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A healthy 26-year-old patient presented a primary herpetic type 2 infection. The infection disseminated to the skin, the mucosa and the liver. The clinical course of the infection had a favorable issue.
Sera from 173 healthy adults and 55 rheumatoid patients were studied for IgG-, IgM- and IgA-rheumatoid factors (RFs) by a modification of Este's indirect immunofluorescence method. Rabbit IgG bound to smeared sheep red cells was used as antigen. With each serum tested a smear on non-sensitized cells was used as control antigen. Anti-IgG of the sera studied, binding to the antigen, was demonstrated by fluorescein-conjugated antisera, monospecific for gamma, mu and alpha chains, and not containing antibodies to sheep erythrocytes or rabbit IgG. Positive reactions were obtained with IgG as antigen, but not with the F(ab')2 fragment. The sera tested were treated with dithiothreitol before they were assayed for IgG-RF, in order to abolish false-positive reactions due to IgM-RF activity. The detection limit for IgM-RF was 1 IU per ml. IgM-RF titres of 9 occurred in 7% of healthy adults and 73% of rheumatoid patients, titres greater than or equal to 18 in 3.5% and 67% respectively. IgG-RF titres of 9 occurred in 9% of healthy adults, 21% of seronegative and 24% of seropositive rheumatoid patients. Titres of 18 occurred in 3% of healthy adults and in 14% of seronegative rheumatoid patients. Titres of greater than or equal to 18 occurred in 22% of seropositive rheumatoid patients. IgG-RF was correlated with an involvement of more than 20 joints. IgA-RF was found in 83% of seropositive, 11% of seronegative rheumatoid patients and in none of the healthy adults (serum dilution 1:9).
TSH, T3 and T4 response to stimulation with thyrotropin releasing hormone (TRH) has been investigated in 24 young healthy adults after intravenous injection and in 25 young healthy adults upon oral application of 40 mg of TRH. After intravenous injection the TSH concentration raises from a mean of 1.6 to a mean maximum of 11.7 muU/ml. A statistically significant sex difference could not be found. T3 shows a statistically significant increase which is however too small to be of diagnostic value in an individual test. After oral stimulation with 40 mg of TRH, TSH rises to a slightly higher maximum of 13.2 muU/ml after 3 h. The T3 increase from 1.5 to 2.19 ng/ml is significant and considerably higher than after intravenous stimulation. The thyroxin increase is statistically significant. The present results compare well with previously published data for intravenous stimulation. The oral route of TRH application has not yet been widely used and the present series establishes the normal response in young healthy adults. Repetitive stimulation with three times 40 mg of TRH leads to a decrease in TSH stimulation which reaches 5.8 muU/ml 3 h after the third dose. This is in contrast to a comparable increase in plasma T3.
