BACKGROUND: Children in agricultural areas are exposed to organophosphate (OP) and pyrethroid (PYR) insecticides. This explorative study investigated child exposure to OPs and PYRs, comparing temporal and spatial exposure variability within and among urine, wristbands, and dust samples. METHODS: During spraying season 2018, 38 South African children in two agricultural areas (Grabouw/Hex River Valley) and settings (farm/village) participated in a seven-day study. Child urine and household dust samples were collected on days 1 and 7. Children and their guardians were wearing silicone wristbands for seven days. Intraclass correlation coefficients (ICCs) evaluated temporal agreements between repeated urine and dust samples, Spearman rank correlations (Rs) evaluated the correlations among matrices, and linear mixed-effect models investigated spatial exposure predictors. A risk assessment was performed using reverse dosimetry. RESULTS: Eighteen OPs/PYRs were targeted in urine, wristbands, and dust. Levels of chlorpyrifos in dust (ICC = 0.92) and diethylphosphate biomarker in urine (ICC = 0.42) showed strong and moderate temporal agreement between day 1 and day 7, respectively. Weak agreements were observed for all others. There was mostly a weak correlation among the three matrices (Rs = -0.12 to 0.35), except for chlorpyrifos in dust and its biomarker 3,5,6-trichloro-2-pyridinol in urine (Rs = 0.44). No differences in exposure levels between living locations were observed. However, 21% of the urine biomarker levels exceeded the health-risk threshold for OP exposure. CONCLUSIONS: Observed high short-term variability in exposure levels during spraying season highlights the need for repeated sampling. The weak correlation between the exposure matrices points to different environmental and behavioral exposure pathways. Exceeding risk thresholds for OP should be further investigated.
- Publikační typ
- časopisecké články MeSH
Mycobacterium tuberculosis is responsible for tuberculosis (TB) all over the world. Despite tremendous advancements in biomedical research, new treatment approaches, and preventive measures, TB incidence rates continue to ascend. The herbaceous plant Acalypha indica, also known as Indian Nettle, belongs to the Euphorbiaceae family and is known as one of the most important sources of medicines and pharmaceuticals for the medical therapy for a range of ailments. However, the precise molecular mechanism of its therapeutic action is still unknown. In this study, an integrated network pharmacology approach was employed to explore the potential mechanism of A. indica phytochemicals against TB. The active chemical components of A. indica were collected from two independent databases and published sources, whereas SwissTargetPrediction was used to identify the target genes of these phytochemicals. GeneCards and DisGeNET databases were employed to retrieve tuberculosis-related genes and variants. Following the evaluation of overlapped genes, gene enrichment analysis and PPI network analysis were performed using the DAVID and STRING databases, respectively. Later, to identify the potential target(s) for the disease, molecular docking was performed. A. indica revealed 9 active components with 259 potential therapeutic targets; TB attributed 694 intersecting genes from the two data sets; and both TB and A. indica overlapped 44 potential targets. The in-depth analysis based on the degree revealed that AKT1 and EGFR formed the foundation of the PPI network. Moreover, docking analysis followed by molecular dynamics simulations revealed that phytosterol and stigmasterol have higher binding affinities to AKT1 and EGFR to suppress tuberculosis. This study provides a convincing proof that A. indica can be exploited to target TB after experimental endorsement; further, it lays the framework for more experimental research on A. indica's anti-TB activity.
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND HYPOTHESIS: Hospital admissions in pediatric dialysis patients need to be better studied, and most existing studies are retrospective and based on registry data. This study aimed to analyse and compare hospital admission rates, causes, length of stay (LOS), and outcomes in children treated with peritoneal dialysis (PD) and hemodialysis (HD). METHODS: Data from 236 maintenance PD and 138 HD patients across 16 European dialysis centers were collected between 1 July 2017 and 30 June 2018. A total of 178 hospitalized patients (103 PD, 75 HD) were included for further analyses. RESULTS: There were 465 hospitalization events (268 PD, 197 HD) with a rate of 0.39 admissions per 100 patient-days at risk (PDAR) and 2.4 hospital days per 100 PDAR. The admission rates were not significantly different between HD and PD patients. The most common causes of hospitalization were access-related infections (ARI) (17%), non-infectious complications of access (NIAC) (14%), and infections unrelated to access (12%). ARI was the leading cause in PD patients (24%), while NIAC was more common in HD patients (19%). PD patients had more ARIs, diagnostic procedures, and treatment adjustments (P < .05), while HD patients had more NIACs, infections unrelated to access, access placement procedures, and interventional/surgical procedures (P < .001). LOS was longer with acute admissions than non-acute admissions (P < .001). Overall LOS and LOS in the intensive care unit were similar between HD and PD patients. High serum uric acid and low albumin levels were significant predictors of longer LOS (P = .022 and P = .045, respectively). Young age, more significant height deficit, and older age at the start of dialysis were predictors of longer cumulative hospital days (P = .002, P = .001, and P = .031, respectively). CONCLUSION: Access-related complications are the main drivers of hospitalization in pediatric dialysis patients, and growth and nutrition parameters are significant predictors of more extended hospital stays.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype. METHODS: We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines. RESULTS: According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P=0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P=0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis. CONCLUSIONS: We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.
