The endorsement of conspiracy theories may be increased by subjectively perceived stress. Yet, it is not known whether this correlation is caused by the effects of the acute stress reaction on the brain or other psychological, social, or methodological factors. The effect of an experimentally induced acute stress reaction on conspiracy thinking was tested on a sample (n = 115) of students of medicine. Although the stress procedure caused a substantial increase in salivary cortisol, there was no significant effect on endorsing conspiracy theories or adopting conspiracy interpretations of novel information. The results confirmed no effect of the acute stress reaction on conspiracy thinking, suggesting it may be absent or weaker than expected. The study demonstrated the viability of psychophysiological experimental design in conspiracy research and may inspire further examination of the physiological mechanisms underlying susceptibility to conspiracy theories.
- MeSH
- Adult MeSH
- Hydrocortisone analysis metabolism MeSH
- Humans MeSH
- Young Adult MeSH
- Stress, Psychological * psychology MeSH
- Saliva chemistry MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Mineralocorticoid receptor antagonists (MRA) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF) but are underused in clinical practice. Observational data suggest that hyperkalemia is the leading obstacle for the suboptimal use of MRA. OBJECTIVES: This study sought to evaluate the effects of sodium zirconium cyclosilicate (SZC) in optimizing use of spironolactone among participants with HFrEF and hyperkalemia. METHODS: REALIZE-K (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone) was a prospective, double-blind, randomized- withdrawal trial in participants with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal guideline-directed therapy (except MRA), and prevalent or incident MRA-induced hyperkalemia. During open-label run-in, participants underwent spironolactone titration (target: 50 mg/day); those with hyperkalemia started SZC. Participants with normokalemia (potassium: 3.5-5.0 mEq/L) on SZC and spironolactone ≥25 mg/day were randomized to continued SZC or placebo for 6 months. The primary endpoint was optimal treatment response (normokalemia on spironolactone ≥25 mg/day without rescue therapy for hyperkalemia [months 1-6]). The 5 secondary endpoints were tested hierarchically. Exploratory endpoints included a composite of adjudicated cardiovascular death or worsening heart failure (HF) events (hospitalizations and urgent visits). RESULTS: Overall, 203 participants were randomized (SZC: 102; placebo: 101). Higher percentage of SZC- vs placebo-treated participants had optimal response (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; P < 0.001). SZC (vs placebo) improved the first 4 secondary endpoints: normokalemia on randomization dose of spironolactone and without rescue therapy (58% vs 23%; OR: 4.58; 95% CI: 2.78-7.55; P < 0.001); receiving spironolactone ≥25 mg/day (81% vs 50%; OR: 4.33; 95% CI: 2.50-7.52; P < 0.001); time to hyperkalemia (HR: 0.51; 95% CI: 0.37-0.71; P < 0.001); and time to decrease/discontinuation of spironolactone due to hyperkalemia (HR: 0.37; 95% CI: 0.17-0.73; P = 0.006). There was no between-group difference in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at 6 months (-1.01 points; 95% CI: -6.64 to 4.63; P = 0.72). Adverse events (64% vs 63%) and serious adverse events (23% vs 22%) were balanced between SZC and placebo, respectively. Composite of cardiovascular (CV) death or worsening HF occurred in 11 (11%) participants in the SZC group (1 with CV death, 10 with HF events) and 3 (3%) participants in the placebo group (1 with CV death, 2 with HF events; log-rank nominal P = 0.034). CONCLUSIONS: In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalemia and down-titration/discontinuation of spironolactone. Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone; NCT04676646).
- MeSH
- Mineralocorticoid Receptor Antagonists * therapeutic use administration & dosage adverse effects MeSH
- Double-Blind Method MeSH
- Hyperkalemia * drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Prospective Studies MeSH
- Aged MeSH
- Silicates * therapeutic use administration & dosage adverse effects MeSH
- Spironolactone * administration & dosage adverse effects therapeutic use MeSH
- Heart Failure * drug therapy MeSH
- Stroke Volume drug effects physiology MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. RESULTS: A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. CONCLUSIONS: Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).
- MeSH
- C-Reactive Protein * analysis MeSH
- Stroke prevention & control MeSH
- Double-Blind Method MeSH
- Myocardial Infarction * prevention & control mortality MeSH
- Kaplan-Meier Estimate MeSH
- Colchicine * therapeutic use adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Recurrence MeSH
- Secondary Prevention MeSH
- Aged MeSH
- Spironolactone therapeutic use adverse effects MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed. RESULTS: We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P = 0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P = 0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group. CONCLUSIONS: Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure. (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).
