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1.
Hemispheric lateralization constitutes a core architectural principle of human brain organization underlying cognition, often argued to represent a stable, trait-like feature. However, emerging evidence underlines the inherently dynamic nature of brain networks, in which time-resolved alterations in functional lateralization remain uncharted. Integrating dynamic network approaches with the concept of hemispheric laterality, we map the spatiotemporal architecture of whole-brain lateralization in a large sample of high-quality resting-state fMRI data (N = 991, Human Connectome Project). We reveal distinct laterality dynamics across lower-order sensorimotor systems and higher-order associative networks. Specifically, we expose 2 aspects of the laterality dynamics: laterality fluctuations (LF), defined as the standard deviation of laterality time series, and laterality reversal (LR), referring to the number of zero crossings in laterality time series. These 2 measures are associated with moderate and extreme changes in laterality over time, respectively. While LF depict positive association with language function and cognitive flexibility, LR shows a negative association with the same cognitive abilities. These opposing interactions indicate a dynamic balance between intra and interhemispheric communication, i.e., segregation and integration of information across hemispheres. Furthermore, in their time-resolved laterality index, the default mode and language networks correlate negatively with visual/sensorimotor and attention networks, which are linked to better cognitive abilities. Finally, the laterality dynamics are associated with functional connectivity changes of higher-order brain networks and correlate with regional metabolism and structural connectivity. Our results provide insights into the adaptive nature of the lateralized brain and new perspectives for future studies of human cognition, genetics, and brain disorders.

Hemispheric lateralization constitutes a core architectural principle of human brain organization, often argued to represent a stable, trait-like feature, but how does this fit with our increasing appreciation of the inherently dynamic nature of brain networks? This neuroimaging study reveals the dynamic nature of functional brain lateralization at resting-state and its relationship with language function and cognitive flexibility.  相似文献   

2.

Background

Auditory laterality is suggested to be characterized by a left hemisphere dominance for the processing of conspecific communication. Nevertheless, there are indications that auditory laterality can also be affected by communicative significance, emotional valence and social recognition.

Methodology/Principal Findings

In order to gain insight into the effects of caller characteristics on auditory laterality in the early primate brain, 17 gray mouse lemurs were tested in a head turn paradigm. The head turn paradigm was established to examine potential functional hemispheric asymmetries on the behavioral level. Subjects were presented with playbacks of two conspecific call types (tsak calls and trill calls) from senders differing in familiarity (unfamiliar vs. familiar) and sex (same sex vs. other sex). Based on the head turn direction towards these calls, evidence was found for a right ear/left hemisphere dominance for the processing of calls of the other sex (Binomial test: p = 0.021, N = 10). Familiarity had no effect on the orientation biases.

Conclusions/Significance

The findings in this study support the growing consensus that auditory laterality is not only determined by the acoustic processing of conspecific communication, but also by other factors like the sex of the sender.  相似文献   

3.
It is well known that circadian rhythms modulate human physiology and behavior at various levels. However, chronobiological data concerning mental and sensorimotor states of motor actions are still lacking in the literature. In the present study, we examined the effects of time-of-day on two important aspects of the human motor behavior: prediction and laterality. Motor prediction was experimentally investigated by means of imagined movements and laterality by comparing the difference in temporal performance between right and left arm movements. Ten healthy participants had to actually perform or to imagine performing arm-pointing movements between two targets at different hours of the day (i.e., 08:00, 11:00, 14:00, 17:00, 20:00, and 23:00?h). Executed and imagined movements were accomplished with both the right and left arm. We found that both imagined and executed arm pointing movements significantly fluctuated through the day. Furthermore, the accuracy of motor prediction, investigated by the temporal discrepancy between executed and imagined movements, was significantly better in the afternoon (i.e., 14:00, 17:00, and 20:00?h) than morning (08:00 and 11:00?h) and evening (23:00?h). Our results also revealed that laterality was not stable throughout the day. Indeed, the smallest temporal differences between the two arms appeared at 08:00 and 23:00?h, whereas the largest ones occurred at the end of the morning (11:00?h). The daily variation of motor imagery may suggest that internal predictive models are flexible entities that are continuously updated throughout the day. Likewise, the variations in temporal performance between the right and the left arm during the day may indicate a relative independence of the two body sides in terms of circadian rhythms. In general, our findings suggest that cognitive (i.e., mental imagery) and motor (i.e., laterality) states of human behavior are modulated by circadian rhythms. (Author correspondence: )  相似文献   

4.