BACKGROUND: Psychedelic microdosing has gained increasing popularity for enhancing mood and cognition, yet its effects on psychological outcomes in healthy adults remain unclear. We aim to evaluate the efficacy and safety of psychedelic microdosing on psychological outcomes in healthy/non-clinical adult population. METHODS: This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251035294). We searched Embase, MEDLINE, and PsycINFO from inception to February 2026 for original studies in healthy adults using sub-hallucinogenic psychedelic doses on separate days. We included randomized studies, nonrandomized prospective studies, cross-sectional studies, and observational longitudinal designs and stratified meta-analyses by design. Random-effects models were used; safety in randomized controlled trials (RCTs) was pooled as risk differences (RDs). Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. RESULTS: 24 studies (3,681 participants) met inclusion criteria, 6 contributed to meta-analyses. RCTs of psilocybin and LSD microdosing showed subjective and neurophysiological effects but minimal impact on cognition, creativity, or sustained mood. Psilocybin altered EEG and speech with little behavioral change, while LSD caused transient mood and minor physiological effects without lasting cognitive or personality benefits. Observational studies indicated mood and personality improvements, likely influenced by expectancy or lifestyle factors. Meta-analyses included two parallel RCTs (3 comparisons; n = 117) and three non-RCT studies (n = 1,013). Adverse event analyses included two RCTs (4 comparisons; n = 109). RCTs showed no clear evidence of immediate symptom reduction: depressive symptoms (SMD = -0.19; 95% CI -0.56, 0.19; I2 = 0%), anxiety (SMD = -0.20; 95% CI -1.11, 0.71; I2 = 82.3%),and stress (SMD = 0.02; 95% CI -0.39, 0.43; I2 = 0%). Non-RCT within-arm estimates were imprecise and heterogeneous for depressive symptoms (SMCC -0.33; 95% CI -0.75, 0.08) and anxiety (SMCC -0.29; 95% CI-0.84, 0.26). Exploratory pooling across all designs suggested decreases in depressive symptoms and stress, while anxiety remained uncertain. Adverse event risks were similar between treatment and control. CONCLUSIONS: Microdosing does not show consistent immediate benefits for depressive, anxiety, or stress symptoms in healthy adults, and evidence from RCTs remains inconclusive. Although improvements were observed in some studies, these effects were not significantly different from placebo. Larger, well-designed RCTs are needed to clarify the efficacy and safety of psychedelic microdosing beyond placebo.
BACKGROUND: Benefits of sensory-training interventions on sensorimotor outcomes are inconsistent, and it is unclear whether transcranial direct current stimulation (tDCS) can enhance proprioception, which is fundamental to neuromuscular control. Existing evidence is dominated by upper-limb studies, so transferability to the knee is unclear. This study investigated whether a single session of anodal high-definition (HD)-tDCS, alone or combined with brief two-point discrimination (TPD) training, enhances knee sensorimotor function and performance in healthy adults. METHODS: In a double-blind randomised-controlled trial, 57 healthy participants received (1) 20-min, 1 mA anodal HD-tDCS over the knee primary somatosensory (S1) map or sham stimulation, and (2) 15-min knee TPD training or no training. Knee somatosensory, sensorimotor, and functional performance measures were assessed pre- and immediately post-intervention. Three-way mixed-design ANOVAs, equivalence testing (smallest effect size of interest η2 = 0.02), Bayes factors, and linear mixed-effects models quantified effects. RESULTS: HD-tDCS, TPD training, and their sequential combination had no effect on any outcome measure (p ≥ 0.05; η2 ≤ 0.015). Confidence intervals spanned equivalence bounds, and equivalence testing results were non-significant (p ≥ 0.05). Bayes factors (<0.33) showed moderate evidence for the null (no effect). Mixed-effects modelling attributed ≤8% of total variance to intervention fixed effects, with the remainder captured by participant-level random effects. CONCLUSION: A single 20-minute session of 1 mA HD-tDCS, with or without brief TPD training, does not acutely modify knee somatosensory, sensorimotor, or functional performance in healthy adults. Existing evidence at the hand may not translate to the lower limb. Future work should investigate higher-dose, multi-session, task-concurrent, or network-targeted strategies in clinical populations.
Bioequivalence and safety of ADL-018, an omalizumab biosimilar, were compared with United States-licensed omalizumab (US-OMA) and European Union-approved omalizumab (EU-OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL-018, US-OMA, or EU-OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC(0-last), AUC(0-∞), and Cmax, were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80-1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n = 102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL-018 vs US-OMA: AUC(0-last)-1.08, AUC(0-∞)-1.07, Cmax-1.05; GMRs of ADL-018 vs EU-OMA: AUC(0-last)-1.06, AUC(0-∞)-1.06, Cmax - 1.05; and GMRs of US-OMA vs EU-OMA: AUC(0-last)-0.99, AUC(0-∞)-0.99, Cmax-1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC ∼30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC ∼29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment-emergent adverse events: ADL-018, n = 6; US-OMA, n = 5; EU-OMA, n = 4) was observed. ADL-018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.