- MeSH
- Mineralocorticoid Receptor Antagonists * therapeutic use adverse effects MeSH
- Stroke mortality MeSH
- Double-Blind Method MeSH
- Myocardial Infarction * mortality drug therapy MeSH
- Kaplan-Meier Estimate MeSH
- Cardiovascular Diseases mortality prevention & control MeSH
- Percutaneous Coronary Intervention MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Spironolactone * therapeutic use adverse effects MeSH
- Heart Failure * drug therapy mortality MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Pseudohypoaldosteronism type 2 (PHA2) is a rare inherited condition of altered tubular salt handling. It is characterized by the specific constellation of hyperkalaemic hyporeninemic hypertension, hyperchloremic metabolic acidosis and hypercalciuria. Molecular genetic testing confirms the diagnosis in the majority of cases. Thiazides constitute effective treatment. Due to its rarity, the diagnosis is often delayed. We here present two children with PHA2, who were initially treated with fludrocortisone and bicarbonate complicated mainly by exacerbation of their hypertension. Discontinuation of their previous therapy and commencement of thiazide diuretics led to normalisation of their blood pressure and electrolyte and acid-base status.
- MeSH
- Acidosis * diagnosis etiology MeSH
- Child MeSH
- Fludrocortisone therapeutic use MeSH
- Hyperkalemia diagnosis etiology genetics blood MeSH
- Hypertension * diagnosis etiology drug therapy genetics MeSH
- Sodium Chloride Symporter Inhibitors therapeutic use MeSH
- Blood Pressure MeSH
- Humans MeSH
- Pseudohypoaldosteronism * genetics diagnosis physiopathology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
AIM: Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity. METHODS: In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before. RESULTS: Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population. CONCLUSIONS: A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty.
- MeSH
- 17-alpha-Hydroxyprogesterone * blood MeSH
- False Negative Reactions MeSH
- Adrenal Hyperplasia, Congenital * diagnosis blood MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Neonatal Screening * methods MeSH
- Steroid 21-Hydroxylase genetics MeSH
- Age of Onset MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Poznatky, získané hlavne v posledných dvoch desaťročiach, umožnili lepšie porozumieť mechanizmom a dráham, prostredníctvom ktorých nervový systém, a tým aj stres, ovplyvňuje procesy súvisiace so vznikom a progresiou nádorových chorôb. Neurobiologický výskum nádorových chorôb pritom nie len rozšíril poznanie etiopatogenézy nádorového procesu, ale vytvoril podklady aj pre zavedenie nových terapeutických metód v onkológii, založených na modulácii prenosu signálov medzi nervovým systémom a nádorovým tkanivom. Bolo tiež zistené, že monitorovanie aktivity zložiek autonómneho nervového systému je možné využiť nie len na určenie miery stresu u daného pacienta, ale aj na posúdenie prognózy jeho onkologickej choroby. Jednu z efektívnych metód, umožňujúcich sledovanie flexibility a rovnováhy pôsobenia zložiek autonómneho nervového systému a nepriamo aj miery stresu u onkologických pacientov, predstavuje určovanie variability srdcovej frekvencie (HRV). Na opodstatnenosť využitia tejto metódy v onkológii poukazujú aj zistenia, že pacienti s vyššími hodnotami HRV vykazujú dlhšie prežívanie v porovnaní s pacientmi, u ktorých sú hodnoty HRV nižšie. Zámerom tohto textu je priblížiť súčasné poznatky týkajúce sa vplyvu stresu na nádory hlavy a krku a načrtnúť možnosti využitia stanovenia HRV ako prognostického markera u týchto pacientov. Diskutované sú aj možnosti využitia metód, ktoré sú zamerané na zvýšenie HRV a ich prípadné využitie v liečbe pacientov s nádormi hlavy a krku.
Knowledge, mainly gained in the last two decades, has provided a better understanding of the mechanisms and pathways through which the nervous system, and thus stress, influences processes related to cancer initiation and progression. Neurobiological research on cancer has not only increased the knowledge of the aetiopathogenesis of the tumour process, but also has laid the foundation for the introduction of new therapeutic methods in oncology based on the modulation of the transmission of signals between the nervous system andtumour tissue. It also has been found that monitoring the activity of components of the autonomic nervous system can be used not only to determine the degree of stress in a given patient, but also to assess the prognosis of his or her oncological disease. One of the effective methods to monitor the flexibility and balance of the autonomic nervous system components and indirectly the level of stress in cancer patients is the determination of heart rate variability (HRV). The validity of the use of this method in oncology is indicated by the findings that patients with higher HRV values show longer survival compared to patients with lower HRV values. The aim of this text is to review the current knowledge regarding the impact of stress on head and neck cancer and to outline the possibilities of using HRV determination as a prognostic marker in these patients. The potential use of methods aimed at increasing HRV and their potential use in the management of patients with head and neck tumours are also discussed.