Background

According to decades of research on affective motivation in the human brain, approach motivational states are supported primarily by the left hemisphere and avoidance states by the right hemisphere. The underlying cause of this specialization, however, has remained unknown. Here we conducted a first test of the Sword and Shield Hypothesis (SSH), according to which the hemispheric laterality of affective motivation depends on the laterality of motor control for the dominant hand (i.e., the “sword hand," used preferentially to perform approach actions) and the nondominant hand (i.e., the “shield hand," used preferentially to perform avoidance actions).

Methodology/Principal Findings

To determine whether the laterality of approach motivation varies with handedness, we measured alpha-band power (an inverse index of neural activity) in right- and left-handers during resting-state electroencephalography and analyzed hemispheric alpha-power asymmetries as a function of the participants'' trait approach motivational tendencies. Stronger approach motivation was associated with more left-hemisphere activity in right-handers, but with more right-hemisphere activity in left-handers.

Conclusions

The hemispheric correlates of approach motivation reversed between right- and left-handers, consistent with the way they typically use their dominant and nondominant hands to perform approach and avoidance actions. In both right- and left-handers, approach motivation was lateralized to the same hemisphere that controls the dominant hand. This covariation between neural systems for action and emotion provides initial support for the SSH.  相似文献   

5.

Objective

Decision making is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential decisions are made just as cognitive function declines. Increasing evidence suggests that older adults, even those without dementia, often make poor decisions and are selectively vulnerable to scams. To date, however, the factors associated with poor decision making in old age are unknown. The objective of this study was to test the hypothesis that poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment.

Methods

Participants were 420 non-demented persons from the Memory and Aging Project, a longitudinal, clinical-pathologic cohort study of aging in the Chicago metropolitan area. All underwent repeated cognitive evaluations and subsequently completed assessments of decision making and susceptibility to scams. Decision making was measured using 12 items from a previously established performance-based measure and a self-report measure of susceptibility to scams.

Results

Cognitive function data were collected over an average of 5.5 years prior to the decision making assessment. Regression analyses were used to examine whether the prior rate of cognitive decline predicted the level of decision making and susceptibility to scams; analyses controlled for age, sex, education, and starting level of cognition. Among 420 persons without dementia, more rapid cognitive decline predicted poorer decision making and increased susceptibility to scams (p’s<0.001). Further, the relations between cognitive decline, decision making and scams persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or even mild cognitive impairment).

Conclusions

Poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment, those widely considered “cognitively healthy.” These findings suggest that even very subtle age-related changes in cognition have detrimental effects on judgment.  相似文献   

6.
Summary The proximal truncus arteriosus of the lizard Trachydosaurus rugosus was studied with light-, fluorescence and electron-microscopical techniques. Three vessels comprised the truncus: the pulmonary, left aortic, and caroticoaortic arteries. Right and left truncal nerves, each derived from the ipsilateral vagus nerve, innervated the truncus, particularly its proximal 3 mm.Ultrastructurally, the nerves had a variety of appearances: some were clearly adrenergic, c-type or p-type. A number of profiles contained large numbers of mitochondria and were classified as sensory. Some profiles defied exact classification, having characteristics common to two different types of profile.Within the outer medial layers, profiles up to 7 m in diameter were found. These contained large numbers of mitochondria, myelin bodies and structures intermediate between the two. In addition, the profiles contained large amounts of glycogen and small numbers of vesicles. These nerve fibres were classified as baroreceptors, since they closely resemble carotid sinus and aortic arch baroreceptors in mammals.Large numbers of chromaffin cells were found, particularly in the common wall of the pulmonary and left aortic arteries. Many of these cells emitted a long tapering process, which sometimes entered a nearby nerve bundle. Sensory, p-type and c-type profiles, but not adrenergic profiles, made extensive close contacts with chromaffin cells.  相似文献   

7.

