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Energy expenditure in the obese: is there a thrifty gene?

Seven to eight thousand Pima Indians are presently living in the southwestern desert of Arizona. The prevalence of type II diabetes in this population exceeds 45% and more than 75% of the Pimas are obese. In 1962, Neel proposed that obesity in populations like the Pima Indians might be the expression of a "thrifty gene" which becomes detrimental with progress. Since 1982, longitudinal studies have been conducted including measurements of metabolic rate in 200 non-diabetic Pima Indians and have shown that 1) at any given body weight and body composition, there is quite a large variability in the resting metabolic rate which is not accounted for by intra-individual variability or errors of the methods; 2) metabolic rate after adjustment for body composition and body weight is a familial trait; 3) a low metabolic rate is a risk factor for body weight gain; 4) in response to body weight gain, there is a "normalization" of the resting metabolic rate. These studies are the first showing that a "thrifty" metabolic rate can play a role in the development of obesity.

Arizona↗

How does a fur seal mother recognize the voice of her pup? An experimental study of Arctocephalus tropicalis.

In the subantarctic fur seal Arctocephalus tropicalis, mothers leave their pups during the rearing period to make long and frequent feeding trips to sea. When a female returns from the ocean, she has to find her pup among several hundred others. Taking into account both spectral and temporal domains, we investigated the individual vocal signature occurring in the 'female attraction call' used by pups to attract their mother. We calculated the intra- and inter-individual variability for each measured acoustic cue to isolate those likely to contain information about individual identity. We then tested these cues in playback experiments. Our results show that a female pays particular attention to the lower part of the signal spectrum, the fundamental frequency accompanied by its first two harmonics being sufficient to elicit reliable recognition. The spectral energy distribution is also important for the recognition process. Of the temporal features, frequency modulation appears to be a key component for individual recognition, whereas amplitude modulation is not implicated in the identification of the pup's voice by its mother. We discuss these results with respect to the constraints imposed on fur seals by a colonial way of life.

Animals↗

College factors that influence drinking.

OBJECTIVE: The purpose of this article is to examine the aspects of collegiate environments, rather than student characteristics, that influence drinking. Unfortunately, the existing literature is scant on this topic. METHOD: A literature review of articles primarily published within the last 10 years, along with some earlier "landmark" studies of collegiate drinking in the United States, was conducted to determine institutional factors that influence the consumption of alcohol. In addition, a demonstration analysis of Core Alcohol and Drug Survey research findings was conducted to further elucidate the issues. RESULTS: Several factors have been shown to relate to drinking: (1) organizational property variables of campuses, including affiliations (historically black institutions, women's institutions), presence of a Greek system, athletics and 2- or 4-year designation; (2) physical and behavioral property variables of campuses, including type of residence, institution size, location and quantity of heavy episodic drinking; and (3) campus community property variables, including pricing and availability and outlet density. Studies, however, tend to look at individual variables one at a time rather than in combination (multivariate analyses). Some new analyses, using Core Alcohol and Drug Survey data sets, are presented as examples of promising approaches to future research. CONCLUSIONS: Given the complexities of campus environments, it continues to be a challenge to the field to firmly establish the most compelling institutional and environmental factors relating to high-risk collegiate drinking.

Alcohol Drinking↗

Striatal recruitment during an implicit sequence learning task as measured by functional magnetic resonance imaging.