BACKGROUND: The OPTIMAL (Optimizing Performance Through Intrinsic Motivation and Attention for Learning) theory is a motor learning framework proposing that optimizing intrinsic motivation enhances motor performance and learning. The theory identifies three key components-Enhanced Expectancies (EE), Autonomy Support (AS) and External Focus of Attention (EF)-which facilitate more efficient, goal-directed movement. These components have been shown to improve motor outcomes in limb-based tasks; however, their application to respiratory training, particularly in clinical contexts such as voice and swallowing therapy in patients with Parkinson's disease (pwPD), has not yet been systematically explored. AIMS: This study aimed to investigate whether implementing OPTIMAL theory strategies during a respiratory muscle strength training (RMST) task improves immediate respiratory motor performance in healthy adults and pwPD. Additionally, we aimed to examine the effects of these strategies on motivation and cognitive engagement. METHODS: This quasi-randomized, single-session trial included 47 participants: Healthy CONTROL (n = 17), Healthy OPTIMAL (n = 16) and PD OPTIMAL (n = 14). Healthy participants were quasi-randomly assigned to either intervention or control conditions, whereas pwPD completed the intervention only. All participants completed a single respiratory session that included baseline, practice and retention phases. Outcome measures included peak expiratory flow, cough peak expiratory flow, cognitive engagement (EEG-based Cognitive Engagement Index) and self-administered motivation questionnaire. OUTCOMES AND RESULTS: Exhalation force improved from baseline to retention in the Healthy OPTIMAL group (baseline: M = 296 L/min; retention: M = 338 L/min; p < 0.001) and the PD OPTIMAL group (baseline: M = 315 L/min; retention: M = 370 L/min; p < 0.0001), but not in the Healthy CONTROL group (p > 0.05). No significant changes in cough strength were observed in any group. No correlations were found between cognitive engagement and exhalation force or motivation scores. However, motivation increased more in the Healthy OPTIMAL group (Questionnaire 1: M = 57.2; Questionnaire 2: M = 60.7) and the PD OPTIMAL group (Questionnaire 1: M = 60.1; Questionnaire 2: M = 62.8) than in the Healthy CONTROL group (Questionnaire 1: M = 61.1; Questionnaire 2: M = 62.5). CONCLUSIONS AND IMPLICATIONS: Implementing the OPTIMAL theory enhances immediate respiratory motor performance in both healthy participants and pwPD. OPTIMAL theory has clinical value in voice and swallowing therapy, although further research is needed to establish long-term efficacy and clinical impact. WHAT THIS PAPER ADDS: What is already known on the subject Motivation is a critical factor in rehabilitation. The OPTIMAL theory has been shown to improve both motivation and motor performance in limb-based tasks. Its impact on respiratory training, however, has not been previously examined. What this paper adds to the existing knowledge This study shows that applying OPTIMAL strategies during a respiratory muscle strength training task significantly improved peak expiratory flow in both healthy adults and people with Parkinson's disease. What are the potential or clinical implications of this work? Integrating the OPTIMAL theory principles into respiratory therapy may enhance motor outcomes, supporting voice, swallowing and cough rehabilitation.
