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PubMed1977

Reaction time variability in epileptic and brain-damaged patients.

Median reaction times and intra-individual variability were studied in epileptic (N = 63), brain-damaged (non-epileptic) (N = 25) and control patients (N = 25) using a six and one half minute visual, continuous reaction time task. Epileptic and brain-damaged groups were significantly slower than control patients on median reaction times at the 10th, 50th, and 90th percentiles and on the differences between the 10th and 90th percentiles. Thus both general slowing and greater intra-individual variability were found in the epileptic and brain-damaged patients. Reaction times were not related to presence, type and severity of EEG abnormality or to age of onset of epilepsy. Grand mal patients did have significantly greater variability than other types of seizure patients. Epileptic and brain-damaged patients did not differ significantly on any reaction time variables. Both groups were discriminated significantly from the controls on all reaction time measures, especially on the intra-individual variability measure.

Adolescent↗
PubMed2026

Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD): A collaborative platform for behavioral analysis across the lifespan.

Understanding cognitive aging requires approaches that capture individual variability while enabling integration across studies. In rodent models, behavioral data are central to this effort, yet cross-laboratory differences in experimental design limit comparability and constrain secondary analysis. To address this gap, we developed the Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD), a first-of-its-kind collaborative repository aggregating trial-level Morris water maze data from multiple laboratories. ID-CARD is designed to support large-scale, integrative analyses and to facilitate secondary use of existing behavioral data in alignment with emerging data-sharing and transparency initiatives. Rather than imposing retrospective harmonization of experimental protocols, we implemented a normalization and modeling framework that enables comparison of learning trajectories while preserving meaningful variation across studies. Behavioral data from > 5000 rats spanning common strains, both sexes, and multiple ages were normalized in training and performance domains and fit with a logarithmic function to derive an error accumulation rate coefficient (EARC) as a measure of spatial learning. Age was strongly associated with increased EARC, indicating attenuated learning, even after adjusting for non-spatial cue performance. Analyses of goodness of fit revealed systematic structure in learning dynamics, where age was associated with reduced learning-curve conformity after accounting for overall performance. Inter-individual variability in spatial learning also increased with age, with strain-specific interactions. These findings demonstrate that integrated analysis of heterogeneous behavioral datasets can yield robust, individual-level insights into cognitive aging. ID-CARD provides a scalable resource and analytic framework to advance discovery in behavioral neuroscience by enabling reuse, integration, and comparative analysis of existing data.

Cognitive aging↗
PubMed2025

Development and Validation of a Novel LC-MS/MS Based Proteomics Method for Quantitation of Retinol Binding Protein 4 (RBP4) and Transthyretin (TTR).

Retinol binding protein 4 (RBP4), the circulating carrier of retinol, complexes with transthyretin (TTR) and is a potential biomarker of cardiometabolic disease. However, RBP4 quantitation relies on immunoassays and western blots without retinol and TTR measurement. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous absolute quantitation of circulating RBP4 and TTR is critical to establishing their biomarker potential. Surrogate peptides with reproducible, linear LC-MS/MS response were selected. Purified proteins were used as quantitation standards and heavy-labelled peptides as internal standards. Matrix effects were evaluated. The validated method was applied to measure inter- and intra-individual variability in RBP4 and TTR concentrations in healthy individuals and patients with diabetic kidney disease. Quantitation was linear for the clinically relevant concentration ranges of RBP4 (0.5-6 &#x3bc;M) and TTR (5.8-69 &#x3bc;M). Assay inter-day variability was <12% and precision within 5%. The inter-individual variability for RBP4 and TTR concentrations was 18-26%, while intra-individual variability was similar to assay variability. RBP4 and TTR quantitation correlated with commercially available ELISA assays. The developed LC-MS/MS method enables simultaneous absolute quantitation of RBP4 and TTR in serum and plasma that can be applied to clinical biomarker studies and stoichiometric measurements of circulating RBP4, TTR, and retinol.

Retinol binding protein 4 (RBP4)↗
PubMed1976

[Investigations on the Variability of the phasic pupillary light reflex (author's transl)].

Infrared pupillography was used to determine physiological time parameters of the direct phasic light reflex in 101 normal subjects. These parameters include latency, contraction and redilatation times as well as total reaction time, measured in response to 4 different light stimulus intensities. A total of more than 4000 pupillary stimulations in these subjects was analyzed statistically. The study of these time parameters included determination of the mean, the standard deviation and three dimensional analysis of variance, with the following results: 1. The physiological time parameters are bilaterally symmetrical. 2. The most stable parameters with least variability in an individual subject were latency and contraction time. The redilatation time, however, showed marked intra-individual variability. 3. Variance analysis revealed a high degree of correlation among the different parameters to light stimuli of varying intensity. 4. There was a highly significant prolongation of latency and of contraction time with increasing age. 5. No sex dependent effect on physiological time parameters was found. In addition, no interaction among light stimulus intensity, age and sex could be detected. Possible applications of the method for clinical neurological examination are discussed.

Adolescent↗
PubMed1979

Physiological aspects of the effects of sound on man and animals.

A review of some short-term and long-term physiological effects of sound on non-auditory body functions is given. It is pointed out that the short-term effects depend closely on the acoustic properties of the sound. Habituation is rapid for steady signals but slow for interrupted ones. Irrelevant, meaningless sound, presented to rats over their life-time in such a way as to simulate an industrial acoustic environment, did not affect blood pressure, life-span or morbidity incidence. As far as the injurious effect of sound on the inner ear is concerned, it was shown that spontaneously hypertensive rats were considerably more susceptible to such impairment than were normotensive ones. Hence sound does not produce hypertension, but susceptibility to ear injury may be greater in hypertensive individuals. The protential role which individual variability in physiological properties of the sound conduction system might play for the observed individual variability in noise-induced hearing loss is also discussed.

Animals↗
PubMed1976

The TSH response to thyrotropin-releasing hormone (TRH) in young adult men: intra-individual variation and relation to basal serum TSH and thyroid hormones.

The response of serum TSH to duplicate tests with each of two doses of TRH (30 mug and 500 mug) was studied in 22 normal young adult men. The mean intra-individual variability of the response assessed by duplicate testing (coefficient of variation) was 17% but was as high as 63% in individual subjects. While the actual range of peak TSH values after 500 mug TRH was 2.7-19.5 muU/ml, those subjects (3 of 22) with a peak TSH value between 2 and 5 muU/ml on one occasion were all greater than 5 muU/ml on another. Thus, despite the intra-individual variability, a peak TSH value after 500 mug TRH of less than 2 muU/ml indicates TSH deficiency and greater than 5 muU/ml indicates normal TSH reserve. A peak value of 2-5 muU/ml is an indication for retesting;; a peak TSH value greater than 5 muU/ml on retesting indicates normal TSH reserve. The use of the maximal increase in TSH above basal values (max deltaTSH) did not have a clear advantage over the use of the peak TSH value although a max deltaTSH greater than 4 muU/ml was equivalent to a peak value greater than 5 muU/ml. No information was lost by using only the TSH value at 30 min after TRH instead of multiple samples. In using these values differences in assay technique should be considered; for example, the use of human TSH standard MRC 68/38 instead of human TSH standard A (MRC 63/14) causes a fall of about 1/3 in measured serum values. The overall TSH response to 500 mug TRH was statistically greater than the response to 30 mug TRH (P less than 0.01); however, in 10 of 22 subjects the response to the two doses was about the same, suggesting that the dose response of TSH to TRH, between 30 mug and 500 mug TRH, is quite shallow. The TSH value 60 min after 500 mug TRH was within 2 muU/ml of the peak TSH value in 12 of 22 subjects on at least one occasion; this pattern of a delayed fall is a normal variant. The peak TSH response to TRH correlated well with the basal level of TSH (P less than 0.001) and thus can be considered a magnifier of the basal level of TSH in normal subjects. While the peak TSH value did not correlate with the basal level of T3, there was a moderate negative correlation of the peak TSH value with the basal level of T4 (P less than 0.02), suggesting that the concentration of serum T4 within the normal range is a determinant of TSH secretion.

Adolescent↗
PubMed1976

Effects of transcendental meditation on fine motor skill.

46 college female volunteers were given 66 10-sec. trials on the pursuit rotor task in 3 practice sessions (18, 30, and 18 trials/sessions). After the first 18 trials, the 23 subjects who were practiced Transcendental Meditators mediated for a 20-min. period followed by a 5-min. "waking" phase prior to the performance of a further 30 trials on the rotor. A 4-min. rest was taken before resuming practice for the final 18 trials. The other 23 subjects, who were not meditators, followed the same procedures except instead of mediating they sat quietly with closed eyes. In terms of performance, learning, reminiscence and intra-individual variability, the two groups were similar. These results were not in accordance with the expectations that these parameters would reflect the facilitative effects of Transcendental Meditation on alertness, awareness, consistency, and resistance to stress. After the meditation session, inter-individual variability was increased for the mediation group. While the conclusion that the practice of Transcendental Meditation does not benefit acquisition of fine perceptual-motor skill appears strong, further investigation would assist in obtaining a more complete understanding of such effects on perceptual-motor behavior.

