Variability In Time Course Research Articles

The human colon: Evidence for degenerative changes during aging and the physiological consequences.

The incidence of constipation increases among the elderly (>65 years), while abdominal pain decreases. Causes include changes in lifestyle (e.g., diet and reduced exercise), disease and medications affecting gastrointestinal functions. Degenerative changes may also occur within the colo-rectum. However, most evidence is from rodents, animals with relatively high rates of metabolism and accelerated aging, with considerable variation in time course. In humans, cellular and non-cellular changes in the aging intestine are poorly investigated. To examine all available studies which reported the effects of aging on cellular and tissue functions of human isolated colon, noting the region studied, sex and age of tissue donors and study size. The focus on human colon reflects the ability to access full-thickness tissue over a wide age range, compared with other gastrointestinal regions. Details are important because of natural human variability. We found age-related changes within the muscle, in the enteric and nociceptor innervation, and in the submucosa. Some involve all regions of colon, but the ascending colon appears more vulnerable. Changes can be cell- and sublayer-dependent. Mechanisms are unclear but may include development of "senescent-like" and associated inflammaging, perhaps associated with increased mucosal permeability to harmful luminal contents. In summary, reduced nociceptor innervation can explain diminished abdominal pain among the elderly. Degenerative changes within the colon wall may have little impact on symptoms and colonic functions, because of high "functional reserve," but are likely to facilitate the development of constipation during age-related challenges (e.g., lifestyle, disease, and medications), now operating against a reduced functional reserve.

Breast lymphedema following breast-conserving treatment for breast cancer: current status and future directions.

To examine the current evidence on breast lymphedema (BL) diagnosis and treatment after breast-conserving surgery, identify gaps in the literature, and propose future research directions. A comprehensive literature review was conducted using Ovid, PubMed, and Cochrane, including studies published between 2000 and 2023. References were reviewed manually for eligible studies. Inclusion criteria were as follows: patients who underwent breast conserving treatment (surgery ± radiation) for breast cancer, goals of the paper included analyzing or reviewing BL measurement with ultrasound or tissue dielectric constant, or BL treatment. Twenty-seven manuscripts were included in the review. There is variation in incidence, time course, and risk factors for BL. Risk factors for BL included breast size, primary and axillary surgery extent, radiation, and chemotherapy but require further investigation. Diagnostic methods for BL currently rely on patient report and lack standardized criteria. Tissue dielectric constant (TDC) and ultrasound (US) emerged as promising ambulatory BL assessment tools; however, diagnostic thresholds and validation studies with ICG lymphography are needed to establish clinical utility. The evidence base for treatment of BL is weak, lacking high-quality studies. The natural history of BL is not well defined. TDC and US show promise as ambulatory assessment tools for BL; however, further validation with lymphatic imaging is required. BL treatment is not established in the literature. Longitudinal, prospective studies including pre-radiation measurements and validating with lymphatic imaging are required. These data will inform screening, diagnostic criteria, and evidence-based treatment parameters for patients with BL after breast-conserving surgery and radiation.

A temporal decomposition method for identifying venous effects in task-based fMRI.

The spatial resolution of functional magnetic resonance imaging (fMRI) is fundamentally limited by effects from large draining veins. Here we describe an analysis method that provides data-driven estimates of these effects in task-based fMRI. The method involves fitting a one-dimensional manifold that characterizes variation in response timecourses observed in a given dataset, and then using identified early and late timecourses as basis functions for decomposing responses into components related to the microvasculature (capillaries and small venules) and the macrovasculature (large veins), respectively. We show the removal of late components substantially reduces the superficial cortical depth bias of fMRI responses and helps eliminate artifacts in cortical activity maps. This method provides insight into the origins of the fMRI signal and can be used to improve the spatial accuracy of fMRI.

Unconstrained multivariate EEG decoding can help detect lexical-semantic processing in individual children

In conditions such as minimally-verbal autism, standard assessments of language comprehension are often unreliable. Given the known heterogeneity within the autistic population, it is crucial to design tests of semantic comprehension that are sensitive in individuals. Recent efforts to develop neural signals of language comprehension have focused on the N400, a robust marker of lexical-semantic violation at the group level. However, homogeneity of response in individual neurotypical children has not been established. Here, we presented 20 neurotypical children with congruent and incongruent visual animations and spoken sentences while measuring their neural response using electroencephalography (EEG). Despite robust group-level responses, we found high inter-individual variability in response to lexico-semantic anomalies. To overcome this, we analysed our data using temporally and spatially unconstrained multivariate pattern analyses (MVPA), supplemented by descriptive analyses to examine the timecourse, topography, and strength of the effect. Our results show that neurotypical children exhibit heterogenous responses to lexical-semantic violation, implying that any application to heterogenous disorders such as autism spectrum disorder will require individual-subject analyses that are robust to variation in topology and timecourse of neural responses.

Effect of ABCB1 rs12720464 and rs1055302 polymorphisms in Chinese patients on the time course of action of rocuronium administered as a single dose.

To determine whether ABCB1 gene polymorphisms affect the time course of action of rocuronium in Chinese patients. This study included 105 unrelated Chinese patients undergoing general anesthesia with propofol, fentanyl, and rocuronium. Neuromuscular monitoring was performed with calibrated acceleromyography. Patients were allowed to recover spontaneously from the neuromuscular block. The time interval between the first maximum depression of the train of four (TOF) and spontaneous recovery TOF ratio of 0.25/0.7/0.8/0.9 was recorded. The Sequenom MassArray® single-nucleotide polymorphism (SNP) detection technology was used to detect the genotypes of the ABCB1 rs12720464, rs1055302. Demographic and non-genetic clinical data were also collected. In the present study, the mean time to spontaneous recovery of TOF ratio 0.8/0.9 in ABCB1 rs12720464 GG genotype was longer compared to that observed in ABCB1 rs12720464 AG genotype (56.77 ± 14.23 minutes vs. 49.50 ± 10.49 minutes, and 62.58 ± 18.16 minutes vs. 53.20 ± 12.56 minutes, respectively, p < 0.05). Further, the time to spontaneous recovery of TOF 0.7/0.8/0.9 in ABCB1 rs1055302 GG genotype was longer than that in ABCB1 rs1055302 AG genotype (52.00 ± 12.10 minutes vs. 44.83 ± 7.38 minutes, 55.96 ± 13.92 minutes vs. 46.83 ± 7.67 minutes, 61.66 ± 17.70 minutes vs. 49.50 ± 8.44 minutes, respectively, p < 0.05). In Chinese patients who were administered a single dose of rocuronium, the genetic variants ABCB1 rs12720464, and rs1055302 contribute to the individual< variability of time course of action.

Compression and Suppression of Shifting Receptive Field Activity in Frontal Eye Field Neurons

Before each saccade, neurons in frontal eye field anticipate the impending eye movement by showing sensitivity to stimuli appearing where the neuron's receptive field will be at the end of the saccade, referred to as the future field (FF) of the neuron. We explored the time course of this anticipatory activity in monkeys by briefly flashing stimuli in the FF at different times before saccades. Different neurons showed substantial variation in FF time course, but two salient observations emerged. First, when we compared the time span of stimulus probes before the saccade to the time span of FF activity, we found a striking temporal compression of FF activity, similar to compression seen for perisaccadic stimuli in human psychophysics. Second, neurons with distinct FF activity also showed suppression at the time of the saccade. The increase in FF activity and the decrease with suppression were temporally independent, making the patterns of activity difficult to separate. We resolved this by constructing a simple model with values for the start, peak, and duration of FF activity and suppression for each neuron. The model revealed the different time courses of FF sensitivity and suppression, suggesting that information about the impending saccade triggering suppression reaches the frontal eye field through a different pathway, or a different mechanism, than that triggering FF activity. Recognition of the variations in the time course of anticipatory FF activity provides critical information on its function and its relation to human visual perception at the time of the saccade.