Prior research has repeatedly implicated the striatum in implicit sequence learning; however, imaging findings have been inconclusive with respect to the sub-territories and laterality involved. Using functional magnetic resonance imaging (fMRI), we studied brain activation profiles associated with performance of the serial reaction time task (SRT) in 10 normal right-handed males. Behavioral results indicate that significant implicit learning occurred, uncontaminated by significant explicit knowledge. Concatenated fMRI data from the entire cohort revealed significant right-lateralized activation in both the caudate and putamen. Analysis of fMRI data from individual subjects showed inter-individual variability as to the precise territories involved, including right as well as left caudate and putamen. Interestingly, all seven subjects who manifested robust learning effects exhibited significant activation within the putamen. Moreover, among those seven subjects, the magnitude of signal intensity change within the putamen correlated significantly with the magnitude of reaction time advantage achieved. These findings demonstrate right-sided striatal activation across subjects during implicit sequence learning, but also highlight interindividual variability with respect to the laterality and striatal subterritories involved. In particular, results from individual subjects suggest that, during the SRT, the reaction time advantage garnered via implicit sequence learning might be predominantly associated with activity within the putamen.

Adult↗

Patterns of p73 N-terminal isoform expression and p53 status have prognostic value in gynecological cancers.

The goal of this study was to determine whether patterns of expression profiles of p73 isoforms and of p53 mutational status are useful combinatorial biomarkers for predicting outcome in a gynecological cancer cohort. This is the first such study using matched tumor/normal tissue pairs from each patient. The median follow-up was over two years. The expression of all 5 N-terminal isoforms (TAp73, DeltaNp73, DeltaN'p73, Ex2p73 and Ex2/3p73) was measured by real-time RT-PCR and p53 status was analyzed by immunohistochemistry. TAp73, DeltaNp73 and DeltaN'p73 were significantly upregulated in tumors. Surprisingly, their range of overexpression was age-dependent, with the highest differences delta (tumor-normal) in the youngest age group. Correction of this age effect was important in further survival correlations. We used all 6 variables (five p73 isoform levels plus p53 status) as input into a principal component analysis with Varimax rotation (VrPCA) to filter out noise from non-disease related individual variability of p73 levels. Rationally selected and individually weighted principal components from each patient were then used to train a support vector machine (SVM) algorithm to predict clinical outcome. This SVM algorithm was able to predict correct outcome in 30 of the 35 patients. We use here a mathematical tool for pattern recognition that has been commonly used in e.g. microarray data mining and apply it for the first time in a prognostic model. We find that PCA/SVM is able to test a clinical hypothesis with robust statistics and show that p73 expression profiles and p53 status are useful prognostic biomarkers that differentiate patients with good vs. poor prognosis with gynecological cancers.

Age Factors↗

Longitudinal studies of fetal growth with the use of dynamic image ultrasonography.

To characterize the growth of individual fetuses, serial measurements of the crown-rump length (CRL), biparietal diameter (BPD), head circumference (HC), and abdominal circumference (AC) were made at specified intervals of 2 to 3 weeks (between 6 to 8 weeks [conceptual age] and delivery) in 20 normal fetuses with known dates of conception. Values for the HC-AC ratio and the estimated fetal weight were also obtained from these data. Measurements of CRL were similar to those reported previously, except in those cases in which the follicular phase was prolonged or the fetal growth potential was reduced. Mathematical modeling demonstrated that the linear-cubic model was optimal for the BPD and HC growth curves, the linear model for the AC, and the linear-quadratic model for fetal weight. The HC-AC ratio could not be modeled adequately because of significant individual variability. Optimal models for average longitudinal growth curves were determined for the BPD, HC, AC, and fetal weight from individual growth curves. These average longitudinal curves were similar in shape, mean values, and variability to those obtained in previous cross-sectional studies. Statistical analysis indicated that the coefficients of the average longitudinal curves are not likely to change by more than 5% to 15% if the size of the sample is increased very significantly. These results indicate that the average longitudinal growth curves are good estimators of the true population growth curves.

Adult↗

Drugs and sport. Research findings and limitations.

Many types of drugs are used by athletes to improve performance. This paper reviews the literature on 3 categories of drugs: those that enhance performance as stimulants (amphetamines, ephedrine, and cocaine), those that are used to reduce tremor and heart rate (beta-blockers) and those involved in bodyweight gain or loss (anabolic-androgenic steroids, growth hormone, beta 2-agonists, and diuretics). Limitations of research on these drugs as they relate to performance enhancement are also discussed. The numerous studies that have assessed the effects of amphetamines on performance report equivocal results. This may be due to the large interindividual variability in the response to the drug and the small sample sizes used. Most studies, however, show that some individuals do improve exercise performance when taking amphetamines, which may be attributed to their role in masking fatigue. As a stimulant, ephedrine has not been found to improve performance in the few studies available. More recently, ephedrine has been purported to be effective as a fat burner and used by athletes to maintain or improve muscle mass. Although research on individuals with obesity supports the use of ephedrine for fat loss, no studies have been done on athletes. The few studies of cocaine and exercise suggest that little to no performance gains are incurred from cocaine use. Moreover, the sense of euphoria may provide the illusion of better performance when, in actuality, performance was not improved or was impaired. beta-Blockers have been found to reduce heart rate and tremor and to improve performance in sports that are not physiologically challenging but require accuracy (e.g. pistol shooting). However, there is evidence that some individuals may be high responders to beta-blockers to the extent that their heart rate response is so blunted as to impair performance. Although equivocal, several studies have reported that anabolic-androgenic steroids increase muscle size and strength. However, most studies are not well controlled and use insufficient drug doses. One recent well controlled study did find an increase in muscle mass and strength with supraphysiological doses, and the improvements were greater in participants who were also resistance training. There is little information available on the effects of growth hormone on muscle mass or performance in athletes, although data suggest that growth hormone administration does not increase muscle protein synthesis. beta 2-Agonists, such as clenbuterol and salbutamol, when administered orally appear to improve muscular strength due to their potential role in increasing muscle mass. However, studies have not been done using athletes. Diuretics results in a loss of body water and hence bodyweight that can be advantageous for sports with strict bodyweight classifications. There is insufficient evidence on possible performance decrements in the field that could result from dehydration induced by the diuretics. Overall, the most significant concern in studies of drug use is the large inter-individual variability in responses to a drug. Further studies are needed to understand why some individuals are more responsive than others and to assess whether the responses are consistent for a given individual. Most studies of drug effectiveness have not used athletes. The effectiveness of many drugs may be reduced in highly trained athletes because there is a lower margin for improvement.

Adrenergic beta-Antagonists↗

Relationship between unbound plasma concentrations and various psychomotor and subjective effects after intakes of diazepam and flunitrazepam.

Unbound plasma concentrations of diazepam and flunitrazepam were related to psychomotor and subjective effects of the two drugs. The interindividual variability in plasma protein binding of both diazepam (98.5 +/- 0.14%) and flunitrazepam (84.5 +/- 1.2%) was relatively small, and high correlations were therefore observed between the individual unbound and total drug plasma concentrations after a particular dose. However, poor correlations were seen between individual unbound drug plasma concentrations and psychomotor or subjective effects. This observation indicates that factors other than individual variability in drug plasma concentration, account for the pronounced individual differences in, for example, psychomotor impairment frequently observed after intake of benzodiazepines. Furthermore, based on a linear relationship between unbound drug plasma concentrations and increase in either complex choice or simple reaction time, the potency of flunitrazepam was calculated to be about seven times higher than the potency of diazepam. This is approximately two times higher than expected from the reported in vitro affinity of the two drugs for the benzodiazepine receptor. This finding may indicate that flunitrazepam may have a higher apparent in vivo intrinsic efficacy than diazepam when assessed by psychomotor impairment.

Adult↗

Population distribution of placental benzo(a)pyrene metabolism in smokers.

