This review describes our experience with native tissue repair of the visceral pelvic fascia, the perineum, and anal sphincters in women. We propose that complex repair of the pelvic floor should consider vaginal support in all three anatomical Delancey's levels, together with more caudal structures-the external and internal anal sphincters. Original illustrations were created to facilitate the understanding of the complex anatomy of common multi-level defects. As the integrity of connective tissue adds to various aspects of the delicate function of the female pelvic floor, it is complete and as perfect as possible repair is a common goal of both gynecologists and colorectal specialists.

• MeSH
• Anal Canal * surgery   MeSH
• Fascia MeSH
• Gynecologic Surgical Procedures * methods   MeSH
• Humans MeSH
• Pelvic Floor Disorders * surgery   MeSH
• Pelvic Floor * surgery   MeSH
• Perineum surgery   MeSH
• Pelvic Organ Prolapse * surgery   MeSH
• Vagina surgery   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil's activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. METHODS: Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil's modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. RESULTS: Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. CONCLUSIONS: Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.

• MeSH
• Adult MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Young Adult MeSH
• Modafinil * pharmacology   administration & dosage   MeSH
• Cerebellum * drug effects   diagnostic imaging   metabolism   MeSH
• Neocortex drug effects   metabolism   diagnostic imaging   MeSH
• Neural Pathways drug effects   metabolism   MeSH
• Wakefulness-Promoting Agents pharmacology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

OBJECTIVES: The efficacy and safety of macitentan, an endothelin receptor antagonist, were assessed in a 52-week, prospective, multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessing the efficacy and safety of macitentan in Fontan-palliated adult and adolescent patients (RUBATO-DB) and an open-label extension trial (RUBATO-OL). METHODS: Patients aged 12 years and older with New York Heart Association functional class II or III underwent total cavopulmonary connection more than 1 year before screening and showed no signs of Fontan failure/clinical deterioration. In RUBATO-DB, the primary efficacy end point was change in peak oxygen consumption from baseline to week 16; secondary end points were change from baseline over 52 weeks in peak oxygen consumption and change in mean count/minute of daily physical activity via accelerometer from baseline to week 16. Safety was assessed throughout both studies. RESULTS: In RUBATO-DB, 137 patients were randomized to macitentan 10 mg (n = 68) or placebo (n = 69); 92.7% completed 52-week double-blind treatment. At week 16, mean ± SD change in peak oxygen consumption was -0.16 ± 2.86 versus -0.67 ± 2.66 mL/kg/minute with macitentan versus placebo (median unbiased treatment difference estimate, 0.62 mL/kg/minute [99% repeated CI, -0.62 to 1.85]; P = .19). No treatment effect was observed in either of the secondary end points. During RUBATO-DB, most common adverse events with macitentan were headache, nasopharyngitis, and pyrexia. Across RUBATO-DB and RUBATO-OL, most common adverse events were COVID-19, headache, and fatigue. RUBATO-OL was prematurely discontinued because RUBATO-DB did not meet its primary or secondary end point. CONCLUSIONS: The primary end point of RUBATO-DB was not met; macitentan did not improve exercise capacity versus placebo in patients with Fontan palliation. Macitentan was generally well tolerated over long-term treatment.

• MeSH
• Endothelin Receptor Antagonists therapeutic use   adverse effects   MeSH
• Time Factors MeSH
• Child MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Fontan Procedure * adverse effects   MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Palliative Care MeSH
• Prospective Studies MeSH
• Pyrimidines * therapeutic use   adverse effects   MeSH
• Oxygen Consumption drug effects   MeSH
• Sulfonamides * therapeutic use   adverse effects   MeSH
• Exercise Tolerance drug effects   MeSH
• Heart Defects, Congenital surgery   physiopathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

Tyreopatie a diabetes mellitus 2. typu patria medzi celosvetovo najčastejšie ochorenia v ambulantnej praxi. Vzťah medzi diabetes mellitus 1. typu a ochoreniami štítnej žľazy je známy a popísaný, ale vzťah tyreopatií k diabetu 2. typu nie je doteraz dostatočne objasnený, aj keď súvis medzi nimi odhaľuje stále viac štúdií. Diabetes môže ovplyvňovať funkciu štítnej žľazy aj nepriamo prostredníctvom niektorých perorálnych antidiabetík.

Thyroid diseases and type 2 diabetes mellitus are the two most common endocrinological diseases worldwide. The relationship between type 1 diabetes mellitus and thyroid diseases is known and described, but the relationship between thyreopathies and type 2 diabetes is not clarified sufficiently through that studies manifest increasingly the connection between them. Diabetes also can affect thyroid gland function indirectly by some peroral antidiabetics.

BACKGROUND AND PURPOSE: Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting-state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph-theory-based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross-sectional fMRI analysis. METHODS: Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion-weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability. RESULTS: Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median -0.30/-0.06, interquartile range 0.55/0.54; p = 0.009, Mann-Whitney U test), yielding acceptable yet non-superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/-0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = -0.34, p = 0.010, n = 56) but neither gait nor disability. CONCLUSIONS: kD is a potential biomarker of CI and fatigue warranting further validation.