Comparison of phenotypes of childhood wheeze and cough in 2 independent cohorts

Among children with wheeze and recurrent cough there is great variation in clinical presentation and time course of the disease. We previously distinguished 5 phenotypes of wheeze and cough in early childhood by applying latent class analysis to longitudinal data from a population-based cohort (original cohort). To validate previously identified phenotypes of childhood cough and wheeze in an independent cohort. We included 903 children reporting wheeze or recurrent cough from an independent population-based cohort (validation cohort). As in the original cohort, we used latent class analysis to identify phenotypes on the basis of symptoms of wheeze and cough at 2 time points (preschool and school age) and objective measurements of atopy, lung function, and airway responsiveness (school age). Prognostic outcomes (wheeze, bronchodilator use, cough apart from colds) 5 years later were compared across phenotypes. When using a 5-phenotype model, the analysis distinguished 3 phenotypes of wheeze and 2 of cough as in the original cohort. Two phenotypes were closely similar in both cohorts: Atopic persistent wheeze (persistent multiple trigger wheeze and chronic cough, atopy and reduced lung function, poor prognosis) and transient viral wheeze (early-onset transient wheeze with viral triggers, favorable prognosis). The other phenotypes differed more between cohorts. These differences might be explained by differences in age at measurements. Applying the same method to 2 different cohorts, we consistently identified 2 phenotypes of wheeze (atopic persistent wheeze, transient viral wheeze), suggesting that these represent distinct disease processes. Differences found in other phenotypes suggest that the age when features are assessed is critical and should be considered carefully when defining phenotypes.

Length of delay in seeking medical care by patients with heart failure symptoms and the role of symptom‐related factors: a narrative review

The delay in seeking timely medical care by patients with acute coronary syndrome and stroke is well established. Less is known about the delay in patients with heart failure (HF). Reducing the delay in seeking care and the early initiation of treatment is associated with improved outcomes in patients with HF. The purpose of this narrative review was to describe the length of the delay in seeking care for HF symptoms and identify symptom-related factors that contribute to the delay in seeking medical care. A literature search was conducted to identify English language studies that (i) describe the length of care-seeking delay for HF symptoms and/or (ii) identify symptom-related factors that contribute to delay in seeking medical care. The results of this review demonstrate that upon hospital admission patients report wide variations in median symptom time course from 2 h to 7 days from the onset of symptoms to hospital admission. The ability of patients to recognize, interpret, and appraise HF symptoms has been demonstrated to be limited. Symptom characteristics such as dyspnoea, oedema, orthopnoea, higher somatic awareness, higher symptom distress, nocturnal symptom onset, and the pattern of symptom onset were related to longer delay in care-seeking for HF symptoms. Furthermore, cognitive responses to HF may also play an important role in symptom appraisal. Delays in seeking care for HF symptoms have been shown to range from hours to days from symptom onset to hospital admission. Healthcare professionals should therefore be more vigilant in identifying high-risk individuals and educating them about the warning signs of HF. Moreover, access to outpatient chronic disease management programmes may have the potential to reduce these delays.

Quantification of porcine skin permeability in transdermal diffusion with a numerical model

Transdermal drug delivery system (TDDS) finds a variety of applications in drug delivery nowadays and is viewed as a potential method in controlled release of drug. Commonly known as a chemical enhancer in TDDS, urea alters the structure and composition of corneocyte and intracellular lipids, thus makes it easier for molecules to penetrate through stratum corneum, the major and outmost barrier layer of skin. In this research, however, urea itself is employed as a tracer diffusing through whole porcine skin in vitro. The diffusion process is recorded as the specific conductivity variation in time course. Concentration of urea is easily converted from its specific conductivity with aid of standard curves predetermined. Experimental results show the accumulation of tracer quantity diffusing through the skin sample as time proceeds. In parallel, a simple diffusion model is developed, attempting to describe this mass transport process in mathematical point of view. Output of the comparison between model data and experimental results generates the effective permeability of the whole skin, and quantifies the molecular mobility of the diffusing tracer. Permeability determined in this work is validated against literature data and discussed from molecular viewpoint theoretically. This study describes a combination of experiments and theory aiming at quantifying the transdermal permeation. Good agreement between model and experiment supports the efficacy of the approach and thus builds up a quantitative base for the upcoming researches seeking improvement of TDDS.

Explicit targeting of transformed cells by VSV in ovarian epithelial tumor-bearing Wv mouse models

Objective Current treatment options for epithelial ovarian cancer are limited and therapeutic development for recurrent and drug-resistant ovarian cancer is an urgent agenda. We investigated the potential use of genetically engineered Vesicular Stomatitis Virus (VSV) to treat ovarian cancer patients who fail to respond to available therapies. Specifically, we examined the toxicity to hosts and specificity of targeting ovarian tumors using a Wv ovarian tumor model. Methods We first tested recombinant VSV for oncolytic activity in a panel of human ovarian epithelial cancer, immortalized, and primary ovarian surface epithelial cells in culture. Then, we tested VSV oncolytic therapy using the immune competent Wv mice that develop tubular adenomas, benign tumor lesions derived from ovarian surface epithelial cells. Results The expression of GFP encoded by the recombinant VSV genome was detected in about 5% of primary ovarian surface epithelial cells (3 lines) up to 30 days without significantly altering the growth pattern of the cells, suggesting the lack of toxicity to the normal ovarian surface epithelial cells. However, VSV-GFP was detected in the majority (around 90%) of cells that are either “immortalized” by SV40 antigen expression or cancer lines. Some variation in killing time courses was observed, but all the transformed cell lines were killed within 3 days. We found that regardless of the inoculation route (intra bursal, IP, or IV), VSV specifically infected and replicated in the in situ ovarian tumors in the Wv mice without significant activity in any other organs and tissues, and showed no detectable toxicity. The epithelial tumor lesions were greatly reduced in VSV-targeted ovarian tumors in the Wv mice. Conclusions VSV oncolytic activity depends on a cell autonomous property distinguishing primary and transformed cells. The efficient oncolytic activity of VSV for the “immortalized” non-tumorigenic ovarian surface epithelial cells suggests that the selective specificity extends from pre-neoplastic to overt cancer cells. The results demonstrated the explicit targeting of ovarian epithelial tumors by VSV in immune competent, ovarian tumor-bearing mouse models, and further support the utility of VSV as an effective and safe anti-cancer agent.

Survival types of high mountain plants under extreme temperatures

Extreme temperatures are a main factor limiting plant growth in high mountain habitats. During winter, the risk of frost damage is highest at windblown and often snow-free sites. During summer, actively growing plants are particularly endangered by episodic cold spells, but also by short-term overheating. The current review gives an overview of extreme temperatures in the European Alps and observations of temperature damage on plants in their natural habitats. Furthermore, seasonal time courses of frost and heat resistance derived from laboratory tests on different plant growth forms are presented. Study species were the cushion plants Silene acaulis, Minuartia sedoides, Saxifraga oppositifolia and Carex firma collected on wind-exposed ridges; the rosette plant Soldanella alpina collected on snow-protected sites, and three Sempervivum species collected in xerothermic habitats. The temperature resistance of leaves, stems, rhizomes and roots were tested in two annual time courses. Frost treatments were conducted in controlled freezers by rapid cooling (10 K h −1, for current resistance) as well as by stepwise cooling (1–3 K h −1, for hardening capacity). Heat treatments followed a standardised procedure by exposing samples to heat for 30 min in hot water baths. The damage was visually estimated using the topographic tetrazolium test. During winter, cushion plants from exposed sites were fully hardened (LT 50 below −70 °C). Rosette plants, which are protected by a constant snow cover, survived temperatures of down to −25 °C. During the growing period, foliage and shoot tips of the investigated species were damaged at −5 to −8 °C (LT 50). Stems and rhizomes were only partially damaged by temperatures of −10 to −15 °C. Heat resistance in cushion plants generally reached 56–58 °C (LT 50), shoots and rhizomes of C. firma could reach 60 °C. Succulent plants like Sempervivum arachnoideum and S. tectorum from hot and dry microsites were the most heat resistant among the tested species (62–64 °C). The investigated mountain plant species showed highly varying resistance patterns, with variation in maximum hardening capability and seasonal time courses of resistance. Plants were capable of rapid adjustments to extreme temperatures, which is crucial for survival in a high mountain climate.

Whole Blood Multiple Electrode Aggregometry Is a Reliable Point-of-Care Test of Aspirin-Induced Platelet Dysfunction

Aspirin is one of the most commonly ingested over-the-counter drugs. In addition to its analgesic and antiinflammatory actions, it also potently inhibits platelet aggregation. Evaluation of aspirin-induced platelet dysfunction is relevant in various clinical situations, including during complex surgeries with high bleeding risk in individuals who have ingested aspirin. In this study, we examined the suitability of multiple electrode aggregometry (MEA) for time course assessment of the antiplatelet effects of a single oral dose of 500 mg aspirin. We also determined the applicability of this method in the point-of-care (POC) setting by comparing the results of the test after different time intervals after blood sampling. Twenty-four adult volunteers were enrolled in the study. After blood drawing at baseline, 500 mg aspirin was administered to all volunteers. Blood samples were taken at 4, 24, 56, 80, and 124 h after aspirin ingestion. At each time point, measurements were performed immediately and 30 and 60 min after drawing blood. Whole blood MEA was performed after stimulation with thrombin receptor activating peptide (TRAPtest, 32 microM) and arachidonic acid (ASPItest, 0.5 mM). Repeated measurement analysis of variance with a Bonferroni correction for multiple comparisons was performed to detect differences between time points. Assay imprecision was determined by calculating the coefficient of variation. The level of statistical significance was set to P < 0.05. Platelet aggregation by ASPItest was markedly decreased 4 h after aspirin intake. From the second day after aspirin intake, ASPItest values recovered with high interindividual variability, and 5 days after aspirin intake, ASPItest values did not differ significantly from baseline. TRAP-induced platelet aggregation (TRAPtest) showed no systematic changes during the study period. The resting time of the sample did not affect TRAPtest or ASPItest values. The coefficients of variation were 10% for the ASPItest and 7% for the TRAPtest. MEA reliably detected the effects of aspirin. Notably, 500 mg aspirin caused complete inhibition of arachidonic acid-induced platelet aggregation for 2 days in all volunteers. Aggregation returned to baseline values with a wide interindividual variation in time course by day 5. No resting time for the blood sample was required for ASPItest or TRAPtest. These assays can be implemented as real POC tests. The reproducibility of the assays studied here is within the range of modern POC analyzers.

Intravenous Ethanol Infusions Can Mimic the Time Course of Breath Alcohol Concentrations Following Oral Alcohol Administration in Healthy Volunteers

Our previous studies have used intravenous (IV) clamping methods to demonstrate that family history positive (FHP) subjects exhibit a greater initial response to alcohol than family history negative (FHN) subjects. These results differ from other studies of family history of alcoholism (FHA) influences, most of which have used an oral alcohol challenge, suggesting that the route of administration may influence both the response to alcohol and FHA-related differences in response. To examine this possibility, one approach would be to directly compare responses following oral and IV alcohol administration in the same subjects. There is, however, a 3- to 4-fold variance, between- and within-subjects, in the breath alcohol concentrations (BrACs) following oral alcohol administration. Thus, our objective was to characterize the between-subject variability in the time course of BrACs following oral alcohol administration in healthy volunteers and to develop an IV infusion method to mimic the BrAC-time course attained following oral alcohol in the same subject. This was a 2-session study in young adult, healthy, nondependent drinkers. In the first session, subjects ingested an oral dose of alcohol, based on total body water, to achieve a target peak BrAC of 80 mg%. In the second session, subjects received an IV infusion of ethanol designed to achieve the same BrAC time course as that achieved in the first session. The individualized infusion-rate profile was precomputed using a physiologically-based pharmacokinetic (PBPK) model for alcohol with model parameters adjusted to the individual's physiology. The peak BrACs (C(max)), times of peak BrAC (T(max)), and the areas under the BrAC vs. time curve (AUC) were compared between sessions to assess how closely the BrAC exposure during the IV infusion session mimicked the exposure following oral alcohol. The time course of BrACs following oral alcohol administration showed a high degree of between-subject variability. Mean C(max), T(max), and AUC did not differ by gender, indicating that calculation of oral doses based on total body water results in comparable BrAC-time courses, on average, for females and males. The IV infusion driven BrAC-time profiles demonstrated good fidelity to the BrAC-time curves resulting from oral alcohol: the mean %difference in C(max) and AUC were both 11%, while the mean %difference for T(max) was 27%. This degree of variability is less than half that seen across individuals following oral alcohol administration, which was substantial [coefficient of variation (%CV) ranging from 22 to 52%]. Despite the use of standardized doses and controlled experimental conditions, there was substantial between-subject variability in the BrAC time course following oral administration of alcohol. The PBPK-model-based infusion method can mimic the BrACs attained with oral alcohol for individual subjects. This method provides a platform to evaluate effects attributable to the route of administration on the response to alcohol, as well as the influence of determinants such as family history of alcoholism on the alcohol response.

Injury Measurement Properties of Serum Interleukin-6 Following Lumbar Decompression Surgery

Circulating interleukin-6 (IL-6) is frequently used to study surgical injury and inflammation. Measurement properties of serum IL-6 were examined following lumbar decompression surgery (LDS), including time course, sensitivity, and validity for detecting muscle trauma in comparison to the muscle cytoplasmic protein creatine kinase (CK). Seven women and seven men had serial blood samples taken in the preoperative waiting areas, immediately after surgery, at 6, 12, 24, 48 h, 4 d, and at 6 to 7 d. Lumbar surgeries were single level, decompression, with laminotomy. Time to peak serum IL-6 varied across individuals (range 6 to 48 h). However, the higher of two samples drawn within the sensitive time window (6 to 24 h) had a strong correlation with peak IL-6 (r = 0.99, P < 0.001). There was a moderate correlation between the rise in serum IL-6 and rise in serum CK, r = 0.56, P < 0.05. T-tests revealed that group mean IL-6 was significantly elevated at only one serial time point (6 h), whereas group mean CK was significantly elevated at three serial time points (6, 12, 24 h) and approached significant elevation as late as 48 h (P = 0.07). Women had lower CK concentrations at 6 and 24 h but gender differences on IL-6 were not statistically significant. The serum IL-6 response to LDS injury can be captured in a practical manner, despite individual variability in time course. Inclusion of CK measurement may improve sensitivity to the muscle trauma component of an overall injury.

Role of biogenic amines and cHH in the crustacean hyperglycemic stress response

In this study, we investigated (using bioassays and ELISA) the variation of cHH (crustacean hyperglycemic hormone) level in the eyestalks and hemolymph of Palaemon elegans (Rathke) (Decapoda, Caridea) following injection of serotonin (5-HT) and dopamine (DA) and correlated cHH profile with the variation in amount and time course of glycemia. 5-HT induced in P. elegans a rapid and massive release of cHH from the eyestalk into the hemolymph followed by hyperglycemia. On the contrary, DA did not significantly affect cHH release and hyperglycemia. In addition, we measured the level and variation of 5-HT in the eyestalk and hemolymph of P. elegans following copper contamination. The release of 5-HT from the eyestalk is very rapid and dose dependent. In the hemolymph, a peak of 5-HT occurs after 30 min, and again the circulating concentration of 5-HT is dose dependent on copper exposure. After 1 h, the level of 5-HT slowly decreases to basal level. The release of 5-HT from the eyestalk into the hemolymph after copper exposure precedes the release of cHH, confirming its role as a neurotransmitter acting on cHH neuroendocrine cells. The fact that copper induced a rapid and massive release of 5-HT from the eyestalk can explain its demonstrated role in inducing the release of cHH and the consequent hyperglycemia in intact but not eyestalkless animals.

Variation of crustacean hyperglycemic hormone (cHH) level in the eyestalk and haemolymph of the shrimpPalaemon elegansfollowing stress

This study investigates (by means of bioassays and ELISA using an antibody against recombinant cHH) the variation of cHH levels in the eyestalks and haemolymph of Palaemon elegans (Decapoda, Caridea) following exposure to various stresses (heavy metals and lipopolysaccharide), and correlates them with the variation in amount and time course of blood glucose. The dose-relationship between exposure to copper and quick release of cHH from the eyestalk into haemolymph was confirmed by variation of blood glucose with a dose-related hyperglycaemia, that peaked 2 h after immersion in contaminated seawater. Animals exposed to a sublethal concentration of mercury showed the same dose relation between toxicant, release of cHH from the eyestalk, increment of circulating hormone level and subsequent hyperglycaemia as observed for copper contamination. It is of note that although the highest lethal mercury concentration induced the release of cHH from the eyestalk into the haemolymph, it was not followed by a significant variation of blood glucose. Step doses of a bacterial contaminant [such as lipopolysaccharide (LPS) from E. coli injected into shrimps] confirmed the dose-relationship and convergent chain of events that bring about hyperglycaemia. These are the first data that relate the release of cHH from the eyestalk, the circulating hormone level and the consequent glycaemic response to stress. Moreover, they confirm the dose-related pathway that leads to variation of blood glucose as a quantitative biomarker of environmental quality, even at sublethal toxicant concentrations.

Cortisol concentrations in 12- to 18-Month-Old infants: stability over time, location, and stressor

Background Sparse information on early development of hypothalamic pituitary adrenal (HPA) axis responsivity in human infants limits our understanding of stress hormone regulation and vulnerability to psychopathology. We considered whether infant cortisol stress response (CSR) is a suitable endocrine phenotype for developmental stress research. Methods We assessed stability of key CSR parameters across time, location, and stressor through saliva samples taken before and then 20 and 40 min following exposure to two stressors administered 1 week apart in 27 infants aged 12 to 18 months. Time-matched home samples were collected to control for circadian rhythm and to evaluate baseline stability. Results Baseline cortisol concentrations, peak percent change, and area under the curve (AUC) were stable across time and stressors. Following both stressors, half the infants exhibited peak cortisol concentrations at 20 min poststress; half peaked at 40 min poststress. For 56% of the infants, peak response time was inconsistent across stressors. Conclusions In humans, baseline and CSR are stable by 12 to 18 months. Variation in CSR time course across stressors indicates that infant CSR should be sampled beyond 30 min. Results support using infant CSR, particularly as measured by AUC, as a valid endocrine phenotype for developmental stress research.

Morphological Changes in Salivary Glands Induced by Theophylline in Rats

Theophylline, a phosphodiesterase inhibitor, is known to induce enlargement of the salivary glands. This enlargement has been thought to be associated with enhanced cellular levels of cyclic AMP as a result of inhibition of phosphodiesterase. In the present study, to clarify the sequential changes in salivary glands following the administration of theophylline, a four-day repeated dose study and a single dose study were carried out in male rats, and the parotid and submaxillary glands were examined histologically. The results from the glands were almost identical. In the repeated dose study, the increased organ weight just before the last administration was reduced at 4 hr and then restored at 8 hr after the last administration. In the single dose study, a slight but significant increase in organ weight was observed at 24 hr after administration, following a transient reduction. Changes in acinus histology were consistent with these organ weight changes. Acinar cells were loaded with excessive secretory granules just before the last administration in the repeated dose study. After the last administration, granules were reduced at 4 hr, and then reaccumulated at 8 hr. Such time-course variability in the number of secretory granules corresponded well to clinically observed salivation. These results suggest that inhibition of phosphodiesterase is primarily involved in the discharge of secretory granules, and that the salivary hypertrophy previously reported is an adaptive response caused by the repeated stimulation of saliva secretion.

Smoking withdrawal dynamics in unaided quitters.

Considerable research shows that withdrawal severity is inconsistently related to smoking cessation outcomes. This may result from measurement problems or failure to scrutinize important dimensions of the withdrawal experience. Two recent studies demonstrated that withdrawal elevation and variations in the time course of withdrawal were related to relapse in smokers treated with the nicotine patch (T. M. Piasecki, M. C. Fiore, & T. B. Baker, 1998). This article reports a conceptual replication and extension of those findings in unaided quitters. Evidence for temporal heterogeneity was found across different types of withdrawal symptoms. Patterns or slopes of affect and urge reports over time predicted smoking status at follow-up, as did mean elevation in withdrawal symptoms. These results suggest that affect and urge withdrawal symptoms make independent contributions to relapse and that relapse is related to both symptom severity and trajectory.

Structured lipids: Lipase‐catalyzed interesterification of tricaproin and trilinolein

AbstractStructured lipids were synthesized by interesterification of trilinolein and tricaproin with sn‐1,3‐specific (IM 60) and nonspecific (SP 435) lipases. The interesterification reaction was performed by incubating a 1:2 mole ratio of trilinolein and tricaproin in 3 mL hexane at 45°C for the IM 60 lipase from Rhizomucor miehei, and at 55°C for the SP 435 lipase from Candida antarctica. Reaction products were analyzed by reverse‐phase high‐performance liquid chromatography with an evaporative light‐scattering detector. The fatty acids at the sn‐2 position were identified after pancreatic lipase hydrolysis and analysis with a gas chromatograph. IM 60 lipase produced 53,5 mol% dicaproyllinolein (total carbon number = C33) and 22.2% monocaproyldilinolein (C45). SP 435 lipase produced 41% C33 and 18% C45. When caproic acid was used in place of tricaproin as the acyl donor, the IM 60 lipase produced 62.9% C33. The effects of variation in mole ratio, temperature, added water, solvent polarity, and time course on the interesterification reaction were also investigated. In the absence of organic solvent, IM 60 lipase produced 52.3% C33.