- MeSH
- adrenergní látky MeSH
- ateroskleróza * komplikace MeSH
- fenotyp MeSH
- feochromocytom * diagnóza MeSH
- infarkt myokardu * MeSH
- kardiomyopatie * MeSH
- katecholaminy MeSH
- lidé MeSH
- metanefrin MeSH
- nádory nadledvin * patologie MeSH
- paragangliom * komplikace MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
3,5-Dinitrobenzylsulfanyl tetrazoles and 1,3,4-oxadiazoles, previously identified as having high in vitro activities against both replicating and nonreplicating mycobacteria and favorable cytotoxicity and genotoxicity profiles were investigated. First we demonstrated that these compounds act in a deazaflavin-dependent nitroreduction pathway and thus require a nitro group for their activity. Second, we confirmed the necessity of both nitro groups for antimycobacterial activity through extensive structure-activity relationship studies using 32 structural types of analogues, each in a five-membered series. Only the analogues with shifted nitro groups, namely, 2,5-dinitrobenzylsulfanyl oxadiazoles and tetrazoles, maintained high antimycobacterial activity but in this case mainly as a result of DprE1 inhibition. However, these analogues also showed increased toxicity to the mammalian cell line. Thus, both nitro groups in 3,5-dinitrobenzylsulfanyl-containing antimycobacterial agents remain essential for their high efficacy, and further efforts should be directed at finding ways to address the possible toxicity and solubility issues, for example, by targeted delivery.
- MeSH
- antituberkulotika farmakologie chemie MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium tuberculosis * MeSH
- nitroreduktasy MeSH
- oxadiazoly farmakologie chemie MeSH
- savci MeSH
- tetrazoly farmakologie chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In recent years, several international urological societies have published guidelines on the diagnosis, treatment, and follow-up of urethral strictures, but a guideline for the German-speaking region has not been available to date. This summary provides a detailed comparison of the guidelines of the European Association of Urology (EAU), American Urological Association (AUA) and the Société Internationale d'Urologie (SIU) with regard to the treatment of anterior urethral strictures, i.e. from the bulbar urethra to the meatus. In the following work, differences and specific recommendations in the guidelines are highlighted. In particular, the three guidelines largely agree with regard to diagnostic workup and follow-up. However, divergences exist in the management of anterior urethral strictures, particularly with regard to the use of endoscopic therapeutic approaches and the use of urethral stents. In addition, the EAU provides more comprehensive and detailed recommendations on urethroplasty techniques and specific patient follow-up. The EAU guidelines are the most current and were the first to include instructions for urethral strictures in women and individuals with gender incongruence after genital approximation surgery. Reconstructive urology is a rapidly evolving specialty and, thus, the clinical approach has been changing accordingly. Although guideline recommendations have become more inclusive and comprehensive, more high-quality data are needed to further improve the level of evidence.
- MeSH
- lidé MeSH
- správnost dat MeSH
- striktura uretry * diagnóza MeSH
- uretra chirurgie MeSH
- urologie * MeSH
- zákroky plastické chirurgie * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Spojené státy americké MeSH
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory očního víčka * chirurgie patologie MeSH
- oftalmologické chirurgické výkony * metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- pseudoblefaroptóza,
- MeSH
- blefaroptóza * diagnóza patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci očních víček * chirurgie diagnóza patologie MeSH
- oftalmologické chirurgické výkony metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- benigní pemfigoid sliznice * diagnostické zobrazování farmakoterapie patologie MeSH
- cyklofosfamid aplikace a dávkování MeSH
- hyperemie farmakoterapie MeSH
- kombinovaná farmakoterapie MeSH
- kyselina mykofenolová aplikace a dávkování MeSH
- lidé MeSH
- nemoci spojivky * diagnostické zobrazování farmakoterapie patologie MeSH
- prednisolon aplikace a dávkování MeSH
- rituximab aplikace a dávkování MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- glukokortikoidy aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanom * chirurgie diagnóza farmakoterapie patologie MeSH
- mitomycin aplikace a dávkování MeSH
- nádory spojivky * chirurgie diagnóza farmakoterapie patologie MeSH
- poruchy pigmentace etiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH