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Some relations between dissolution rates and physical parameters of a drug in aqueous micellar solutions of a non-ionic surfactant.

Dissolution rates of salicylic acid from a constant surface area into a series of aqueous micellar polysorbate 20 solutions at pH 1-0 to 4-0 have been measured using two different methods; a stirred beaker and a rotating disc technique. The micellar molecular weight of polysorbate 20 has been obtained from light scattering and differential refractometry data and used with other independently determined physical data to calculate diffusion coefficients of the diffusing species. Linear multiple regression analysis was used to assess the dependence of drug dissolution rate on the diffusion coefficient and the viscosity of the dissolution medium.

Colloids

Factors affecting the binding of tricyclic tranquillizers and antidepressants to human serum albumin.

The linear free energy-related model for structure activity relations developed by Hansch & Fujita (1964) has been used to correlate the binding of tricylic tranquillizers and antidepressants to human serum albumin (HSA) with hydrophobic and electronic parameters. The parameters chosen being the chromatographic parameter (Rm) and the affinity of charge transfer complex formation (kc). The relative importance of these factors has been assessed by linear and multiple linear regression analysis. Results show that the major factor in binding is electronic with only a minor contribution from the hydrophobic parameter.

Antidepressive Agents, Tricyclic

Subcellular distribution of nucleotide cyclases in rat intestinal epithelium.

The subcellular distributions of adenylate cyclase and guanylate cyclase were determined for the mature enterocyte from the rat duodenum. Brush-border and basolateral membranes were prepared from isolated cells by an analytical isolation procedure, and multiple linear regression analysis was used to obtain a quantitative estimate of the distribution of recovered cyclase activities between the brush borders and basolateral membranes. Adenylate cyclase was largely confined to the basolateral surface of the epithelium, whereas guanylate cyclase was found on the brush-border and basolateral membrane fractions in the ratio 2.4:1. There was no evidence for the presence of nucleotide cyclases in the cytosol. Guanylate cyclase in both the brush-border and basolateral membranes was stimulated by epinephrine, insulin, and Triton X-100, but not by carbachol. Adenylate cyclase was not influenced by epinephrine, but was markedly stimulated by NaF and vasoactive intestinal peptide. These results are discussed in relation to the effects of hormones on transport across the small intestine.

Adenylyl Cyclases

Low-Dose Radiation-Induced Expression of Exosomal miRNAs in the Serum of Medical Radiation Workers.

Objective: Long-term low-dose ionizing radiation may alter genomes and cause diseases. This study examined serum exosomal miRNA differences among radiation-exposed medical workers by work types. Methods: High-throughput sequencing screened serum exosomal miRNAs in diagnostic radiologists, interventional radiologists, and nuclear medicine doctors. qRT-PCR validated differentially expressed miRNAs. Results: 410 differentially expressed miRNAs, including 102 downregulated and 308 upregulated miRNAs, enriched in 15 KEGG pathways. Four miRNAs were validated. miR-30e-5p, miR-155-5p and miR-486-5p differed significantly among groups(P<0.01).The expression levels of these three miRNAs were lower in the nuclear medicine group than in the diagnostic group (0.25&#xb1;0.05vs3.89&#xb1;8.62,0.10&#xb1;0.15vs7.03&#xb1;15.75,0.37&#xb1;0.39vs4.46&#xb1;9.64;Z=3.542,3.335,9.859;P<0.01), whereas miR-155-5p was lower in the interventional group than in the diagnostic group(1.32&#xb1;2.43vs 7.03&#xb1;15.75;H=11.889,P=0.003), miR-486-5p was higher(9.54&#xb1;19.39vs4.46&#xb1;9.64; H=9.859,P=0.007). All four miRNAs showed higher expression in the 14-31-year work-experience group, and all four also showed age-dependent differences, with miR-30d-5p and miR-486-5p showing the age-related differences (P<0.01). Combined detection of the four miRNAs improved discrimination among occupational categories (AUC=0.784). Multiple linear regression analysis showed that sex was associated with all four miRNAs, whereas work type was associated with miR-30d-5p and miR-155-5p (P<0.05). Conclusion: Serum exosomal miR-30e-5p, miR-155-5p, and miR-486-5p are promising biomarkers for monitoring radiation-induced damage, supporting occupational protection and health management.

exosomes

Identification of intragenic variants in pediatric patients with intellectual disability in Peru.

BACKGROUND: Intellectual disability in Latin America can reach a frequency of 12% of the population, these may include nutritional deficiencies, exposure to toxic or infectious agents, and the lack of universal neonatal screening programs. In 90% of patients with intellectual disability, the etiology can be attributed to variants in the genome. OBJECTIVE: to determine intragenic variants in patients with intellectual disability between 5 and 18 years old at Instituto Nacional de Salud del Ni&#xf1;o. METHODS: It is a descriptive cross-sectional study with convenience sampling. A total of 124 children diagnosed with intellectual disability were selected based on psychological test results and availability for whole exome sequencing. In addition, a chromosomal analysis of 6.55&#xa0;M was performed on ten patients with a negative result in sequencing. Relative and absolute frequencies and measures of central tendency and dispersion were determined according to their nature. In addition, multiple linear regression and Poisson regression were used to determine the association between some clinical characteristics and the probability of occurrence in patients with positive results. RESULTS: The median age of the patients was 6.3 (IQR&#x2009;=&#x2009;5.95), males accounted for 57.3%, and 91.9% of the cases had mild intellectual disability. Exome sequencing determined the etiology in 30.6% of patients with intellectual disability, of which 52.6% were autosomal dominant inheritance. The most frequent genes found were MECP2, STXBP1 and LAMA2. A broad genotype-phenotype correlation was identified, highlighting the genetic heterogeneity of intellectual disability in this population. The presence of dermatologic lesions, dystonia, peripheral neurological disorders, and fourth finger flexion limitation were observed more frequently in patients with intellectual disability with "positive results". CONCLUSIONS: This study shows that one-third of patients with intellectual disability exhibit intragenic variants, highlighting the importance of genetic analysis for accurate diagnosis. The identification of genes such as MECP2, STXBP1, and LAMA2 underscores the genetic heterogeneity of intellectual disability in the studied population. These findings emphasize the need for genetic testing in clinical management and the implementation of early detection programs in Peru.

Humans

The Impact of Chatbot Type and Normative Messaging on Chatbot Usage Intention Based on the Health Technology Acceptance Model: Randomized Controlled Trial.

BACKGROUND: Digital health tools, such as health chatbots, may improve access to scalable health support, but adoption remains inconsistent. Existing models do not fully integrate technology acceptance factors with health motivation factors relevant to digital health use. OBJECTIVE: This study proposed and tested the health technology acceptance model and examined whether normative message framing and chatbot type were associated with health motivation, technology acceptance, and intention to use a health chatbot. METHODS: In October 2025, we conducted a 4 &#xd7; 2 between-participants online experiment with 1000 US adults recruited from a nationally representative YouGov panel. Participants were randomized to 1 of 8 conditions varying norm message type (self-oriented, peer-oriented, expert-oriented, or family-oriented) and chatbot type (AI-powered or rule-based) in a cancer prevention and genetic risk information scenario. Outcomes included descriptive norms, injunctive norms, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, perceived ease of use, trust, privacy concerns, and usage intention. Data were analyzed using a multivariate ANOVA with Bonferroni-adjusted post hoc tests and multiple linear regression. RESULTS: Peer-oriented and family-oriented messages produced higher usage intention than expert-oriented messages, and peer-oriented messages also increased descriptive norms, injunctive norms, self-efficacy, and trust. AI-powered chatbots were associated with higher usage intention (P=.02) and greater trust (P=.008) than rule-based chatbots. In regression analyses, the model explained 50.8% of the variance in usage intention. Usage intention was positively associated with descriptive norms (&#x3b2;=0.087; P=.003), injunctive norms (&#x3b2;=0.078; P=.009), perceived susceptibility (&#x3b2;=0.051; P=.03), perceived benefits (&#x3b2;=0.253; P<.001), and trust (&#x3b2;=0.33; P<.001), and negatively associated with perceived severity (&#x3b2;=-0.047; P=.049) and privacy concerns (&#x3b2;=-0.11; P<.001). Perceived ease of use and self-efficacy were not significant predictors. CONCLUSIONS: The health technology acceptance model was a useful framework for explaining the intention to use a health chatbot by combining technology acceptance and health motivation constructs. Both social design features and chatbot design features shaped adoption-related beliefs, with peer-oriented and family-oriented framing and AI-powered chatbots showing particular promise. Trust and privacy concerns remained central determinants of intended use.

Humans

Birth weight of children with Down's syndrome.

The difference in birth weight between children with Down's syndrome and their siblings was estimated to be in the interval from .18 to .37 kg with 90 percent confidence, the Down's syndrome infants having the smaller mean birth weights. When we adjusted their birth weight, using a multiple linear regression analysis, to take into account several factors known to affect it, the difference in birth weight was only slightly less than the unadjusted difference. The data support the hypothesis that an extra chromosome No. 21 results in a smaller than expected birth weight.

Birth Order

Prolonged sleep apnea and respiratory instability: a discriminative study.

This report is based on a study of 53 infants, 28 of whom had clinically observed prolonged apnea (greater than or equal to 20 seconds) during sleep whereas the remaining did not. In addition to the clinical observations, each infant was studied in a sleep laboratory during a complete nap, and a continuous recording was made of respiratory activity and rapid eye movements. Measurements were made of all apneic pauses (greater than or equal to 2 seconds) observed in the laboratory and the two groups of infants were compared in terms of the frequency and average duration of apneic pauses, the longest apneic pause, the amount of periodic apnea, and the relative amount of apnea. The infants with prolonged sleep apnea had, during a single nap, more frequent and longer apneic pauses and more periodic apnea. This supports the hypothesis that respiratory instability during sleep and prolonged apnea have a common etiology. By employing a multiple linear regression model and including all laboratory apnea measures in a single analysis, a composite laboratory score was developed to differentiate members of the two groups. It would thus appear that the study of infants during a single nap could assist in the identification of infants at risk for prolonged sleep apnea and provide an indirect method for determining the influence of a number of variables on the occurrence of prolonged sleep apnea. Pediatrics, 59:962-970, 1977, SLEEP, APNEA, RESPIRATORY INSTABILITY.

Apnea

Interactions between anticonvulsants.

Anticonvulsant drug interactions have been investigated using multiple linear regression analyses. The one statistically significant interaction found was that in which phenytoin dosage decreased plasma carbamazepine concentrations. There was a suggestion that carbamazepine and phenobarb dosage tended to increase phenytoin levels. No interaction was detected between phenytoin and sulthiame. Studies in individuals suggested that ethosuximide may increase plasma phenytoin concentration and that clonazepam tends to decrease carbamazepine and phenytoin concentrations.

Anticonvulsants

Quantitative structure-activity relationships. V. A simple simple algorithm for Fujita-Ban and Free-Wilson analyses.

For quantitative structure-activity analyses a simple algorithm for the calculation of de novo group contributions by Fujita-Ban analysis is given. This algorithm corresponds in all details to a computer program for linear multiple regression analysis. However, the transformation of the original matrix to the normal equations matrix is easily achieved without a computer. The normal equations matrix can be solved with a modern desk calculator being equipped with a matrix ROM. Two examples are given to explain the algorithm; the calculation of all important statistical parameters is illustrated. As for quantitative structure-activity analyses this algorithm can be applied as well for the calculation of other additive parameters, such as pi from log P-values or omega from equilibrium constants.

