Leber hereditary optic neuropathy in Czechia and Slovakia: Quality of life and costs from patient perspective.

Introduction: Leber hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease causing dyschromatopsia and progressive central visual loss that is subacute in progression and painless. Several studies have been published assessing QoL in patients with LHON, but no estimate of the economic burden has been reported to date. This study aims to quantify direct non-medical and indirect costs (productivity loss) incurred by LHON patients and their informal caregivers in Czechia and Slovakia, as well as to assess their quality of life.

Evaluation of adherence to abiraterone therapy in prostate cancer patients based on a population pharmacokinetic model.

Aims: Abiraterone treatment requires regular drug intake under fasting conditions due to pronounced food effect, which may impact patient adherence. The aim of this prospective study was to evaluate adherence to abiraterone treatment in patients with prostate cancer. To achieve this aim, an abiraterone population pharmacokinetic model was developed and patients' adherence has been estimated by comparison of measured levels of abiraterone with population model-based simulations.

Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer.

Objective: To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs.

Methods: Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels).

Blau Syndrome: Challenging Molecular Genetic Diagnostics of Autoinflammatory Disease.

The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The mutational hot spot located in exon 4 was Sanger sequenced in all three probands.

Germline pathogenic variants in the MRE11, RAD50, and NBN (MRN) genes in cancer predisposition: A systematic review and meta-analysis.

The MRE11, RAD50, and NBN genes encode the MRN complex sensing DNA breaks and directing their repair. While carriers of biallelic germline pathogenic variants (gPV) develop rare chromosomal instability syndromes, the cancer risk in heterozygotes remains controversial. We performed a systematic review and meta-analysis of 53 studies in patients with different cancer diagnoses to better understand the cancer risk.

Analysis of striatal connectivity corresponding to striosomes and matrix in de novo Parkinson's disease and isolated REM behavior disorder.

Striosomes and matrix are two compartments that comprise the striatum, each having its own distinct immunohistochemical properties, function, and connectivity. It is currently not clear whether prodromal or early manifest Parkinson's disease (PD) is associated with any striatal matrix or striosomal abnormality. Recently, a method of striatal parcellation using probabilistic tractography has been described and validated, using the distinct connectivity of these two compartments to identify voxels with striosome- and matrix-like connectivity.

Alzheimer's disease approaches - Focusing on pathology, biomarkers and clinical trial candidates.

The strategy for the development of new drugs for Alzheimer's disease (AD) recognizes that an effective therapy requires early therapeutic intervention and a multifactorial approach that considers the individual initiators of AD development. Current knowledge of AD includes the understanding of pathophysiology, risk factors, biomarkers, and the evolving patterns of biomarker abnormalities. This knowledge is essential in identifying potential molecular targets for new drug development.

Efficacy of rehabilitation treatments in improving functioning in patients with fibromyalgia: A systematic review and meta-analysis of randomized controlled trials.

Background: Fibromyalgia is a debilitating condition marked by persistent pain and reduced functionality. Various therapeutic methods have been suggested to alleviate symptoms in individuals with fibromyalgia, yet the impact of diverse rehabilitation strategies remains unclear.

Objective: This systematic review and meta-analysis aimed at assessing the efficacy of rehabilitation interventions in improving functioning in fibromyalgia patients.

An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers.

The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the "traditional" immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing.

Leg stereotypy syndrome: phenomenological and quantitative analysis.

Background: Leg stereotypy syndrome (LSS) is a very common, yet underrecognized condition. The pathophysiology of the condition is not well understood.

Objective: To evaluate and describe the visual kinematic characteristics of the repetitive leg movements in individuals with LSS.

Vancomycin population pharmacokinetics and dosing proposal for the initial treatment in obese adult patients.

Aim: The aim of this study was to develop a vancomycin population pharmacokinetic model in adult obese patients and propose covariate-based dosing individualization in order to maximize the achievement of the newly recommended PK/PD target, according to a revised consensus guideline from 2020.

Methods: Therapeutic drug monitoring data from initial vancomycin therapy (first 3 days of treatment) in adult obese (BMI ≥ 30 kg/m) patients from 2013 to 2022 were analyzed using a non-linear mixed-effects modeling method, and Monte Carlo simulations were then used to find the optimal dosage maximizing the PK/PD target attainment.

Results: A total of 147 vancomycin serum levels obtained from 138 patients were included in the analysis.

Vancomycin loading dose individualization in a population of obese patients undergoing haemodialysis based on population pharmacokinetic model.

This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment.

RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin.

RAD18 is an E3 ubiquitin ligase that prevents replication fork collapse by promoting DNA translesion synthesis and template switching. Besides this classical role, RAD18 has been implicated in homologous recombination; however, this function is incompletely understood. Here, we show that RAD18 is recruited to DNA lesions by monoubiquitination of histone H2A at K15 and counteracts accumulation of 53BP1.

Komrower Memorial Lecture 2023. Molecular basis of phenotype expression in homocystinuria: Where are we 30 years later?

This review summarises progress in the research of homocystinuria (HCU) in the past three decades. HCU due to cystathionine β-synthase (CBS) was discovered in 1962, and Prof. Jan Peter Kraus summarised developments in the field in the first-ever Komrower lecture in 1993.

p.L1795F LRRK2 variant is a common cause of Parkinson's disease in Central Europe.

Pathogenic variants in are one of the most common genetic risk factors for Parkinson's disease (PD). Recently, the lesser-known p.L1795F variant was proposed as a strong genetic risk factor for PD, however, further families are currently lacking in literature.

Parallel DNA/RNA NGS Using an Identical Target Enrichment Panel in the Analysis of Hereditary Cancer Predisposition.

Germline DNA testing using the next-gene-ration sequencing (NGS) technology has become the analytical standard for the diagnostics of hereditary diseases, including cancer. Its increasing use places high demands on correct sample identification, independent confirmation of prioritized variants, and their functional and clinical interpretation. To streamline these processes, we introduced parallel DNA and RNA capture-based NGS using identical capture panel CZECANCA, which is routinely used for DNA analysis of hereditary cancer predisposition.

Oral health in youth with visual impairment: A longitudinal survey.

This longitudinal survey aims to demonstrate improvement in oral hygiene among a group of youth with visual impairment (VI) achieved by repeated oral hygiene training, compare their progress with healthy peers (CG) and assess their oral health knowledge. In 100 VI (55♀, 45♂; ± 17.8 years) and 45 CG (23♀, 22♂; ± 17.

Electrospun poly(l-lactide--dl-lactide) nanofibrous scaffold as substrate for limbal epithelial cell cultivation.

Ultrathin electrospun poly (l-lactide--dl-lactide) nanofibrous membranes coated with fibronectin were explored as scaffolds for the cultivation of limbal epithelial cells (LECs) for the treatment of limbal stem cell deficiency. The developed scaffolds were compared with the "gold-standard" fibrin gel. The resulting membranes composed of nanofibers possessed a very low thickness of 4 μm and allowed very good optical transparency in the wet state.

Lessons Learned from Telemedicine in Adolescent Obesity: Results of a Pilot Study.

The rising prevalence of obesity in children calls for new strategies for the provision of effective care by a multidisciplinary team. Telemedicine has overall proven to be an effective tool for promoting a healthy lifestyle. The main objective of the current paper is to present the protocol of our ongoing CardioMetabolic Prevention (CAMP) study and compare its design with published studies on telemedicine in paediatric obesity.

Highly variable biological effects of statins on cancer, non-cancer, and stem cells in vitro.

Statins, the drugs used for the treatment of hypercholesterolemia, have come into the spotlight not only as chemoadjuvants, but also as potential stem cell modulators in the context of regenerative therapy. In our study, we compared the in vitro effects of all clinically used statins on the viability of human pancreatic cancer (MiaPaCa-2) cells, non-cancerous human embryonic kidney (HEK 293) cells and adipose-derived mesenchymal stem cells (ADMSC). Additionally, the effect of statins on viability of MiaPaCa-2 and ADMSC cells spheroids was tested.

Evidence for Therapeutic Drug Monitoring of Atypical Antipsychotics.

Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder, and related psychiatric conditions. The plasma concentration of antipsychotic drugs is a valid measure of the drug at its primary target structure in the brain, and therefore determines the efficacy and safety of these drugs. However, despite the well-known high variability in pharmacokinetics of these substances, psychiatric medication is usually administered in uniform dosage schedules.

Echocardiography predictors of sustained sinus rhythm after cardioversion of supraventricular arrhythmia in patients with septic shock.

Purpose: The echocardiography parameters may predict the maintenance of sinus rhythm after cardioversion of a supraventricular arrhythmia (SVA).

Materials And Methods: Patients in septic shock with onset of an SVA, normal to moderately reduced LV systolic function (EF_LV˃̳35%) and on a continuous noradrenaline of <1.0 μg/kg.