Background

Natural menopause is always accompanied by specific signs and symptoms, suggesting physiological changes in this peoriod. However, no systematic study has assessed the changes at molecular level in the ovaries during the menopausal transition so far. This study integrated quantitative proteome and acetyl-proteome to comprehensively uncover the changes of ovarian protein and protein-acetylation profiles in this transitional period. The findings would provide novel insights into the biology of menopause and help relieve and treat the associated signs and symptoms, further improving the women’s health care.

Methods

Freshly thawed ovarian tissue samples obtained from premenopausal and postmenopausal women were assessed with Tandem Mass Tags for the quantitative analysis of the global profile and acetyl-proteomes by 2-dimensional separation and LC–MS/MS.

Results

Comprehensively, 4210 types of protein, with 3551 types quantifiable were detected. 3047 acetylated sites in 1583 types of protein with 2256 quantifiable in 1248 proteins were detected. By comparing the global and acetylated proteome profiles for postmenopausal women and premenopausal women, 151 types of proteins were found upregulated and 65 were downregulated, along with 23 acetylated sites upregulated and 220 sites downregulated. For Immune response, the complement and coagulation cascades plus the citrate cycle and cellular detoxification were found to be significantly enhanced, while the extracellular structure and matrix organization, ECM-receptor interactions plus the infections were markedly suppressed. In addition, the amino acids around the acetylated sites were enriched by motif analysis, which can help us uncover amino acid sequence and search for the specific target in the subsequent study.

Conclusion

Global and acetylated proteome Profiles in ovary differ between the premenopausal and postmenopausal groups. These proteomic-level changes may offer some potential biological markers to identify the pathological changes in ovary and help relieve and treat the associated signs and symptoms, and ultimately improve women’s health care.
  相似文献   

8.
Behavioral laterality is widely found among vertebrates, but has been little studied in aquatic invertebrates. We examined behavioral laterality in attacks on prey shrimp by the cuttlefish, Sepia lycidas, and correlated this to their morphological asymmetry. Behavioral tests in the laboratory revealed significant individual bias for turning either clockwise or counterclockwise toward prey, suggesting behavioral dimorphism in foraging behavior. Morphological bias was examined by measuring the curvature of the cuttlebone; in some the cuttlebone was convex to the right (righty), while in others, the cuttlebone was convex to the left (lefty). The frequency distributions of an index of cuttlebone asymmetry were bimodal, indicating that populations were composed of two types of individuals: "righty" and "lefty." Moreover, an individual's laterality in foraging behavior corresponded with the asymmetry of its cuttlebone, with righty individuals tending to turn counterclockwise and lefty ones in the opposite direction. These results indicate that cuttlefish exhibit behavioral dimorphism and morphological antisymmetry in natural populations. The presence of two types of lateral morph in cuttlefish provides new information on the relationship between antisymmetric morphologies and the evolution of individual laterality in behavioral responses in cephalopods. The implications of these findings for the interpretation of ecological meaning and maintenance mechanisms of laterality in cuttlefish are also discussed.  相似文献   

9.
An approach to the estimation of the lateral phenotype in children has been developed. During the study, more than 20 lateral phenotypes were identified in six-to seven-year-old children. The most frequent are the following lateral phenotypes: dextrality (motor and sensory), motor dextrality and sensory sinistrality, and motor dextrality and sensory ambidexterity (with a dominant left ear and right eye and with a dominant right ear and left eye). Unilateral left-handers accounted for 0.1% of all children studied; thus, the use of the laterality profile of motor functions as a “marker” of the brain functional asymmetry is rather questionable.  相似文献   

10.

Background

Factors determining patterns of laterality manifestation in mammals remain unclear. In primates, the upright posture favours the expression of manual laterality across species, but may have little influence within a species. Whether the bipedalism acts the same in non-primate mammals is unknown. Our recent findings in bipedal and quadrupedal marsupials suggested that differences in laterality pattern, as well as emergence of manual specialization in evolution might depend on species-specific body posture. Here, we evaluated the hypothesis that the postural characteristics are the key variable shaping the manual laterality expression across mammalian species.