Female↗
PubMed1979

Respiration in conscious dogs at rest and during exercise.

25 mongrel dogs (average b.w. 24.6 kg) were studied on several occasions at rest and during treadmill exercise of up to 10 mph (15% incline). Minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), tidal volume (VT) and respiratory frequency (f) were determined at rest and at each level of exercise. Individual variability in resting VO2 was considerable (71--695 ml/min). Most often the dogs panted, with VE's above 25 liters/min and f's above 100 min-1. The averate VE/VO2 was 109 at rest. VO2 was linearly related to VE (VO2 = 9.17 VE + 66.9; r = 0.80). Differences in resting VE were largely due to differences in f (f = 3.57 VE + 21.2; r = 0.82). Considerable individual variability in VO2 for a given work load was also observed during exercise. Some dogs showed significant differences in VO2 from experiment to experiment while running at a given treadmill speed. These differences were largely related to the levels of VE. VE/VO2 decreased to 50. We found a leveling off of VO2 (at about 60 ml/min/kg) at treadmill speeds of 5 mph, suggesting that the maximal VO2 in dogs is less than previously reported.

Animals↗
PubMed2025

Structural diversity and evolutionary constraints of oxidative phosphorylation.

The oxidative phosphorylation (OxPhos) system is central to metabolism. The more than 90 structural subunits are encoded by different chromosome categories (autosomal, X, and mtDNA). The system is envisioned as an invariant structure between cells and individuals. However, a comprehensive analysis of the 1,000 Genomes Project data reveals unexpected genetic intra-individual variability resulting from the heterozygosity of diploid autosomal genes, while diversity at the population level is generated by variability in mtDNA. We characterized the different levels of structural constriction at evolutionary and population levels for all OxPhos protein residues. To support this analysis, we developed ConScore, a conservation-based predictor of variant impact within OxPhos proteins (area under the receiver operating characteristic curve [ROC-AUC] = 0.97; area under the precision-recall curve [PR-AUC] = 0.94). Notably, for the nuclear-encoded subunits, we found mechanisms limiting individual variability as allelic imbalance or homozygosity bias. Integrating structural, functional, and genetic data, we highlight the significance of each OxPhos protein position, expanding insights into its role in speciation and disease.

Oxidative Phosphorylation↗
PubMed2024

Exclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn's disease.

Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn's disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with Lachnospiraceae and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free Il10-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.

Crohn Disease↗
PubMed2026

A prospective pharmacokinetic interaction study between rifampicin and fusidic acid for the treatment of staphylococcal infections.

OBJECTIVE: Fusidic acid with rifampicin is used for the treatment of severe staphylococcal infection, particularly prosthetic joint infections. Previous studies using twice daily fusidic acid showed rifampicin increases fusidic acid clearance, potentially causing sub-therapeutic concentrations. It is uncertain whether this occurs with three-times daily dosing. This study sought to re-evaluate this potential drug-drug interaction. METHODS: In this prospective, open-label drug-drug interaction population pharmacokinetic (PK) study, participants were randomized to receive fusidic acid or rifampicin for 24&#x2005;hours, followed by combination therapy for the duration of treatment. Drug concentration assays used liquid-chromatography mass spectroscopy on dried blood spots. Population PK models were built for fusidic acid, rifampicin and 25-desacetyl rifampicin. RESULTS: Ten participants were recruited. Inter-individual variability for both absorption (98.1%) and clearance (77.8%) were high for fusidic acid. A population pharmacokinetic model for fusidic acid revealed that early autoinhibition dominated over later rifampicin-mediated induction, resulting in a net decrease in fusidic acid clearance. The mean fusidic acid area under the curve during each dosing interval (AUC&#x3c4;) at steady state was 1.76-fold [0.049, 34.918] higher relative to Day 1, despite high uncertainty.Large inter-individual (110%) variability in absorption was observed for rifampicin. There was no apparent effect on rifampicin metabolism by fusidic acid co-administration, however, fusidic acid decreased clearance of 25-desacetyl rifampicin. CONCLUSION: In patients treated with fusidic acid three times daily in combination with rifampicin, autoinhibition potentially counteracted rifampicin induction such that fusidic acid concentrations were not reduced. Rifampicin clearance was not affected by fusidic acid, but 25-desacetyl rifampicin clearance was decreased. There was large inter-individual variability in the observed concentrations and final parameter estimates.

Fusidic Acid↗
PubMed1976

[Individual anatomic variability of Forel's field H].

The investigation was performed in serial frontal sections of 100 preparations of the diencephalon and midbrain made 1 mm from one another. The shape of Forel H field was found to be very variable, changing from the rectangular to triangular shape in pararubralparts, and from oval to semioval-in prerubral parts. The size and position of Forel H field proved to change in relation to intracerebral reference points: posterior comissure, medial and intercomissural planes used in stereotaxical technique.

Adult↗
PubMed1979

Efficacy of cognitive/noncognitive measures in predicting resident-physician performance.

There has been relatively little research on the relationship between the clinical performance of physicians and the criteria used by medical school admissions and promotions committees. The studies which have been done primarily relate clinical performance to cognitive criteria. They have usually found only negligible relationships. By considering both cognitive and noncognitive variables, several investigators recently have improved the prediction of clinical performance in medical school. The present authors attempt to determine the increase in predictive efficiency attained by adding noncognitive variables to cognitive variables in predicting clinical performance of residents. The results of this investigation indicate that a combination of cognitive and noncognitive predictor variables functions much better than any individual variable or even any specific class of variables in predicting the postgraduate clinical performance of physicians.

Clinical Competence↗
PubMed2025

Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson's disease.

Human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic cells (mDACs) represent a promising source for autologous cell therapy in Parkinson's disease (PD), but standardized regulatory criteria are essential for clinical translation. In this pre-clinical study, we generated multiple clinical-grade hiPSC lines from freshly biopsied fibroblasts of four sporadic PD patients using episomal reprogramming and differentiated them into mDACs using a refined 21-day protocol. Rigorous evaluations included whole-genome/exome sequencing, RNA sequencing, and in&#xa0;vivo studies, including a 39-week Good Laboratory Practice-compliant mouse safety study. While mDACs from all lines met safety criteria, mDACs from one patient failed to improve rodent behavioral outcomes, underscoring inter-individual variability. Importantly, in&#xa0;vitro assessments did not reliably predict in&#xa0;vivo efficacy, identifying dopaminergic fiber density as a key efficacy criterion. These findings support comprehensive quality control guidelines for autologous cell therapy and pave the way for a clinical trial with eight sporadic PD patients, scheduled to commence in 2025.

Humans↗
PubMed1978

Relationships among measures of preferred tempo and motor rhythm.

Male and female subjects (Ns = 100) performed an accuracy task involving consecutive arm swings at a self-paced tempo. Following this, the subjects performed a motor rhythm task keeping in cadence with audio-visual stimuli presented at their preferred tempo. Previous findings regarding the magnitude of individual differences in preferred tempo and within-individual variability were replicated, as was the absence of sex differences for these attributes. With regard to motor rhythm, the findings indicated that (a) constant and variable error, and not absolute error, were the appropriate measures of performance, (b) there were no sex differences either in spatial or temporal accuracy or in trial-to-trial consistency of performance, (c) substantial individual differences were present in rhythmic accuracy, as were moderate individual differences in variability, (d) neither rhythmic accuracy nor variability was appreciably related to preferred tempo, and (e) spatial and temporal accuracy are relatively independent components of rhythmic accuracy.

Acoustic Stimulation↗
PubMed1979

Quantitative analysis of mating behavior in aging male Drosophila melanogaster.

Dynamic changes in quantitative aspects of mating behavior of the male fruit fly as its life unfolds, from eclosion through maturity (peak performance) and "physiological death" (loss of fertility followed by complete loss of ability to mate), towards actual death, have been identified in this work by observations and measurements on 28 male fruit flies of the Oregon R strain studied individually. At weekly sessions from the first day of their imaginal life until their natural death, each fly was given the opportunity to mate with up to three virgin females during a one-hour period. Length of the latency period of each accomplished mating and duration of copulation were recorded. After mating the females were allowed to lay eggs for 24 hours and the number of offspring was counted 26 days later. The period between 1 and 4 weeks of age is characterized by peak and fairly constant performance: multiple matings, short latencies, long durations of copulation, and high degree of fertility (number of offspring); then a decline sets in, in some measures slower than in others, as the flies age. Large intra- and inter-individual variabilities were, however, found which obscure possible correlations between individual measures of mating ability and length of life. At the individual level, a preliminary analysis showed a good correlation (r = 0.80 and 0.79) between life span and week of last mating (onset of impotence) or week of last fertile mating (onset of sterility). At the population level it was found that a number of measures, i.e. number of remaining maters at each age, number of remaining fertile maters and total number of matings, had an age-course similar to survivorship but anticipated it by 4--6 weeks. Other measures, such as number of multiple matings and number of offspring declined with age faster than survivorship.

Aging↗