• MeSH
• Adult MeSH
• Cognitive Dysfunction etiology   physiopathology   diagnostic imaging   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Cross-Sectional Studies MeSH
• Multiple Sclerosis * complications   diagnostic imaging   physiopathology   MeSH
• Processing Speed MeSH
• Fatigue * physiopathology   etiology   diagnostic imaging   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

This study explored how the human cortical folding pattern composed of convex gyri and concave sulci affected single-subject morphological brain networks, which are becoming an important method for studying the human brain connectome. We found that gyri-gyri networks exhibited higher morphological similarity, lower small-world parameters, and lower long-term test-retest reliability than sulci-sulci networks for cortical thickness- and gyrification index-based networks, while opposite patterns were observed for fractal dimension-based networks. Further behavioral association analysis revealed that gyri-gyri networks and connections between gyral and sulcal regions significantly explained inter-individual variance in Cognition and Motor domains for fractal dimension- and sulcal depth-based networks. Finally, the clinical application showed that only sulci-sulci networks exhibited morphological similarity reductions in major depressive disorder for cortical thickness-, fractal dimension-, and gyrification index-based networks. Taken together, these findings provide novel insights into the constraint of the cortical folding pattern to the network organization of the human brain.

• MeSH
• Depressive Disorder, Major pathology   diagnostic imaging   MeSH
• Adult MeSH
• Connectome * MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Young Adult MeSH
• Cerebral Cortex * diagnostic imaging   anatomy & histology   MeSH
• Nerve Net * diagnostic imaging   anatomy & histology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Úvod: Počty císařských řezů (CS – cesarean section) celosvětově rostou, přičemž související poporodní komplikace jsou výrazně vyšší ve srovnání s vaginálním porodem. Řešení těchto komplikací pomocí optimalizovaného managementu a cílené fyzioterapie je klíčové pro zlepšení mateřských výsledků a kvality života. Cíl: Cílem této studie bylo zhodnotit účinnost fyzioterapie na úlevu od bolesti a obnovení funkční aktivity žen po CS. Materiál a metody: Do studie bylo zapojeno 91 pacientek, které byly přijaty do porodnické nemocnice pro elektivní CS. Kontrolní skupině (47 žen) byl poskytnut standardní předoperační a pooperační dohled. Intervenční skupina (44 pacientů) kromě standardní péče absolvovala fyzioterapii, která zahrnovala předoperační péči (fyzioterapeutický výcvik, edukační výcvik) a pooperační cvičení (dechové, oběhové a pánevní cvičení spolu s masáží pojiva). Výsledky po CS byly analyzovány po dobu 3 dnů. Výsledky: Nižší intenzita pooperačních bolestí a snazší chůze od 1. dne, nižší obtížnost při provádění funkčních činností 2. den (snazší otočení na lůžku a přechod do sedu), rychlejší obnova střevní motility v důsledku průchodu flatusu za 3,5 hod a defekace na 10 hod, snížená potřeba analgetik navíc 4,21krát (OR = 0,24; 95% CI 0,10–0,58; p = 0,02) a bylo zjištěno významné snížení doby trvání hospitalizace (OR = 0,24; 95% CI 0,09–0,57; p = 0,02). Závěr: Studie prokázala účinnost navrženého fyzioterapeutického programu v časném období po CS ve smyslu snížení bolesti a zlepšení obnovy funkční aktivity organizmu.

Background: Cesarean section (CS) rates are rising globally, with associated postpartum complications significantly higher compared to vaginal delivery. Addressing these complications through optimized management and targeted physiotherapy is crucial for improving maternal outcomes and quality of life. Objective: This study aimed to evaluate the effectiveness of physiotherapy on pain relief and restoration of functional activity in women after CS. Material and methods: 91 patients, who were admitted to an obstetric hospital for elective CS, were involved in the study. The control group (47 women) received standard pre- and postoperative supervision. The intervention group (44 patients), in addition to standard care, underwent physiotherapy, which included preoperative care (physiotherapy training, educational training), and postoperative exercises (breathing, circulation, and pelvic exercises, along with connective tissue massage). The results were analyzed after CS for 3 days. Results: A lower intensity of postoperative pain and easier walking from the 1st day, a lower level of difficulty in performing functional activities on the 2nd day (easier turning in bed and transition to a sitting position), faster recovery of intestinal motility due to the passage of flatus in 3.5 hours and the act of defecation after 10.0 hours, decreased requirement of extra analgesics by 4.21-fold (OR = 0.24; 95% CI 0.10–0.58; P = 0.02), and a significant reduction in the length of hospital stay (OR = 0.24; 95% CI 0.09–0.57; P = 0.02) were established. Conclusion: The study revealed the effectiveness of the proposed physiotherapy program in the early post-cesarean period in terms of reducing pain and improving restoration of the body’s functional activity.