Methodology/Principal Findings

We studied forelimb preferences in a most bipedal marsupial, brush-tailed bettong, Bettongia penicillata in four different types of unimanual behavior. The significant left-forelimb preference at the group level was found in all behaviours studied. In unimanual feeding on non-living food, catching live prey and nest-material collecting, all or most subjects were lateralized, and among lateralized bettongs a significant majority displayed left-forelimb bias. Only in unimanual supporting of the body in the tripedal stance the distribution of lateralized and non-lateralized individuals did not differ from chance. Individual preferences were consistent across all types of behaviour. The direction or the strength of forelimb preferences were not affected by the animals’ sex.

Conclusions/Significance

Our findings support the hypothesis that the expression of manual laterality depends on the species-typical postural habit. The interspecies comparison illustrates that in marsupials the increase of bipedality corresponds with the increase of the degree of group-level forelimb preference in a species. Thus, bipedalism can predict pronounced manual laterality at both intra- and interspecific levels in mammals. We also conclude that quadrupedal position in biped species can slightly hinder the expression of manual laterality, but the evoked biped position in quadrupedal species does not necessarily lead to the enhanced manifestation of manual laterality.  相似文献   

11.
The mesencephalic dopamine (DA) system is the main DA system related to affective and cognitive functions. The system consists of two different cell groups, A9 and A10, which originate from different regions of the midbrain. The striatum is the main input from the midbrain, and is functionally organized into associative, sensorimotor and limbic subdivisions. At present, there have been few studies investigating the associations of DA functions between striatal subdivisions and extrastriatal regions. The aim of this study was to investigate the relationship of DA D1 receptor (D1R) expression between striatal subdivisions and extrastriatal regions in humans using positron emission tomography (PET) with voxel-by-voxel whole brain analysis. The PET study was performed on 30 healthy subjects using [11C]SCH23390 to measure D1R expression. Parametric images of binding potentials (BP ND) were created using the simplified reference tissue model. Regions of interest were defined for striatal subdivisions. Multiple regression analysis was undertaken to determine extrastriatal regions that were associated with each striatal subdivision in BP ND using statistical parametric mapping 5. The BP ND values of associative, sensorimotor and limbic subdivisions were similarly correlated with those of multiple brain regions. Regarding the interrelationships among striatal subdivisions, mutual correlations were found among associative, sensorimotor and limbic subdivisions in BP ND as well. The relationships in BP ND between striatal subdivisions and extra-striatal regions suggest that differential striatal subdivisions and extrastriatal regions have a similar biological basis of D1R expression. Different DA projections from the midbrain did not explain the associations between striatal subdivisions and extrastriatal regions in D1R expression, and the DA-related neural networks among the midbrain, striatum and the other regions would contribute to a similar D1R expression pattern throughout the whole brain.  相似文献   

12.

Objectives

While various clinical and pharmacological determinants for chemotherapy-associated cognitive impairment have been identified, conflicting evidence suggests that cytokines might play an intermediary role. The objective of this systematic review was to evaluate the current evidence pertaining to the associations among chemotherapy, cytokines induction and cognitive impairment in cancer patients.

Methods

A literature search with PubMed and SciVerse Scopus was conducted in March 2013 to gather relevant articles and abstracts that fulfilled the inclusion and exclusion criteria. This review included studies that had performed objective and/or subjective cognitive assessments and cytokine measurements on defined populations of cancer patients who received chemotherapy.

Results

High methodological heterogeneity existed among the selected studies which differed in cancer populations, subject characteristics, cognitive endpoints, types of cytokines tested and their measurement methods. Weak to moderate correlations were observed between IL-1β, IL-6, TNF-α levels, and different degrees of cognitive impairment. Different types of chemotherapy treatments might lead to varying presentations and severities of cytokine-induced cognitive impairment. Notably, the time concordance between the onset of cytokine induction and occurrence of cognitive impairment was not well elucidated. A number of confounding factors was identified to interfere with the expression levels of cytokines; these confounders included subjects'' cancer types, ages, genders, genetics and psychosocial characteristics such as anxiety, depression and fatigue.

Conclusion

Although existing studies observed cognitive impairment and cytokine dysregulation in patients who receive chemotherapy, our results suggest that the intermediary role of cytokines in post-chemotherapy cognitive impairment is still controversial and requires further evaluation. A list of methodological recommendations is proposed to harmonize future studies of this subject matter.  相似文献   

13.

