Rejected

The research considers the impact of genotype-inferred variability on blood levels of amitriptyline and its main metabolites, as may be moderated by phenocopying. and genotypes, and serum concentrations of amitriptyline, nortriptyline and hydroxymetabolites, were determined in 33 outpatients. Co-medications were reviewed to identify CYP inhibition risk. CYP2C19 metabolizer status explained interpatient variation in nortriptyline to amitriptyline concentration ratios. The hydroxymetabolite to parent ratios increased with higher CYP2D6 activity scores and lower CYP2D6 inhibition risk. In patients at high CYP2D6 inhibition risk, the amitriptyline + nortriptyline concentration was, on average, 52% above the higher end of expected ranges. Practical construal of pharmacogenetics and drug interactions tantamount to aberrant metabolism can facilitate patient-tailored use of the established drug.

Multiple sclerosis (MS) patients receiving natalizumab and who are at risk of developing progressive multifocal leukoencephalopathy (PML) often switch to other high-efficacy disease-modifying therapies including fingolimod as a risk mitigation strategy, which could impact treatment safety and effectiveness. The TRANSITION study aimed to evaluate the safety of fingolimod over two years in patients with MS after switching from natalizumab in a real-world setting. The safety and effectiveness were assessed by monitoring serious and other adverse events (SAEs, AEs). We assessed effectiveness by recording relapses, Expanded Disability Status Scale (EDSS) scores, and MRI activity. Of 637 patients enrolled, 505 completed the study (mean age, 42 years). Overall, 72.8% and 12.7% experienced AEs and SAEs respectively. The most common AEs were fatigue, headache, and urinary tract infection; no cases of PML were observed. Fingolimod treatment resulted in low disease activity. Patients with ≤8 weeks washout period had a markedly lower risk of relapses (4.5%) than those with >8 weeks (51.4%). In patients switching from natalizumab to fingolimod, no new safety signals with overall low relapse activity were observed in patients with washout latencies of ≤8 weeks before fingolimod initiation. Fingolimod was found to be safe and effective in patients transitioning from natalizumab.

People with fibromyalgia could experience physical and cognitive impairments. Furthermore, when performing two tasks at the same time, people with fibromyalgia showed a higher dual-task cost compared to a single task than healthy people. This may result in poorer performance of activities of daily living that are commonly presented as a combination of two or more tasks. Transcranial direct current stimulation (tDCS) is a promising nonpharmacological therapy. However, there is controversy regarding the intensities and the effectiveness of this therapy. Thus, the present study will aim: (1) to compare the effectiveness and the impact of two tDCS intensities (1 mA and 2 mA) on cognitive, motor, brain functions, and cardiac autonomic modulation; (2) to study the impact of tDCS on the dual-task performance and creativity after applying tDCS in dorsolateral prefrontal cortex. In this study, 26 women will participate and will be divided into two groups: women with fibromyalgia ( = 13), and healthy controls ( = 13). A reduction in cognitive-motor interference in dual-task performance is expected, as well as a modification in neurophysiological parameters and an improvement in cardiac autonomic modulation. Lastly, no different effects are expected depending on the stimulation intensity applied. The obtained results will help to determine if tDCS in the dorsolateral prefrontal cortex could improve the occupational performance of women with fibromyalgia.

The aim of this study was to evaluate the prevalence and severity of overactive bladder syndrome (OAB) and sexual dysfunction in fibromyalgia (FM) patients, as well as their relationship with disease severity.

Silent corticotroph adenomas (SCAs) behave more aggressively than other non-functioning adenomas (NFAs). This study aims to expand the body of knowledge of the behavior of SCAs.

Progressive Familial Intrahepatic Cholestasis, is an expanding group of autosomal recessive intrahepatic cholestatic disorders. Recently, Next Generation Sequencing allowed identifying new genes responsible for new specific disorders. Two biochemical phenotypes have been identified according to gamma-glutamyltransferase (GGT) activity. Mutations of the myosin 5B gene (MYO5B) are known to cause Microvillus Inclusion Disease. Recently, different mutations in MYO5B gene have been reported in patients with low-GGT cholestasis.

Children may be greatly affected by events that increase stress in individuals in general and are reported as the vulnerable groups during the coronavirus disease-19 (COVID-19) pandemic. But most of the studies in the literature investigating the mental effects of the pandemic on children were conducted with healthy children and limited study has evaluated the effect on children diagnosed with COVID-19. The aim of this study is to determine the anxiety level in paediatric patients diagnosed with COVID-19 and the affecting factors.

Analyses of lymphoid organs are required to further elucidate the pathogenesis of inflammatory diseases like rheumatoid arthritis (RA). Yet, invasive tissue collection methods are scarcely applied, because they are often considered burdensome, although patients do not always consider invasive methods as a high burden. We aimed to investigate the perspectives of study participants undergoing ultrasound-guided inguinal lymph node (LN) needle biopsy sampling and determine the molecular and cellular quantity and quality of LN biopsies.

Recommendations for managing patients with cerebral cryptococcomas are scarce across multiple clinical guidelines. Due to the deficiency of high-quality data coupled with an increasing number of at-risk patients, the purpose of this review is to describe the demographic characteristics, causative pathogen, intracranial imaging, surgical and/or pharmacological interventions, as well as outcomes of patients with cerebral cryptococcomas to improve recognition and management.