While probiotics are increasingly consumed for health benefits, comprehensive safety assessments, particularly for novel strains, are imperative. This study aimed to conduct a holistic safety and efficacy assessment of Bifidobacterium longum subsp. infantis (B. infantis) BI45, spanning genomic analysis, in vitro tests, In vivo toxicity test, and a clinical trial. The safety of B. infantis BI45 was evaluated through: (1) whole-genome sequencing for antibiotic resistance and virulence genes; (2) in vitro phenotyping (hemolysis, cytotoxicity, gastrointestinal tolerance and antibiotic susceptibility); (3) an acute oral toxicity study in mice; and (4) a randomized, double-blind, placebo-controlled clinical trial. Forty-eight healthy adults were recruited and randomly assigned to receive either B. infantis BI45 or a placebo (n = 24/group) for 8 weeks. Hematological, biochemical, immunological, and gut microbiota parameters were assessed. Genomic analysis identified no transferable antibiotic resistance or virulence genes. In vitro assays confirmed the absence of hemolytic and cytotoxic activity, alongside high gastrointestinal tolerance. Antibiotic susceptibility testing showed that B. infantis BI45 is sensitive to a range of antibiotics. No adverse effects were observed in the murine toxicity study at 2 × 10¹⁰ CFU/kg. Importantly, the clinical intervention revealed no adverse events or significant alterations in hematological, hepatic, or renal function markers in the B. infantis BI45 group, demonstrating an excellent safety profile. Furthermore, B. infantis BI45 supplementation significantly increased serum levels of immunomodulatory markers Immunoglobulin A (IgA) and antimicrobial peptide LL-37 compared to the placebo (p < 0.05) and modulated the gut microbiota by enriching beneficial short-chain fatty acid producers. The multi-tiered evidence demonstrates that B. infantis BI45 is a safe probiotic strain that does not induce adverse reactions in healthy adults. Its consumption positively modulates host immunity and the gut microbiota.Trial Registration Number: NCT06863415 (ClinicalTrials.gov).
Two previously healthy men, aged 38 and 39 years, with meningitis due to group B streptococci are described. These patients are unique as only one or two adults with group B streptococcal meningitis without predisposing diseases have been reported previously.
The pharmacokinetics of dexamethasone alcohol is described in six male and six female healthy adult volunteers who each received 8 mg of dexamethasone phosphate by bolus intravenous injection. Quantitation of the alcohol was done using a high-performance liquid chromatographic method with improved specificity. Statistical evaluation of the results generated by nonlinear least-squares regression analysis of the plasma concentration-time data shows that the phosphate ester is very rapidly hydrolyzed to the alcohol and a biexponential equation is the simplest polyexponential equation that is consistent with the data. The terminal phase half-life t1/2 beta was significantly greater (P less than 0.05) in males (mean 201.5 min) than in females (mean 142.3 min). They prolonged t1/2 beta in males did not appear to be caused by an impaired capacity to eliminate dexamethasone since the total plasma clearance did not differ between males (mean 24.5 ml/min) and females (mean 242.9 ml/min). There was, however, a high positive correlation between t1/2 beta and Vdss among the 12 adults (r = 0.92, p less than 0.001). There were also significant correlation between Vdss and body weight (r = 0.67, p less than 0.05) and t1/2 beta and body weight (r = 0.80, p less than 0.01). The difference in body weight between the sexes seems to be the main factor contributing to the difference observed in t1/2 beta. An average of only 2.6% of the dose was found unchanged in a 24-hr urine sample, and hence it appears that dexamethasone is primarily eliminated by extrarenal, probably hepatic, mechanisms.
The clinical symptoms of floride Cytomegalovirus infections of 18 previously healthy adults are reported. Fever was generally observed. In most cases myocarditis or hepatitis could be identified. Two of our patients died of on severe myocarditis. In 3 patients Guillain-Barré-syndrome was observed. Only in few of our cases the clinical picture was characterized by mononucleosis with systemic swelling of lymphonodes and thrombocytopenia or by pneumonia. Other symptoms were found quite seldom. The diagnosis of cytomegalovirus infection could be ascertained by: 1. detection of cytomegalovirus IgM antibody titers of greater 1:64, 2. a four fold increase in the titer of complement fixing antibodies, 3. Virus isolation from urine.
Background: Subjective cognitive complaints (SCCs) are common in middle-aged and older adults and may reflect early cognitive changes, alongside alterations in stress, mood, sleep, and quality of life. N-PEP-12 is a peptide-based nutritional supplement with potential neuroprotective effects, but evidence of its benefits in healthy adults with SCCs remains limited. Objective: To evaluate the effects of N-PEP-12 supplementation on attention, cognitive function, and mental wellbeing in healthy middle-aged and older adults with SCCs. Methods: In this prospective, randomized, double-blind, placebo-controlled trial, 276 participants aged 50-75 years with SCCs and no clinically significant cognitive impairment were randomized to placebo, N-PEP-12 45 mg, or N-PEP-12 90 mg. Assessments were performed at baseline and after 30, 90, and 180 days. Primary outcomes included Test of Attentional Performance measures. Secondary outcomes included WAIS-IV Digit Span Forward and Backward, perceived stress, mood, sleep quality, and EQ-5D-5L visual analog scale. Results: Across the three primary attention outcomes analyzed jointly in a multivariate repeated-measures model, there was a significant group-by-visit interaction (p = 0.003) and a significant effect of visit (p < 0.001), without a significant main effect of treatment arm (p = 0.133), indicating a time-dependent treatment effect. This result was obtained in a sensitivity analysis population in which missing values were imputed under assumptions least favorable to the active arms. In exploratory endpoint-specific comparisons at 90 days, both N-PEP-12 groups showed greater improvements than placebo in alertness, attention omissions and memory omissions, and Digit Span Forward and Backward scores also improved. In a subsequent uncontrolled extension phase, in which all participants received active treatment, participants initially assigned to placebo showed comparable improvements after switching to N-PEP-12 90 mg. These observations are exploratory. Adverse events were infrequent and similarly distributed across groups. Conclusions: N-PEP-12 supplementation was associated with improvements in attention, working memory, and mental wellbeing in healthy middle-aged and older adults with subjective cognitive complaints. These findings support further investigation of N-PEP-12 as a nutritional intervention for early subjective cognitive changes associated with aging.
We studied the metabolic kinetics after short-time infusion of a 10% standardised L-amino-acid-mixture in 19 healthy adults. The following results were of special interest: 1. Nearly all amino-acids had half life times between 7 and 10 minutes. 2. The male adults showed averagely higher clearance and transfer rates in contrast to female. There was a statistical difference for serine and alanine in the transfer rates, for serine, methionine and glycine in the clearance. 3. The maximum of daily turnover could be calculated for about 5,6 g/kg body weight. Based on the measured transfer rates we discuss the composition of some standardised L-amino-acid-mixtures.
Ingestion of E. coli O83 bacteria preceded by intake of 2 g of NaHCO3 resulted in the bacteria appearing as a transient strain in the stool in 6 out of 11 healthy adult individuals. No rise in serum, urine or parotid fluid antibody levels against the crude O antigen from E. coli O83 bacteria could be detected using the enzyme-linked immunosorbent assay (ELISA) or the indirect haemagglutination (IHA) technique. In contrast, a serum antibody response was registered in four individuals with the ammonium sulphate precipitation (ASP) technique. The rise in antibody level was accompanied by an increase in relative average antibody avidity. Significantly lower levels of serum antibodies against the E. coli O83 and O6 antigens were recorded using the ASP technique as compared to those for O2, O4 and O75 antigens.
A cytomegalovirus (CMV) induced lymphocyte tranformation test (LTT) performed as a microtechnique assay is described. Investigations were done in a group of twenty-five healthy adults with normal lymphocyte reactivity to phytohaemagglutinin and previously encountered antigens. Lymphocyte reactivity was established in CMV-seropositive persons using heat-inactivated cell-free CMV strain AD 169 in an optimal stimulating dose of 10(1-5) TCID 50. Positive CMV-LTT results were shown to be induced by purified inactivated CMV. Most persons (twelve out of seventeen) with antibodies against CMV-induced late or virus-structure antigens (LA) showed positive (stimulation index greater than 2-0) CMV-LTT results. Magnitude of CMV-LTT responses was positively related to the CMV-LA Ab titres (P less than 0-01). All persons (six) with antibodies against CMV early or non-structural antigens showed positive CMV-LTT results and highest stimulation rates were found in this group. Generally CMV-seronegative persons were non-responsive. Only in one case (LA Ab titre 10) a borderline positive response (stimulation index 2-3) was seen. The CMV-LTT was shown to have virus-specific properties because it was not related to simultaneously performed LTTs with Epstein-Barr virus and Herpes simplex virus in the same persons. It is concluded that CMV-LTTs are useful virus-specific in vitro techniques for the study of CMV-directed lymphocyte reactivity. Its possible relationship to other cell-mediated immunity tests and its practical applications are discussed.
PURPOSE: Gefurulimab, a novel dual-binding nanobody targeting complement component 5 (C5), is in clinical development for anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. Gefurulimab has a low molecular weight, enabling subcutaneous (SC) self-administration by autoinjector (AI) or prefilled syringe with needle safety device (PFS-SD). We compared gefurulimab pharmacokinetic (PK) exposure and safety in healthy adults following a single SC dose administered by AI versus PFS-SD. METHODS: In this phase 1, open-label, randomized, parallel-group study (NCT06208488), healthy participants aged 18 to 65 years were stratified by weight and randomized equally to 1 of 6 combination groups of device and injection site (abdomen/thigh/upper arm). Participants received a single SC dose of gefurulimab on day 1 and were assessed throughout the 92-day evaluation period. Primary endpoints were PK parameters for each device: maximum observed concentration (Cmax) and area under the serum concentration-time curve (AUCinf, AUClast). PK across injection sites, pharmacodynamics, safety, immunogenicity, and device performance were also assessed. FINDINGS: Overall, 175 participants were randomized: AI (n = 87), PFS-SD (n = 88). Geometric least squares mean ratios (90% CI) comparing AI/PFS-SD for Cmax, AUCinf, and AUClast were 97.6% (94.5-100.8), 99.6% (96.1-103.3), and 98.8% (95.2‒102.6), respectively. Secondary analyses found no meaningful differences in PK parameters across injection sites. Serum-free C5 concentrations over time, treatment-emergent adverse event (TEAE) profiles, and antidrug antibody responses were similar between cohorts. Most TEAEs were mild; none led to study discontinuation. IMPLICATIONS: SC administration of gefurulimab by AI and PFS-SD was well tolerated with comparable exposure, meeting bioequivalence criteria.
Analysis of the literature data on the significance of normal intestinal microbial population in the vital activity of the organism, and also on the sequelae of unfavourable shifts in the intestinal microecology is presented. The results of personal studies on the composition of normal microbial population in healthy adults are discussed; criteria for the assessment of normal intestinal biocenosis are given. The importance of bifidum flora is emphasized, and the necessity of its correction in various pathological conditions is underlined.
The synthesis of very high specific activity 25-OH-vitamin D3 (78 Ci/mmol) has made possible the study of the metabolism and plasma disappearance of 3H after a single dose of 3H-1,25-(OH)2-D3 in quantities that are only 10-20% of the endogenous plasma pool. We studied seven healthy adults who were given doses of 1,25-(OH)2-D3 ranging from 30-2300 pmol. Plasma disappearance was rapid with only 14 +/- 2% of administered 3H remaining in the plasma pool 4 h after labeling. Plasma metabolite profiles during the first 4 h showed only 1,25-(OH)2-D3. Thereafter, significant amounts of other metabolites were detected. The 6-day cumulative excretion of 3H in urine and feces (virtually all associated with metabolites of 1,25-(OH)2-D3) averaged 16 +/- 3% and 49 +/- 11% of the dose, respectively. Compartmental analysis of the isotope data for two subjects who received the smallest doses of 1,25-(OH)2-D3 indicated that endogenous renal 1,25-(OH)2-D3 synthesis rates approximate 0.8-2.4 nmol/day (0.3-1.0 microgram/day).