Human placental microsomes isolated from term placentas derived from nonsmoking women and women smoking 1 to 40 cigarettes a day were analyzed for the metabolism of benzo(a)pyrene measured as various metabolites by HPLC and/or as aryl hydrocarbon hydroxylase (AHH)6 activity. In accordance with other reports, AHH activity was several times higher in smokers than in nonsmokers. Regression analysis on 13 different placental tissues from women smoking from 1 to 40 cigarettes demonstrated a high correlation (r = 0.8 to 0.9) between AHH activity (or the formation of benzo(a)pyrene phenols resolved by HPLC) versus the formation of the procarcinogenic benzo(a)pyrene-7,8-diol. Subsequent studies on placentas derived from 67 women who smoked 10 to 40 cigarettes per day demonstrated a definite dose-response relationship between AHH activity and the number of cigarettes smoked/day. The dose-response curve was sigmoidal in shape; however, when the data were plotted on a semi-log scale the curve assumed a linear shape, reaching saturation of AHH induction beyond 20 to 25 cigarettes/day. While mean AHH activity was dependent upon the number of cigarettes smoked/day, considerable interindividual variability in AHH (ranging more than 1,000-fold in some cases) was observed among individuals with comparable smoking histories, i.e. smoking the same number of cigarettes. Population distribution suggested clustering of the population in the low-AHH-activity region while cord-blood thiocyanate analysis and twin studies suggested that genetic factors contributed to a major portion of the inter-individual variability in AHH activity observed among smokers.

Aryl Hydrocarbon Hydroxylases↗

Imputation for incomplete high-dimensional multivariate normal data using a common factor model.

It is common in applied research to have large numbers of variables measured on a modest number of cases. Even with low rates of missingness on individual variables, such data sets can have a large number of incomplete cases. Here we present a new method for handling missing continuously scaled items in multivariate data, based on extracting common factors to reduce the number of covariance parameters to be estimated in a multivariate normal model. The technique is compared in several simulation settings to available-case analysis and to a multivariate normal model with a ridge prior. The method is also illustrated on a study with over 100 variables evaluating an emergency room intervention for adolescents who attempted suicide.

Humans↗

hOGG1 SER326CYS genetic polymorphism in a Turkish population.

Oxidative DNA damage, caused by either endogenous or exogenous sources of reactive oxygen species (ROS), has been linked to aging, chronic degenerative diseases, inflammatory diseases and cancers. 8-Hydroxydeoxyguanine (8-OHdG) is a major lesion produced by ROS. Among various types of DNA base modifications, 8-OHdG has been the most widely studied and is considered a key biomarker of oxidative DNA damage. Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is a key component of the base excision repair (BER) pathway and catalyzes the removal of 8-OHdG. Ethnic and inter-individual differences in hOGG1 activity and several kinds of polymorphisms at the hOOG1 gene locus have been observed in the different populations studied so far. Since no information is available on the inter-individual variability of the hOGG1 genotype in the Turkish population, we genotyped 206 healthy, unrelated Turkish individuals. The allelic frequencies of the hOGG1 gene in the Turkish population were found to be 0.50, 0.41 and 0.09 (Ser/Ser, Ser/Cys and Cys/Cys, respectively). Our results are similar to those for Caucasians studied previously but are different from Asian populations. It seems that there is a growing need for extensive genotype studies with respect to the hOGG1 gene due to its importance to various types of cancer and to smoking habits.

Adult↗

A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy.

The objective of this study was to investigate the central processing of dynamic mechanical allodynia in patients with mononeuropathy. Regional cerebral blood flow, as an indicator of neuronal activity, was measured with positron emission tomography. Paired comparisons were made between three different states; rest, allodynia during brushing the painful skin area, and brushing of the homologous contralateral area. Bilateral activations were observed in the primary somatosensory cortex (S1) and the secondary somatosensory cortex (S2) during allodynia compared to rest. The S1 activation contralateral to the site of the stimulus was more expressed during allodynia than during innocuous touch. Significant activations of the contralateral posterior parietal cortex, the periaqueductal gray (PAG), the thalamus bilaterally and motor areas were also observed in the allodynic state compared to both non-allodynic states. In the anterior cingulate cortex (ACC) there was only a suggested activation when the allodynic state was compared with the non-allodynic states. In order to account for the individual variability in the intensity of allodynia and ongoing spontaneous pain, rCBF was regressed on the individually reported pain intensity, and significant covariations were observed in the ACC and the right anterior insula. Significantly decreased regional blood flow was observed bilaterally in the medial and lateral temporal lobe as well as in the occipital and posterior cingulate cortices when the allodynic state was compared to the non-painful conditions. This finding is consistent with previous studies suggesting attentional modulation and a central coping strategy for known and expected painful stimuli. Involvement of the medial pain system has previously been reported in patients with mononeuropathy during ongoing spontaneous pain. This study reveals a bilateral activation of the lateral pain system as well as involvement of the medial pain system during dynamic mechanical allodynia in patients with mononeuropathy.

Adult↗

Visual preferences of students with profound mental retardation and healthy, full-term infants.

Thirty students with profound mental retardation (age range: 3-5 to 19-11) and 30 healthy, full-term infants (5-8 months) were shown 12 stimuli, three times each. Four patterned stimuli were presented one to a card and each pattern appeared in black-and-white, black-and-yellow, and red-and-yellow. Both groups looked significantly longer at face patterns than other patterns. Students with profound mental retardation looked longer at black-and-white patterns than other color combinations. Infants looked longer at red and yellow cards than did students with profound mental retardation. The measurement method was practical, reliable, and sensitive to both within and between group differences. Results from this assessment method may help determine the most salient visual stimuli for evoking active-alert states for students with profound mental retardation. Individual variability was evident in the data, which demonstrates the importance of examining preferences for each individual when planning intervention. Implications for future research and intervention are discussed.

Child↗

Individualized correction factors in the preselection of hearing aids.

This study investigated three issues involving corrections for individual ear acoustics in hearing aid prescriptions: (a) the extent to which inconsistencies in the sound-field reference position can affect comparative corrections for the real-ear unaided response (REUR); (b) the extent to which individual variability in the real-ear-to-coupler level difference (RECD) supports the use of individual measurements as opposed to an average-ear estimate; and (c) the adequacy of using KEMAR estimates of the effects of the location of the hearing aid microphone. In Experiment 1, KEMAR REURs using over-the-ear and under-the-ear reference positions were compared with KEMAR REURs using a center-of-head reference position. Maximum differences of 4-9 dB were found in the 1500- to 5000-Hz range, depending on test conditions. In Experiment 2, the ear canal response of an insert earphone was compared to the 2-cc coupler response of the same earphone to calculate the RECD. Individual RECDs for a population of hearing aid candidates were compared to the RECD for KEMAR. For 8 of the 15 subjects (9 of 18 ears), the RECD was more than 4 dB different from KEMAR at two or more third-octave frequencies between 500 and 4000 Hz. In Experiment 3, the effect of the location of the hearing aid microphone for in-the-ear (ITE) and in-the-canal (ITC) locations was compared with the over-the-ear (OTE) location for 18 ears and for KEMAR. The effects varied across individual ears, but all ears and KEMAR showed positive gain in the high frequencies for the ITE and ITC locations. The relevance of these results to hearing aid prescription practices is discussed.

Adult↗

The effect of ciprofloxacin on theophylline pharmacokinetics in healthy subjects.