Electronic Data Processing

Factors related to tardive dyskinesia.

The authors found a 31% incidence of tardive dyskinesia among 261 schizophrenic outpatients treated with neuroleptics. Multiple linear logistic regression analysis revealed a higher incidence of tardive dyskinesia among elderly patients, those with longer records of hospitalization, those for whom neuroleptic medication had little therapeutic effect, and those treated with fluphenazine. Patients manifesting tardive dyskinesia tended to have fewer parkinsonian symptoms than those without the disorder, especially when tremors and akathisia were excluded from consideration. Multiple linear regression analysis indicated that brain-damaged patients and male patients were more susceptible to severe forms of the disorder, even though these factors were not implicated in its initial appearance.

Adult

On the mechanism of assembly of the aspartate transcarbamoylase from Escherichia coli.

The mechanism of subunit assembly of aspartate transcarbamoylase from Escherichia coli was studied by following the kinetics of reassociation. The isolated trimetric catalytic subunit (c3) and dimeric regulatory subunit (r2) were mixed together and formation of the dodecameric native enzyme (c6r6) was monitored by measuring changes in activity. Under appropriate conditions the reassociation was second order with respect to the c3 concentration and the effects of varying r2 concentration on the second-order rate constant were examined. An optimum R2 concentration of about 0.07 micrometer was observed. A scheme of the assembly pathways is proposed and is based on the reversible formation of c3r2n (n = 0, 1, 2 or 3) as intermediates. Various combinations of two such c3r2n species are considered as possible rate-limiting steps. This model yields an expression which relates the experimentally determined (overall) second-order rate constant to the equilibrium constant (Kd) governing the formation of c3r2n, the r2 concentration, and four coefficients which reflect the contribution of different types of assembly processes. Using previously determined values of Kd, the above expression for each r2 concentration reduces to a linear equation with four unknowns. The experimental data were subjected to multiple linear-regression analysis and values for the four coefficients were found which gave an excellent fit. Our results show that reassociation of the subunits is a fast bimolecular reaction with rate constants in excess of 10(6) M-1 s-1. Our analysis also suggests that interactions involving a total of more than three r2 subunits (e.g. the combination of c3r2 with c3r6) might contribute significantly to the overall assembly. The influence of various ligands on the reassociation rate profile was also studied. All ligands examined were partially inhibitory to the formation of native enzyme. The effects of substrates were similar to those of CTP whereas the effects of ATP were substantially different. These observations can be readily interpreted by postulating different conformational changes induced by the ligands. These changes should alter the relative orientation of the subunit contacts which must be formed in the reassociation process. The interpretation is consistent with our previous model of the allosteric mechanism.

Aspartate Carbamoyltransferase

Patients' expectancies and improvement in treatment: the shape of the link.

It has been hypothesized (a) that patients' expectancies for therapeutic gain are linked to the clinical improvement that the patients realize in treatment; and (b) that patients' expectancies may play a causative role in such improvement. The first hypothesis has received empirical support, but the second has not. This study tested the causativeinterpretation of patients' expectancies and a second interpretation, which states that patients' expectancies predict, but do not cause clinical improvement. The shape of thelink between expectancy and improvement for hospitalized schizophrenics was explored. Based on motivation research it was reasoned that a curvilinear relationship between expectancy and improvement would support a causative interpretation and that a linear relationship would support a predictive interpretation of the nature of expectancy. Multiple regression analyses found a linear relationship between expectancies and objective measures of improvement for the patients, but no evidence of a curvilinear relationship between these measures. The results were interpreted as supporting a predictive interpretation of the expectancies of hospitalized schizophrenic patients.

Adolescent

An epigenome-wide study of selenium status and DNA methylation in the Strong Heart Study.

