- MeSH
- fytoterapie metody MeSH
- léčivé čaje MeSH
- lidé MeSH
- péče o sebe MeSH
- premenstruační syndrom * diagnóza terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- populární práce MeSH
- MeSH
- dítě MeSH
- lidé MeSH
- rodičovství MeSH
- sexuální výchova MeSH
- výchova dítěte MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.
- MeSH
- amyotrofická laterální skleróza * farmakoterapie MeSH
- inzulin škodlivé účinky MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Postoperative constipation (PC) in patients with imperforate anus and perineal fistula (PF) has been reported in up to 60%. Histological studies of PF revealed innervation anomalies which seem to be one of the reasons for PC. Perioperative histologically controlled fistula resection (PHCFR) allows appropriate resection of PF and pull-down normoganglionic rectum at the time of posterior sagittal anorectoplasty (PSARP). MATERIALS AND METHODS: A total of 665 patients with anorectal malformations underwent surgery between 1991 and 2021. Of these, 364 presented PF; 92 out of them (41 F) were studied. Patients with sacral and spinal cord anomalies, neurological disorders, and cut-back anoplasty were excluded. PSARP was done on all patients. Hematoxylin-eosin staining and NADH Tetrazolium-reductase histochemical method were used. Four and more ganglion cells in the myenteric plexus represented a sufficient length of the resection. The continence was scored according to the modified Krickenbeck scoring system. Final scores ranged from 1 to 7 points. Values are given as median. RESULTS: A total of 65 (70.7%) patients presented an aganglionic segment in PF, and 27 patients presented hypoganglionosis. The median length of the resected fistula was 25 mm (interquartile range [IQR]: 20-30). The median total continence score was 7 (IQR: 6-7). Post-op constipation was observed in 6/92 (6.5%) patients. CONCLUSION: PHCFR diminished PC to 6.5% of patients.
- MeSH
- anální atrézie * chirurgie MeSH
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- perineum chirurgie MeSH
- pooperační komplikace etiologie MeSH
- předškolní dítě MeSH
- rektální píštěl * chirurgie MeSH
- rektum chirurgie abnormality MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- zácpa etiologie chirurgie MeSH
- zákroky plastické chirurgie metody MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
DNA double-strand breaks (DSBs) represent a lethal form of DNA damage that can trigger cell death or initiate oncogenesis. The activity of RNA polymerase II (RNAPII) at the break site is required for efficient DSB repair. However, the regulatory mechanisms governing the transcription cycle at DSBs are not well understood. Here, we show that Integrator complex subunit 6 (INTS6) associates with the heterotrimeric sensor of ssDNA (SOSS1) complex (comprising INTS3, INIP and hSSB1) to form the tetrameric SOSS1 complex. INTS6 binds to DNA:RNA hybrids and promotes Protein Phosphatase 2A (PP2A) recruitment to DSBs, facilitating the dephosphorylation of RNAPII. Furthermore, INTS6 prevents the accumulation of damage-associated RNA transcripts (DARTs) and the stabilization of DNA:RNA hybrids at DSB sites. INTS6 interacts with and promotes the recruitment of senataxin (SETX) to DSBs, facilitating the resolution of DNA:RNA hybrids/R-loops. Our results underscore the significance of the tetrameric SOSS1 complex in the autoregulation of DNA:RNA hybrids and efficient DNA repair.
- MeSH
- DNA vazebné proteiny metabolismus MeSH
- DNA-helikasy metabolismus genetika MeSH
- DNA * metabolismus chemie MeSH
- dvouřetězcové zlomy DNA * MeSH
- fosforylace MeSH
- homeostáza genetika MeSH
- lidé MeSH
- oprava DNA * MeSH
- proteinfosfatasa 2 metabolismus genetika MeSH
- R-smyčka MeSH
- RNA-helikasy metabolismus genetika MeSH
- RNA-polymerasa II * metabolismus MeSH
- RNA * metabolismus genetika chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Activation of nuclear factor-kappa B (NF-κB) signalling is key in the pathogenesis of chronic kidney disease (CKD). However, a certain level of NF-κB activity is necessary to enable tissue repair. METHODS: The relationship between activated and inactivated NF-κB signaling and the pathogenesis of CKD was investigated using mouse models of NF-κB partial inactivation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into alanine) and activation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into serine). RESULTS: The density of CD3, CD8, CD68 positive cells, as well as the expression of interleukin 6, Tumor necrosis factor receptor associated factor 1 and Nef-associated factor 1 in the kidney tissues of NF-κBC59A mice were reduced, whereas an opposing pattern was observed in the NF-κBC59S mice. Blood pressure, kidney fibrosis (analyzed by periodic acid-Schiff, Masson trichrome and Sirius Red staining, as well as α-SMA immunofluorescence), serum creatinine and urinary albumin-to-creatinine ratio are markedly increased in NF-κB-activated and -inactivated mice compared with controls. Transmission electron microscopy indicated that the glomerular basement membrane was thicker in both NF-κBC59A and NF-κBC59S mice compared with wild-type mice. CONCLUSIONS: Using mice models with partially activated and inactivated NF-κB pathways suggests that there is an apparently U-shaped relationship between blood pressure, kidney function as well as morphology and the activation of the NF-κB pathway. A certain optimal activity of the NF-κB pathway seems to be important to maintain optimal kidney function and morphology.
- MeSH
- chronická renální insuficience metabolismus patologie etiologie MeSH
- fibróza MeSH
- hypertenze * metabolismus etiologie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- NF-kappa B * metabolismus MeSH
- signální transdukce * MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND IMPORTANCE: In 2018, the European Society of Cardiology (ESC) produced syncope guidelines that for the first-time incorporated Emergency Department (ED) management. However, very little is known about the characteristics and management of this patient group across Europe. OBJECTIVES: To examine the prevalence, clinical presentation, assessment, investigation (ECG and laboratory testing), management and ESC and Canadian Syncope Risk Score (CSRS) categories of adult European ED patients presenting with transient loss of consciousness (TLOC, undifferentiated or suspected syncope). DESIGN: Prospective, multicentre, observational cohort study. SETTINGS AND PARTICIPANTS: Adults (≥18 years) presenting to European EDs with TLOC, either undifferentiated or thought to be of syncopal origin. MAIN RESULTS: Between 00:01 Monday, September 12th to 23:59 Sunday 25 September 2022, 952 patients presenting to 41 EDs in 14 European countries were enrolled from 98 301 ED presentations (n = 40 sites). Mean age (SD) was 60.7 (21.7) years and 487 participants were male (51.2%). In total, 379 (39.8%) were admitted to hospital and 573 (60.2%) were discharged. 271 (28.5%) were admitted to an observation unit first with 143 (52.8%) of these being admitted from this. 717 (75.3%) participants were high-risk according to ESC guidelines (and not suitable for discharge from ED) and 235 (24.7%) were low risk. Admission rate increased with increasing ESC high-risk factors; 1 ESC high-risk factor; n = 259 (27.2%, admission rate=34.7%), 2; 189 (19.9%; 38.6%), 3; 106 (11.1%, 54.7%, 4; 62 (6.5%, 60.4%), 5; 48 (5.0%, 67.9%, 6+; 53 (5.6%, 67.9%). Furthermore, 660 (69.3%), 250 (26.3%), 34 (3.5%) and 8 (0.8%) participants had a low, medium, high, and very high CSRS respectively with respective admission rates of 31.4%, 56.0%, 76.5% and 75.0%. Admission rates (19.3-88.9%), use of an observation/decision unit (0-100%), and percentage high-risk (64.8-88.9%) varies widely between countries. CONCLUSION: This European prospective cohort study reported a 1% prevalence of syncope in the ED. 4 in 10 patients are admitted to hospital although there is wide variation between country in syncope management. Three-quarters of patients have ESC high-risk characteristics with admission percentage rising with increasing ESC high-risk factors.
- MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- synkopa * diagnóza epidemiologie terapie MeSH
- urgentní služby nemocnice * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Kanada MeSH