1. The mechanism of the interaction between ciprofloxacin and theophylline was investigated in nine healthy subjects. 2. Subjects were given a single oral dose of theophylline (3.4 mg kg-1), before and after 60 h of ciprofloxacin therapy at a dose of 500 mg twice daily. 3. Ciprofloxacin reduced the oral clearance of theophylline by 19% (-7.73 +/- 6.42 ml kg-1 h-1 (95% confidence limits -12.66, -2.79)). Some subjects (group A, n = 4) showed little decrease in clearance (mean 4.4%; -1.6 +/- 0.7 ml kg-1 h-1 (-2.6, 0.5)), whereas others (group B, n = 5) showed a marked decrease (mean 30%; -12.7 +/- 3.7 ml kg-1 h-1 (-17.2, -8.1)). 4. Comparing groups A and B, the decrease in oral clearance of theophylline in group B could not be ascribed to differences in the AUC of ciprofloxacin. Group A subjects showed only slight inhibition of 1-demethylation (-12.8 +/- 5.5% (-21.5, -4.0)), while group B subjects showed a significantly greater inhibition of 1-demethylation (-49.9 +/- 9.8% (-62.1, -37.7)), 3-demethylation (-44.8 +/- 8.6% (-55.4, -34.1)) and 8-hydroxylation (-27.0 +/- 3.7% (-31.6, -22.4)). 5. The results suggest that inter-individual variability in the inhibition of theophylline metabolism by ciprofloxacin can be attributed to inter-individual differences in the level of CYP1A2 expression and/or in the degree of inhibition of hepatic CYP1A2 and CYP3A4. 6. The interaction between ciprofloxacin and theophylline can be clinically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Variations in health status within and between socioeconomic strata.

OBJECTIVES: To analyse the variability in health status within as well as between socioeconomic groups. What is the range of individual variability in the health effects of socioeconomic status? Is the adverse effect of lower socioeconomic status uniform across the entire distribution of health status? DESIGN: Nationally representative telephone survey of the US population in 1996. SETTING: 60 US metropolitan and rural areas. PARTICIPANTS: 47 076 adult respondents to the community tracking study. MAIN OUTCOME MEASURES: Self rated physical and mental health status, measured by the Short Form-12 instrument. RESULTS: There is considerable variability in self rated health within socioeconomic strata and that variability increases in a step-wise fashion at each lower stratum of income. Most of the increased variability is accounted for by changes in the middle and lower (10th, 25th, and 50th centiles) rather than the upper (75th and 90th) portions of the distribution. A resilient subgroup of lower socioeconomic status people seems to maintain excellent self rated health throughout life, while a more vulnerable lower socioeconomic status group experiences rapid deterioration in health status as people reach middle age. CONCLUSIONS: Within the population level social structuring of health there are differences in individual resilience and vulnerability that are amenable to further exploration and potential modification.

Adolescent↗

Epidemiology in anaesthesia: a method for predicting hospital mortality.

Data on 13 043 operations were abstracted from 108 878 anaesthetic records in the Cardiff Anaesthetic Record System. Nine groups of surgical operations with high mortality in hospital were identified. These records were analysed using a logistic regression model to determine the probability of death in hospital. Variables included in the model were age, sex, elective or emergency operation and five intercurrent diseases. The significance of individual variables was assessed: age was the most important single variable in six of the nine operation groups. The model was used to calculate the risk of death in hospital for individuals with specific characteristics. With further development, this technique might be used by clinicians at other centres to predict the outcome for patients under their care.

Age Factors↗

A correlation between low back pain and associated factors: a study involving 772 patients who had undergone general physical examination.

Many factors are associated with the development of low back pain. Among them, exercise, obesity, smoking, age, educational level and stress are the most common. This study examined the association of these factors with low back pain. An additional aim was to determine a procedure for preventing low back pain. This study analyzed the responses to a questionnaire sent to 772 individuals who had undergone a medical examination at this hospital in 2003 and excluded the individuals who had shown symptoms or their test results indicated a particular disease. Assuming that there were no variables, individuals who exercised regularly 3-4 times per week would have a lower chance of having low back pain than those who did not exercise regularly. The analysis revealed that individuals with a college degree or higher education have a lower chance of experiencing low back pain than those with only a high school education or even college drop-outs. When the other variables were constant, age, extent of obesity (body mass index), smoking and level of stress were not found to affect the development of low back pain. The level of education was associated with the development of low back pain. However, regular exercise 3-4 times per week or more would be most effective in reducing the incidence and duration of low back pain.

Adolescent↗