Background

Reactive oral fluid and whole blood rapid HIV tests must be followed with a confirmatory test (Western blot (WB), immunofluorescent assay (IFA) or approved nucleic acid amplification test (NAAT)). When the confirmatory result is negative or indeterminate (i.e. discordant with rapid result), repeat confirmatory testing should be conducted using a follow-up specimen. Previous reports have not described whether repeat testing adequately resolves the HIV-infection status of persons with discordant results.

Methodology

Post-marketing surveillance was conducted in 368 testing sites affiliated with 14 state and 2 city health departments from August 11, 2004 to June 30, 2005 and one health department through December 31, 2005. For persons with discordant results, data were collected on demographics, risk behaviors, HIV test results and specimen types. Persons with repeat confirmatory results were classified as HIV-infected or uninfected. Regression models were created to assess risk factors for not having repeat testing.

Principal Findings

Of 167,371 rapid tests conducted, 2589 (1.6%) were reactive: of these, 2417 (93%) had positive WB/IFA, 172 (7%) had negative or indeterminate WB/IFA. Of 89/172 (52%) persons with a repeat confirmatory test: 17 (19%) were HIV-infected, including 3 with indeterminate WB and positive NAAT; 72 (81%) were uninfected, including 12 with repeat indeterminate WB. Factors associated with HIV-infection included having an initial indeterminate WB/IFA (vs. negative) (p<0.001) and having an initial oral fluid WB (vs. serum) (p<0.001). Persons who had male-female sex (vs. male-male sex) were at increased risk for not having a repeat test [adjusted OR 2.6, 95% CI (1.3, 4.9)].

Conclusions

Though only half of persons with discordant results had repeat confirmatory testing, of those who did, nearly one in five were HIV-infected. These findings underscore the need for rapid HIV testing programs to increase repeat confirmatory testing for persons with discordant results. Because of the lower sensitivity of oral fluid WBs, confirmatory testing following a reactive rapid test should be conducted using serum or plasma, when possible.  相似文献   

14.
The initial stage of the escape response (C-bend of the body) upon sudden impact of electric current on free-swimming fish was studied in young roach (Rutilus rutilus). More than half of the fish showed distinct behavioral laterality, i.e., a stabile tendency to bend either to the left or to the right, and retained it until the next test conducted 10 days later. The majority of fish bent to the left, but the difference between the proportions of individuals that showed opposite lateralities lacked statistical significance. This response and the type of laterality are stable and simple to record, which makes the C-bend a convenient experimental model for studying behavioral asymmetry in fishes.  相似文献   

15.

Objective

We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values.

Materials and Methods

In 2003–2005 cognitive function was assessed in a cohort of 18–27 year old offspring of women with diet-treated gestational diabetes mellitus (n = 153) and offspring from the background population (n = 118). The main outcome measure was global cognitive score derived from Raven’s Progressive Matrices and three verbal subtests from the Weschler Adult Intelligence Scale. Maternal fasting- and 2-hour blood glucose values from the diagnostic oral glucose tolerance test were used as exposure variables.

Results

Offspring of women with gestational diabetes mellitus had a lower global cognitive score, than offspring from the background population (93.1 vs. 100.0, P<0.001). However, when adjusted for maternal age at delivery, parity, smoking during pregnancy, pre-pregnancy overweight, family social class, parental educational level, gender, birth weight, gestational age, perinatal complications and offspring age at follow-up, the difference was no longer statistically significant. Offspring global cognitive score decreased significantly with increasing maternal fasting glucose (β = −4.5, 95% CI −8.0 to −0.9, P = 0.01) and 2-hour glucose (β = −1.5, −2.9 to −0.2, P = 0.03) in univariate general linear models, but not when adjusted for family social class and parental educational level.