Accelerated epigenetic aging has been associated with changes in cognition. However, due to the lack of neuroimaging epigenetics studies, it is still unclear whether accelerated epigenetic. Aging in young adulthood might underlie the relationship between altered brain dynamics and cognitive functioning. We conducted neuroimaging epigenetics follow-up of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort in young adulthood and tested the possible mediatory role of accelerated epigenetic aging in the relationship between dynamic functional connectivity (DFC) and worse cognition. A total of 240 young adults (51% men; 28-30 years, all of European ancestry) participated in the neuroimaging epigenetics follow-up. Buccal swabs were collected to assess DNA methylation and calculate epigenetic aging using Horvath's epigenetic clock. Full-scale IQ was assessed using the Wechsler adult intelligence scale (WAIS). Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired using a 3T Siemens Prisma MRI scanner, and DFC was assessed using mixture factor analysis, revealing information about the coverage of different DFC states. In women (but not men), lower coverage of DFC state 4 and thus lower frequency of epochs with high connectivity within the default mode network and between default mode, fronto-parietal, and visual networks was associated with lower full-scale IQ (AdjR2 = 0.05, std. beta = 0.245, p = 0.008). This relationship was mediated by accelerated epigenetic aging (ab = 7.660, SE = 4.829, 95% CI [0.473, 19.264]). In women, accelerated epigenetic aging in young adulthood mediates the relationship between altered brain dynamics and cognitive functioning. Prevention of cognitive decline should target women already in young adulthood.

• MeSH
• Default Mode Network * diagnostic imaging   physiology   MeSH
• Adult MeSH
• Epigenesis, Genetic * physiology   MeSH
• Intelligence * physiology   MeSH
• Cognition * physiology   MeSH
• Connectome * MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Magnetic Resonance Imaging MeSH
• DNA Methylation MeSH
• Young Adult MeSH
• Brain * diagnostic imaging   physiology   MeSH
• Nerve Net * diagnostic imaging   physiology   MeSH
• Aging * physiology   genetics   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

V revmatologické ambulanci se setkáváme s širokou paletou diagnóz. Pacienti přichází s příznaky zapadající spíše do degenerativních a funkčních poruch jako např. osteoartróza či osteoporóza. Setkáváme se ale i s pacienty se závažnými, někdy i život ohrožujícími nemocemi jako jsou systémové choroby pojiva, vaskulitidy či zánětlivé revmatické choroby. Předložené kazuistiky jsou z obou konců spektra pacientů v revmatologické ambulanci. První kazuistika je případ muže se subakutními bolestmi pohybového aparátu, hlavně ramenního kloubu, a únavovým syndromem. Druhý příběh popisuje pacientku s dlouhodobou diagnózou systémové sklerodermie. Obě kazuistiky popisují vliv psychosomatické intervence v akutní i dlouhodobé perspektivě a obě ilustrují, jak lze porozumět psychosociálnímu kontextu pacienta a jeho vlivu na somatické projevy

We detect a wide variety of diagnoses, in the rheumatology ambulancy,. Patients come with symptoms that fit more into degenerative and functional disorders such as osteoarthritis or osteoporosis. We also treat patients with serious systemic, sometimes life-threatening diseases such as connective tissue diseases, vasculitis or inflammatory rheumatic diseases. The presented case reports are from both ends of the spectrum of patients in the rheumatology clinic. The first case study is the case of a man with subacute musculoskeletal pain, shoulder joint especially and fatigue. The second case report describes a patient with a long-term diagnosis of systemic scleroderma. Both cases describe acute and long-term psychosomatic interventions. Detection of patient's psychosocial context may have an impact on somatic manifestations.

In this manuscript, we highlight the evolutionary origins of mitochondria from bacterial endosymbionts and explore their contributions to health, energy metabolism, and neural-immune communication. Mitochondrial adaptability and the roles played by these organelles in promoting oxygen-dependent ATP production provide critical regulation of cognition, motivation, and inflammation. Hypoxia has been identified as an important initiator of inflammation, neurodegeneration, and mitochondrial dysfunction, emphasizing the overall importance of oxygen homeostasis to health and well-being. The Behavior, Exercise, Relaxation, and Nutrition framework highlights these observations as tools that can be used to optimize mitochondrial efficiency. Interestingly, mitochondrial dysfunction may also be linked to psychiatric disorders (e.g., schizophrenia), a hypothesis that focuses on energy dynamics, a proposal that may extend our understanding of these disorders beyond traditional neurotransmitter-focused concepts. Collectively, these perspectives underscore the critical contributions of mitochondria to health and disease and offer a novel framework that may help to explain the connections featured in mind-body medicine.

• MeSH
• Biological Evolution MeSH
• Pain * metabolism   physiopathology   MeSH
• Exercise * physiology   MeSH
• Energy Metabolism * MeSH
• Cognition * physiology   MeSH
• Humans MeSH
• Mitochondria metabolism   MeSH
• Motivation * MeSH
• Pleasure * physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH