH
- Humans MeSH
- Chromosomes, Human, Pair 18 genetics MeSH
- Cleft Palate * genetics surgery MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Review MeSH
BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disorder with significant clinical implications, including life-threatening myasthenic crises and exacerbations. Understanding real-world treatment patterns, especially associated direct medical costs, is essential for the effective management of healthcare delivery. METHODS: We conducted a descriptive cohort study using health administrative claims data from the Czech Republic covering more than 1,500 prevalent MG patients. Data were analysed for healthcare resource utilization, medication costs, and hospitalization rates related to MG and its complications. RESULTS: Acetylcholine inhibitors and corticosteroids were widely prescribed, with 91.1% and 75.2% of patients receiving them at least once, respectively. Immunosuppressive therapy was given to 45.2% of patients. Myasthenic crises occurred in 2% of patients, with a mean hospitalization cost of 21,020 EUR, while exacerbations occurred in 9.2% of patients, with lower costs (5,951 EUR per hospitalization). Outpatient intravenous immunoglobulin and plasma exchange therapies incurred additional costs of 20,700 EUR and 18,206 EUR per person-year, respectively. The mean total cost per patient-year was 1,271 EUR, with significant cost differences among patients with different treatment patterns. CONCLUSION: This study offers real-world insights into the treatment patterns and associated direct medical costs of MG in the Czech Republic. Myasthenic crises and exacerbations pose considerable cost burdens, while outpatient therapies and common pharmacotherapies are less costly. These findings are vital for healthcare planning, economic evaluation, and resource allocation, potentially leading to enhanced patient care and outcomes.
- MeSH
- Adult MeSH
- Hospitalization economics MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Myasthenia Gravis * economics therapy drug therapy MeSH
- Health Care Costs MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.
- MeSH
- Acrylic Resins * chemistry MeSH
- Calorimetry, Differential Scanning MeSH
- X-Ray Diffraction MeSH
- Hydrogels * chemistry MeSH
- Hydrogen-Ion Concentration MeSH
- Rabbits MeSH
- Drug Delivery Systems MeSH
- Delayed-Action Preparations chemistry pharmacokinetics MeSH
- Microscopy, Electron, Scanning MeSH
- Drug Carriers chemistry MeSH
- Poloxamer * chemistry MeSH
- Spectroscopy, Fourier Transform Infrared MeSH
- Thermogravimetry MeSH
- Timolol * administration & dosage pharmacokinetics chemistry MeSH
- Drug Liberation MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The aging process is intricately linked to alterations in cellular and tissue structures, with the respiratory system being particularly susceptible to age-related changes. Therefore, this study aimed to profile the activity of proteases using activity-based probes in lung tissues of old and young rats, focusing on the expression levels of different, in particular cathepsins G and X and matrix Metalloproteinases (MMPs). Additionally, the impact on extracellular matrix (ECM) components, particularly fibronectin, in relation to age-related histological and ultrastructural changes in lung tissues was investigated. MATERIALS AND METHODS: Lung tissues from old and young rats were subjected to activity-based probe profiling to assess the activity of different proteases. Expression levels of cathepsins G and X were quantified, and zymography was performed to evaluate matrix metalloproteinases activity. Furthermore, ECM components, specifically fibronectin, were examined for signs of degradation in the old lung tissues compared to the young ones. Moreover, histological, immunohistochemical and ultrastructural assessments of old and young lung tissue were also conducted. RESULTS: Our results showed that the expression levels of cathepsins G and X were notably higher in old rat lung tissues in contrast to those in young rat lung tissues. Zymography analysis revealed elevated MMP activity in the old lung tissues compared to the young ones. Particularly, significant degradation of fibronectin, an essential ECM component, was observed in the old lung tissues. Numerous histological and ultrastructural alterations were observed in old lung tissues compared to young lung tissues. DISCUSSION AND CONCLUSION: The findings indicate an age-related upregulation of cathepsins G and X along with heightened MMP activity in old rat lung tissues, potentially contributing to the degradation of fibronectin within the ECM. These alterations highlight potential mechanisms underlying age-associated changes in lung tissue integrity and provide insights into protease-mediated ECM remodeling in the context of aging lungs.
- MeSH
- Extracellular Matrix metabolism ultrastructure MeSH
- Fibronectins * metabolism MeSH
- Cathepsin G metabolism MeSH
- Rats MeSH
- Lysosomes ultrastructure metabolism MeSH
- Matrix Metalloproteinases metabolism MeSH
- Lung * ultrastructure metabolism MeSH
- Peptide Hydrolases metabolism MeSH
- Aging * metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Impaired physical performance and muscle strength are recognized risk factors for fragility fractures, frequently associated with osteoporosis and sarcopenia. However, the integration of muscle strength and physical performance in the comprehensive assessment of fracture risk is still debated. Therefore, this cross-sectional study aimed to assess the potential role of hand grip strength (HGS) and short physical performance battery (SPPB) for predicting fragility fractures and their correlation with Fracture Risk Assessment Tool (FRAX) with a machine learning approach. METHODS: In this cross-sectional study, a group of postmenopausal women underwent assessment of their strength, with the outcome measured using the HSG, their physical performance evaluated using the SPPB, and the predictive algorithm for fragility fractures known as FRAX. The statistical analysis included correlation analysis using Pearson's r and a decision tree model to compare different variables and their relationship with the FRAX Index. This machine learning approach allowed to create a visual decision boundaries plot, providing a dynamic representation of variables interactions in predicting fracture risk. RESULTS: Thirty-four patients (mean age 63.8±10.7 years) were included. Both HGS and SPPB negatively correlate with FRAX major (r=-0.381, P=0.034; and r=-0.407, P=0.023 respectively), whereas only SPPB significantly correlated with an inverse proportionality to FRAX hip (r=-0.492, P=0.001). According to a machine learning approach, FRAX major ≥20 and/or hip ≥3 might be reported for an SPPB<6. Concurrently, HGS<17.5 kg correlated with FRAX major ≥20 and/or hip ≥3. CONCLUSIONS: In light of the major findings, this cross-sectional study using a machine learning model related SPPB and HGS to FRAX. Therefore, a precise assessment including muscle strength and physical performance might be considered in the multidisciplinary assessment of fracture risk in post-menopausal women.
- MeSH
- Risk Assessment MeSH
- Bone Density * physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Osteoporotic Fractures * epidemiology etiology MeSH
- Postmenopause MeSH
- Cross-Sectional Studies MeSH
- Risk Factors MeSH
- Aged MeSH
- Hand Strength MeSH
- Physical Functional Performance MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.
- MeSH
- Antidepressive Agents adverse effects MeSH
- Indans * MeSH
- Serotonin and Noradrenaline Reuptake Inhibitors * adverse effects MeSH
- Humans MeSH
- Oxadiazoles * MeSH
- Multiple Sclerosis * chemically induced MeSH
- Selective Serotonin Reuptake Inhibitors adverse effects MeSH
- Serotonin MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.
- MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive * drug therapy genetics MeSH
- Imatinib Mesylate therapeutic use MeSH
- Protein Kinase Inhibitors therapeutic use MeSH
- Humans MeSH
- Membrane Transport Proteins therapeutic use MeSH
- Prognosis MeSH
- Antineoplastic Agents * adverse effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The current study investigates attitudes toward one form of sex for resources: the so-called sugar relationships, which often involve exchanges of resources for sex and/or companionship. The present study examined associations among attitudes toward sugar relationships and relevant variables (e.g., sex, sociosexuality, gender inequality, parasitic exposure) in 69,924 participants across 87 countries. Two self-report measures of Acceptance of Sugar Relationships (ASR) developed for younger companion providers (ASR-YWMS) and older resource providers (ASR-OMWS) were translated into 37 languages. We tested cross-sex and cross-linguistic construct equivalence, cross-cultural invariance in sex differences, and the importance of the hypothetical predictors of ASR. Both measures showed adequate psychometric properties in all languages (except the Persian version of ASR-YWMS). Results partially supported our hypotheses and were consistent with previous theoretical considerations and empirical evidence on human mating. For example, at the individual level, sociosexual orientation, traditional gender roles, and pathogen prevalence were significant predictors of both ASR-YWMS and ASR-OMWS. At the country level, gender inequality and parasite stress positively predicted the ASR-YWMS. However, being a woman negatively predicted the ASR-OMWS, but positively predicted the ASR-YWMS. At country-level, ingroup favoritism and parasite stress positively predicted the ASR-OMWS. Furthermore, significant cross-subregional differences were found in the openness to sugar relationships (both ASR-YWMS and ASR-OMWS scores) across subregions. Finally, significant differences were found between ASR-YWMS and ASR-OMWS when compared in each subregion. The ASR-YWMS was significantly higher than the ASR-OMWS in all subregions, except for Northern Africa and Western Asia.
- MeSH
- Sugars * MeSH
- Interpersonal Relations MeSH
- Humans MeSH
- Sex Characteristics MeSH
- Attitude MeSH
- Sexual Behavior * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
This is the second in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on establishing and maintaining health. The guidance is produced using an evidence-based framework and with wide stakeholder engagement, including people from the CF community. Authors provided a narrative description of their topic and statements, which were more directive. These statements were reviewed by a Delphi exercise, achieving good levels of agreement from a wide group for all statements. This guidance reinforces the importance of a multi-disciplinary CF team, but also describes developing models of care including virtual consultations. The framework for health is reinforced, including the need for a physically active lifestyle and the strict avoidance of all recreational inhalations, including e-cigarettes. Progress with cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is reviewed, including emerging adverse events and advice for dose reduction and interruption. This paper contains guidance that is pertinent to all people with CF regardless of age and eligibility for and access to modulator therapy.
Daunorubicin (DNR) is an anthracycline antibiotic originating from soil-dwelling actinobacteria extensively used to treat malignant tumors. Over the decades, extensive attempts were made to enhance the production of anthracyclines by introducing genetic modifications and mutations in combination with media optimization, but the target production levels remain comparatively low. Developing an appropriate culture medium to maximize the yield of DNR and preventing autotoxicity for the producing organism remains a challenge. Our prospective review sheds light on a method involving perturbation that enhances the precursors to regulate the type II PKS pathway, enhancing cells' capacity to increase secondary metabolite production. The suggested method also entails the preparation of culture media for the cultivation of Streptomyces sp. and enhanced yield of DNR, as well as making it inactive with iron or its reduced forms following efflux from the producer. The iron or iron-DNR complex is encapsulated by oleic acid or lipid micelle layers in the culture media, finally resulting in the generated inactive DNR and the DNR-iron-oil complex. This idea has the potential to protect the producer organism from autotoxicity and prevent the inhibition of metabolite production. The approach of substituting sugar with oil in culture media has a dual role wherein it promotes Streptomyces growth by utilizing lipids as an energy source and encapsulating the generated DNR-iron complex in the medium. In this review, we discussed aspects like anthracycline producers, biosynthesis pathways, and gene regulation; side effects of DNR; mechanisms for autotoxicity evasion; and culture media components for the enhancement of DNR production in Streptomyces sp. We anticipate that our work will help researchers working with secondary metabolites production and decipher a methodology that would enhance DNR yield and facilitate the extraction of the resulting DNR by lowering costs in large-scale fermentation.
- Publication type
- Journal Article MeSH
- Review MeSH