Conclusions

Lower cognitive test scores in adult offspring of women with diet-treated gestational diabetes were explained by well known predictors of cognitive function, but not by maternal hyperglycaemia during pregnancy. We find it reassuring that mild intrauterine hyperglycaemia does not seem to have adverse effect on offspring cognitive function.  相似文献   

16.
Cerebral lateralization is a widespread trait among animals, is often manifested as side biases in behaviour (laterality) and has been suggested to provide fitness benefits. Here we examined the influence of laterality on the organisation of fish schools using rainbowfish (Melanotaenia spp) as model species. The pattern and strength of laterality for each individual was determined by examining eye preferences whilst examining their reflection in a mirror. Schools of four fish of known laterality were then created and the preferred position for each fish within the school was repeatedly observed in a flume. Fish which showed right eye preferences in the mirror test preferentially adopted a position on the left side of the school. Conversely, fish that showed left eye preferences in the mirror test or where non-lateralised preferentially adopted a position slightly to the right side of the school. However, this general pattern varied depending on the species and sex of the school. Our results strongly implicate individual laterality in the geometry of school formation.  相似文献   

17.

Objective

Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others).

Design

To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008.

Methods

Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status.

Results

HIV prevalence was 0.06% among 921,438 pregnant women and 1.34% among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14% vs. 0.21%, odds ratio 0.65 [95% confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p<0.01) to have Western blot-negative (52.9% vs. 9.8%) and indeterminate results (17.0% vs. 3.7%) and lower PPV (30% vs. 87%). The p24 band was detected more often among pregnant women (p<0.01).

Conclusions

False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others. Pregnant women with reactive EIAs were more likely to have negative and indeterminate Western blot results due to lower HIV prevalence and higher p24 reactivity, respectively. Indeterminate results may complicate clinical management during pregnancy. Alternative methods are needed to rule out infection in persons with reactive EIAs from low prevalence populations.  相似文献   

18.

[Purpose]

The purpose of this study was to investigate the effects of aquatic exercise and CES treatment on the cognitive function by using K-WAB and BDNF, IGF-1, and VEGF of persons with intellectual disabilities.

[Methods]

All subjects were 15 male with intellectual disabilities who were participating in the aquatic training program and CES treatment during 12 weeks at rehabilitation center. The subjects were divided into control group, exercise group, and exercise+CES group. Blood samples for BDNF, IGF-1, and VEGF were taken from brachial vein at rest between before and after treatment.

[Results]

The results are summarized as follows: Cognitive function level increased significantly in the exercise+CES group compared to those in the exercise and control group. The changes of blood IGF-1 concentration were no significant difference among groups. The changes of blood BDNF and VEGF concentration were significantly increased in exercise group and exercise+CES group than control group. However, blood BDNF and VEGF concentration were significantly difference between exercise group and exercise+CES group.

[Conclusion]

In conclusion, it can be concluded that CES treatment with exercise can amend cognitive function of persons with intellectual disabilities more effectively and increase of BDNF and VEGF by exercise can explain the cognitive function improvement of persons with intellectual disabilities.  相似文献   

19.

Background

Breast cancer is a heterogenous disease that impacts racial/ethnic groups differently. Differences in genetic composition, lifestyles, reproductive factors, or environmental exposures may contribute to the differential presentation of breast cancer among Hispanic women.

Materials and Methods

A population-based study was conducted in the city of Santiago de Compostela, Spain. A total of 645 women diagnosed with operable invasive breast cancer between 1992 and 2005 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics of the tumors were collected. Hormone receptor negative tumors were compared with hormone receptor postive tumors on their clinico-pathological characteristics as well as risk factor profiles.

Results

Among the 645 breast cancer patients, 78% were estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+), and 22% were ER−&PR−. Women with a family history of breast cancer were more likely to have ER−&PR− tumors than women without a family history (Odds ratio, 1.43; 95% confidence interval, 0.91–2.26). This association was limited to cancers diagnosed before age 50 (Odds ratio, 2.79; 95% confidence interval, 1.34–5.81).

Conclusions

An increased proportion of ER−&PR− breast cancer was observed among younger Spanish women with a family history of the disease.  相似文献   

20.

Objectives

While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables.

Methods

A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E ε4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification.

Results

The best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were “low-risk” and 38% “high-risk”. Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029). Women with a college degree or above were more likely to be in the low-risk class (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012; respectively). The prevalence rate of APOE-ε4 was higher in the high-risk class compared with rates in the low-risk class.

Conclusion

Among recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to phenotypes for CV disease risk. Evaluating the evolution of phenotypes could in turn clarify preclinical disease, and screening and preventive strategies.ClinicalTrials.gov NCT00154180  相似文献   

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