Fibrilácia predsiení (FP) je najčastejšia arytmia v klinickej praxi prispievajúca k zvýšenej morbidite a mortalite. Humorálne biomarkery, ako natriuretické peptidy, troponín, aldosterón, kortizol, kopeptín a apelín, zohrávajú čoraz dôležitejšiu úlo- hu v diagnostike, predikcii prognózy a manažmente FP. Zvýšené hladiny týchto biomarkerov naznačujú nielen poruchu funkcie myokardu a remodeláciu predsiení, ale aj zápalové a prokoagulačné stavy, ktoré ovplyvňujú vývoj a komplikácie FP. Sledovanie hladín biomarkerov poskytuje hlbší náhľad na patofyziologické mechanizmy FP a môže pomôcť pri identi- fikácii pacientov so zvýšeným rizikom komplikácií, ako sú tromboembolické príhody alebo progresia ochorenia. Integrácia biomarkerov do klinickej praxe môže výrazne zlepšiť stratifikáciu rizika, umožniť personalizovanejší prístup k liečbe FP a prispieť k efektívnejšiemu monitorovaniu priebehu ochorenia. Dôkazy o spojitosti medzi biomarkermi a FP sú povzbud- zujúce, avšak sú potrebné ďalšie štúdie na potvrdenie ich klinického využitia v štandardnej starostlivosti o pacientov s týmto závažným ochorením.
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, contributing to increased morbidity and mortality. Humoral biomarkers, such as natriuretic peptides, troponin, aldosterone, cortisol, copeptin, and apelin, are gaining importance in the diagnosis, prognosis, and management of AF. Elevated levels of these biomarkers indicate not only myocardial dysfunction and atrial remodeling but also inflammatory and procoagulant states that influence the progression and complications of AF. Monitoring biomarker levels provides deeper insight into the pathophysiological mechanisms of AF and can aid in identifying patients at higher risk of complications, such as thromboembolic events or disease progression. Integrating biomarkers into clinical practice can significantly improve risk stratification, facilitate a more personalized approach to AF treatment, and contribute to more effective disease monitoring. Evidence linking biomarkers with AF is promising; however, further studies are needed to confirm their clinical utility in standard care for patients with this serious condition.
- MeSH
- Aldosterone MeSH
- Apelin MeSH
- Arginine Vasopressin MeSH
- Biomarkers MeSH
- Atrial Fibrillation * diagnosis MeSH
- Hydrocortisone MeSH
- Humans MeSH
- Natriuretic Peptides MeSH
- Troponin blood MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
LIM and Src homology 3 (SH3) protein 2 (LASP2) is a small focal adhesion protein first identified as a splice variant of the nebulette gene (Nebl). As the newest member of the nebulin protein family, the regulation and function of LASP2 remain largely unknown. Our previous RNA-sequencing results identified Nebl as one of the most highly induced genes in the mouse liver in response to the activation of pregnane X receptor (PXR). In this study, we investigated this phenomenon further and show that PXR induces Lasp2 instead of Nebl, which partially use the same exons. Lasp2 was found to be induced in response to PXR ligand pregnenolone 16α-carbonitrile (PCN) treatment in mouse liver in vivo both after 4-day treatment and after long-term, 28-day treatment and in both male and female mice. Interestingly, the Lasp2 induction was more efficient in high-fat diet-fed mice (103-fold after 4-day PCN treatment) than in the normal chow-fed mice (32-fold after 4-day PCN treatment). Lasp2 induction was abolished in PXR knockout mice but could be rescued by re-expression of PXR, indicating that Lasp2 induction is PXR mediated. In mouse primary hepatocytes cycloheximide did not inhibit Lasp2 induction by PCN and a PXR binding site could be recognized upstream of the mouse Lasp2 gene suggesting direct regulation of Lasp2 by PXR. In human 3D hepatocytes, rifampicin induced only a modest increase in LASP2 expression. This study shows for the first time that PXR activation strongly induces Lasp2 expression in mouse liver and establishes Lasp2 as a novel PXR target gene. SIGNIFICANCE STATEMENT: RNA-sequencing results have previously identified nebulette (Nebl) to be efficiently induced by pregnane X receptor activating compounds. This study shows that instead of Nebl, LIM and Src homology 3 (SH3) protein 2 (Lasp2) coding for a small focal adhesion protein and partly sharing exons with the Nebl gene is a novel target of pregnane X receptor in mouse liver.
- MeSH
- Adaptor Proteins, Signal Transducing genetics metabolism MeSH
- Cytoskeletal Proteins * genetics metabolism MeSH
- Hepatocytes metabolism drug effects MeSH
- Liver * metabolism drug effects MeSH
- Humans MeSH
- Mice, Inbred C57BL * MeSH
- Mice, Knockout * MeSH
- Mice MeSH
- Pregnane X Receptor * genetics metabolism MeSH
- Pregnenolone Carbonitrile pharmacology MeSH
- LIM Domain Proteins * genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