BACKGROUND: Selenium (Se) is an essential nutrient linked to adverse health endpoints at low and high levels. The mechanisms behind these relationships remain unclear and there is a need to further understand the epigenetic impacts of Se and their relationship to disease. We investigated the association between urinary Se levels and DNA methylation (DNAm) in the Strong Heart Study (SHS), a prospective study of cardiovascular disease (CVD) among American Indians adults. METHODS: Selenium concentrations were measured in urine (collected in 1989-1991) using inductively coupled plasma mass spectrometry among 1,357 participants free of CVD and diabetes. DNAm in whole blood was measured cross-sectionally using the Illumina MethylationEPIC BeadChip (850&#xa0;K) Array. We used epigenome-wide robust linear regressions and elastic net to identify differentially methylated cytosine-guanine dinucleotide (CpG) sites associated with urinary Se levels. RESULTS: The mean (standard deviation) urinary Se concentration was 51.8 (25.1) &#x3bc;g/g creatinine. Across 788,368 CpG sites, five differentially methylated positions (DMP) (hypermethylated: cg00163554, cg18212762, cg11270656, and hypomethylated: cg25194720, cg00886293) were significantly associated with Se in linear regressions after accounting for multiple comparisons (false discovery rate p-value: 0.10). The top hypermethylated DMP (cg00163554) was annotated to the Disco Interacting Protein 2 Homolog C (DIP2C) gene, which relates to transcription factor binding. Elastic net models selected 425 hypo- and hyper-methylated DMPs associated with urinary Se, including three sites (cg00163554 [DIP2C], cg18212762 [MAP4K2], cg11270656 [GPIHBP1]) identified in linear regressions. CONCLUSIONS: Urinary Se was associated with minimal changes in DNAm in adults from American Indian communities across the Southwest and the Great Plains in the United States, suggesting that other mechanisms may be driving health impacts. Future analyses should explore other mechanistic biomarkers in human populations, determine these relationships prospectively, and investigate the potential role of differentially methylated sites with disease endpoints.

Humans

Path analysis: application in an epidemiological study of echinococcosis in New Zealand.

The method of path analysis is described in detail. Application of this analyogical systems is demonstrated using data from an epidemiological study of echinococcosis in New Zealand. The results identified the major causal pathways determining Echinococcus granulosus prevalence in dogs, based on multiple regression analysis of a linear causal model constructed from prior biological and epidemiological knowledge. Only ethnic and sheep husbandry variables had important direct effect on prevalence in the North Island of New Zealand, with some climate factors (maximum temperature and relative humidity) and soil porosity acting indirectly through animal husbandry practices. It is suggested that path analysis, by permitting interaction between epidemiological theory and statistical analysis, provides a valuable additional tool to epidemiologists for the study of causal relationships among variables in multivariates systems.

Animals

Chromosome-scale genome assembly and genomic prediction of essential oil compounds in Atractylodes lancea for genomics-assisted breeding.

Atractylodes lancea rhizomes are used as crude drugs. Essential oil compounds, including atractylodin, hinesol, &#x3b2;-eudesmol, and atractylon, are key determinants of crude drug quality. Conventional breeding of A. lancea is difficult because of its perennial growth. In this study, a chromosome-scale reference genome of A. lancea (4.79 Gb) was generated, and genome-wide association studies (GWAS) and genomic predictions of essential oil compounds were conducted to explore the potential for genome-assisted breeding. Genotyping of 480 lines using double-digest restriction-site-associated DNA-sequencing yielded 29,136 high-quality SNPs. All the compounds showed high genomic heritability (h2 = 0.758-0.915), indicating strong genetic control. Despite the high genomic heritability, GWAS detected only one weak association with atractylon and no significant loci for the three compounds. However, genomic prediction achieved moderate to high accuracy across multiple models, particularly the ridge regression, genomic best linear unbiased prediction, and Bayesian approaches. The prediction accuracy, measured as the Pearson correlation coefficient between the observed and predicted values, exceeded 0.6 for all four essential oil compounds. These results demonstrate the efficacy of genomic selection for improving essential oil compound levels in A. lancea and provide a foundation for genome-assisted breeding of medicinal plants with long breeding cycles.

Atractylodes lancea

Comparison of summative assessments between simulated electronic health records versus traditional paper-based patient cases: A non-inferiority randomized controlled trial.

INTRODUCTION: Electronic health records are fundamental to contemporary pharmacy practice, yet evidence supporting their use in pharmacy education is lacking. This single-center, non-inferiority randomized controlled trial with blinded outcome assessment evaluated whether delivering patient cases via a simulated academic EHR (aEHR) was non-inferior to a traditional paper-based format in student exam performance. METHODS: 53 third-year PharmD students at the University of British Columbia were randomized 1:1 to complete a mock summative examination using either the aEHR or paper-based case delivery, stratified by self-reported EHR comfort level. The primary outcome was mean written exam score (%). Non-inferiority was pre-specified at a margin of 14%. Adjusted linear regression was used for the primary analysis, with a multiple imputation sensitivity analysis. Student perceptions were explored through post-exam focus groups analyzed using inductive thematic analysis. RESULTS: 42 students (21 per group) completed the exam and were included in the primary analysis. Mean scores were 66% (SD 11) in the aEHR group and 68% (SD 10) in the paper group. The adjusted mean difference (paper minus aEHR) was -2.2% (95% CI -9.2% to +4.8%), satisfying non-inferiority but not superiority. Sensitivity analysis (n&#xa0;=&#xa0;53) yielded consistent results (-2.3%; 95% CI -7.1% to +4.1%). Focus groups revealed initial student anxiety with the aEHR but recognized its alignment with clinical practice. DISCUSSION: These findings support the feasibility of integrating simulated EHRs into summative pharmacy assessments without compromising performance. CONCLUSION: Simulated EHRs are a non-inferior assessment medium compared with paper-based formats and represent a viable step toward technology-driven pharmacy practice environments.

Humans

The association between prenatal PM2.5 constituent exposure and gestational diabetes mellitus: Exploratory analysis of the potential modifying role of thyroid hormones.

The associations of PM2.5 constituents with blood glucose and GDM remain unclear, and the interplay between PM2.5 exposure and thyroid hormone levels in relation to GDM has not been well characterized. This retrospective cohort study included 1314 pregnant women with data collected through multiple methods. A generalized linear model analyzed PM2.5-glucose links, logistic regression assessed pollutant-GDM associations, and stratified analyses explored these relationships at different thyroid hormone levels. In the study population, first-trimester exposure to SO42- and BC correlated positively with FBG, as did PM2.5 and its components in the second trimester. First-trimester SO4&#xb2;&#x207b; exposure (OR=1.26, 95% CI: 1.06, 1.51) and second-trimester exposures to PM2.5 (OR=1.67, 95% CI: 1.19, 2.35), NO3&#x207b; (OR=1.34, 95% CI: 1.06, 1.68), and NH4&#x207a; (OR=1.33, 95% CI: 1.06, 1.65) were associated with increased GDM risk. Stratified analyses showed that second-trimester BC and OM were positively correlated with FBG in the high-TSH and low-FT4 strata, respectively. In addition, first-trimester exposure to SO42- (high TSH: OR = 1.42, 95% CI: 1.10, 1.84; low FT4: OR = 1.35, 95% CI: 1.05, 1.74) and to PM2.5 (high TSH: OR = 1.93, 95% CI: 1.14, 3.27; low FT4: OR = 1.82, 95% CI: 1.46, 2.25) in the second trimester were associated with higher odds of GDM. These findings show that PM2.5 exposure was associated with glucose dysregulation and GDM in pregnant women differently by trimester and component. Across the separate TSH- and FT4-stratified analyses, women in the high-TSH and low-FT4 strata, respectively, appeared to show greater susceptibility to air pollution-related GDM. These subgroup findings should therefore be interpreted as exploratory and require validation in future studies.

Effect modification