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

Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

• MeSH
• Anti-Inflammatory Agents pharmacology   chemistry   MeSH
• Dexamethasone * pharmacology   chemistry   analogs & derivatives   MeSH
• Liver * drug effects   metabolism   MeSH
• Polylactic Acid-Polyglycolic Acid Copolymer * chemistry   MeSH
• Macrophages * drug effects   metabolism   MeSH
• Mice MeSH
• Nanospheres * chemistry   MeSH
• Drug Carriers chemistry   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals 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

Fructobacillus, a Gram-positive, non-spore-forming, facultative anaerobic bacterium, belongs to the fructophilic lactic acid bacteria (FLAB) group. The group's name originates from fructose, the favored carbon source for its members. Fructobacillus spp. are noteworthy for their distinctive traits, captivating the interest of scientists. However, there have been relatively few publications regarding the isolation and potential utilization of these microorganisms in the industry. In recent years, F. tropaeoli has garnered interest for its promising role in the food and pharmaceutical sectors, although the availability of isolates is rather limited. A more comprehensive understanding of Fructobacillus is imperative to evaluate their functionality in the industry, given their unique and exceptional properties. Our in vitro study on Fructobacillus tropaeoli KKP 3032 confirmed its fructophilic nature and high osmotolerance. This strain thrives in a 30% sugar concentration, shows resistance to low pH and bile salts, and exhibits robust autoaggregation. Additionally, it displays significant antimicrobial activity against foodborne pathogens. Evaluating its probiotic potential, it aligns with EFSA recommendations in antibiotic resistance, except for kanamycin, to which it is resistant. Further research is necessary, but preliminary analyses confirm the high probiotic potential of F. tropaeoli KKP 3032 and its ability to thrive in the presence of high concentrations of fructose. The results indicate that the isolate F. tropaeoli KKP 3032 could potentially be used in the future as a fructophilic probiotic, protective culture, and/or active ingredient in fructose-rich food.

• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Fructose metabolism   MeSH
• Hydrogen-Ion Concentration MeSH
• Fruit and Vegetable Juices * microbiology   MeSH
• Citrus sinensis microbiology   chemistry   MeSH
• Food Microbiology MeSH
• Probiotics * isolation & purification   MeSH
• RNA, Ribosomal, 16S genetics   MeSH
• Bile Acids and Salts metabolism   MeSH
• Publication type
• Journal Article 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

BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.

• MeSH
• Androstenes MeSH
• Androgen Receptor Antagonists * adverse effects   therapeutic use   MeSH
• Benzamides adverse effects   MeSH
• Phenylthiohydantoin MeSH
• Cardiovascular Diseases * chemically induced   epidemiology   MeSH
• Humans MeSH
• Prostatic Neoplasms * drug therapy   pathology   MeSH
• Nitriles adverse effects   MeSH
• Randomized Controlled Trials as Topic MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Network Meta-Analysis MeSH
• Systematic Review MeSH

Atherosclerosis is a chronic inflammatory disease of the blood vessels caused by elevated levels of lipoproteins. The hyperlipoproteinemia triggers a series of cellular changes, particularly the activation of the macrophages, which play a crucial role in the development and progression of atherosclerosis. The presence of free cholesterol (FC) in lipoproteins may contribute to macrophage stimulation. However, the mechanisms linking the accumulation of FC in macrophages to their pro-inflammatory activation remain poorly understood. Our research found a positive correlation between the number of pro-inflammatory macrophages (CD14 + CD16 + CD36high) in visceral adipose tissue and the levels of LDL-C and cholesterol remnant particles in 56 healthy people. In contrast, the proportion of anti-inflammatory, alternatively activated macrophages (CD14 + CD16-CD163+) correlated negatively with HDL-C. Additionally, our in vitro study demonstrated that macrophages accumulating FC promoted a pro-inflammatory response, activating the TNF-α and chemokine CCL3 genes. Furthermore, the accumulation of FC in macrophages alters the surface receptors on macrophages (CD206 and CD16) and increases cellular granularity. Notably, the CD36 surface receptor and the ACAT and CD36 genes did not show a response. These results suggest a link between excessive FC accumulation and systemic inflammation to underlie the development of atherosclerosis.

• MeSH
• Macrophage Activation MeSH
• CD36 Antigens metabolism   MeSH
• Atherosclerosis metabolism   MeSH
• Antigens, CD metabolism   MeSH
• Cholesterol * metabolism   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Macrophages * metabolism   immunology   drug effects   MeSH
• Intra-Abdominal Fat metabolism   MeSH
• Tumor Necrosis Factor-alpha metabolism   genetics   MeSH
• Inflammation * metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH