Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial.

OBJECTIVE: To determine the cognitive effects of long-term dietary soy isoflavones in a daily dose comparable to that of traditional Asian diets. METHODS: In the double-blind Women's Isoflavone Soy Health trial, healthy postmenopausal women were randomly allocated to receive daily 25 g of isoflavone-rich soy protein (91 mg of aglycone weight of isoflavones: 52 mg of genistein, 36 mg of daidzein, and 3 mg glycitein) or milk protein-matched placebo. The primary cognitive endpoint compared between groups at 2.5 years was change from baseline on global cognition, a composite of the weighted sum of 14 neuropsychological test score changes. Secondary outcomes compared changes in cognitive factors and individual tests. RESULTS: A total of 350 healthy postmenopausal women aged 45-92 years enrolled in this trial; 313 women with baseline and endpoint cognitive test data were included in intention-to-treat analyses. Adherence in both groups was nearly 90%. There was no significant between-group difference on change from baseline in global cognition (mean standardized improvement of 0.42 in the isoflavone group and 0.31 in the placebo group; mean standardized difference 0.11, 95% confidence interval [CI] -0.13 to 0.35). Secondary analyses indicated greater improvement on a visual memory factor in the isoflavone group (mean standardized difference 0.33, 95% CI 0.06-0.60) but no significant between-group differences on 3 other cognitive factors or individual test scores, and no significant difference within a subgroup of younger postmenopausal women. CONCLUSION: For healthy postmenopausal women, long-term dietary soy isoflavone supplementation in a dose comparable to that of traditional Asian diets has no effect on global cognition but may improve visual memory. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that long-term dietary supplementation with isoflavone-rich soy protein does not improve global cognition of healthy postmenopausal women.

Effects of sex-sorting and sperm dosage on conception rates of Holstein heifers: is comparable fertility of sex-sorted and conventional semen plausible?

The conception rates of Holstein heifers after AI with 2.1 or 10 × 10(6) sperm dosages of sex-sorted or conventionally processed sperm were compared. Ejaculates collected by artificial vagina from 8 Holstein sires were cryopreserved at either 2.1 or 10 × 10(6) sperm per dose with or without sorting to 90% purity for X-chromosome-bearing spermatozoa using flow cytometry. All treatments were processed in an egg-yolk (20%), TRIS, glycerol (7%) extender and packaged in color-coded 0.25-mL French straws. Straws (n=350 straws/treatment per sire) were packaged and distributed in aliquots of 12 (3 straws of each treatment) to 51 herds of Holstein heifers. Straw color was recorded in the on-farm record keeping system at the time of AI and retrieved by electronic download. In total, 9,172 services were recovered, providing a mean sample size of 287±3.5 services/sperm dose per semen type within sire (range: 248 to 318). Conception rates were influenced by the main effects of herd, sire, semen type, sperm dosage, and service number. The herd by sperm dosage interaction was the only interaction determined to be significant and implies that some herds (technicians) are more proficient than others at maintaining high levels of conception with decreased sperm dosages. Across herds and sires, the conception rates of each semen type by sperm dosage combination were as follows: 2.1 × 10(6) sex-sorted, 38%, n=2,319; 10 × 10(6) sex-sorted, 44%, n=2,279; 2.1 × 10(6) conventional, 55%, n=2,282; and 10 × 10(6) conventional, 60%, n=2,292. The observation that conception rates of sex-sorted semen were improved by the 10 × 10(6) sperm dosage is encouraging toward the prospectus of development of a commercially available sex-sorted product with improved conception potential over existing technology. However, the failure of the 10 × 10(6) sex-sorted sperm dosage to achieve conception rates comparable to either dosage of conventional semen is somewhat discouraging toward the plausibility of comparable conception rates to conventional semen in the absence of major technological advances in efficiency of sperm sorting or cryopreservation.

Effects of 2.1 and 3.5x10(6) sex-sorted sperm dosages on conception rates of Holstein cows and heifers.

The objective was to compare conceptions rates of Holstein cows and heifers after artificial insemination (AI) with 2.1 or 3.5x10(6) sex-sorted sperm or 15x10(6) conventional sperm. Ejaculates collected from 7 Holstein sires were cryopreserved conventionally at 15x10(6) sperm per dose or sorted to 90% purity for X-chromosome-bearing spermatozoa using flow cytometry and cryopreserved at either 2.1 or 3.5x10(6) sperm per dose. All treatments were processed in an egg-yolk (20%), Tris, glycerol (7%) extender and packaged in color-coded 0.25-mL French straws. Straws (n=700 straws/dosage per sire) were packaged and distributed in aliquots of 12 (4 straws/sperm dosage) to 69 Holstein herds with an across-herd goal of achieving approximately 50% use in heifers and cows. Straw color was recorded in the on-farm recordkeeping system at the time of AI and retrieved by electronic download. Data for cows and heifers were analyzed separately. Among heifers, 6,268 services were retrieved from 45 herds (298+/-4.2 services/sperm dose per sire; range: 244 to 344). Conception rate of heifers was influenced by the sire by treatment interaction. Conception rate of the 2.1 and 3.5x10(6) sex-sorted sperm dosages were comparable in 6 of 7 sires. Conception rate of both sex-sorted dosages were less than those of conventional semen for 6 of 7 sires. Across sires, heifer conception rates for 2.1 and 3.5x10(6) sex-sorted sperm dosages and 15x10(6) conventional dosages were 44, 46, and 61%, respectively. Among cows, 5,466 services were retrieved from 52 herds (260+/-3.3 services/sperm dose per sire; range: 236 to 289). Conception rates of cows were influenced by herd, sire, and sperm dosage. Conception rates of the 2.1 and 3.5x10(6) sex-sorted sperm dosage were comparable for all 7 sires. Conception rates of 2.1x10(6) sex-sorted sperm dosage were less than those of conventional semen for 4 of 7 sires and conception rates of the 3.5x10(6) sex-sorted sperm dosage were less than those of conventional semen for 2 of 7 sires. Across sires, conception rates for 2.1 and 3.5x10(6) sex-sorted sperm dosages and 15x10(6) conventional dosages in cows were 23, 25, and 32%, respectively. In conclusion, these data could not confirm that a meaningful improvement in conception rates should be expected in cows or heifers from increasing sex-sorted sperm dosage from 2.1 to 3.5x10(6) sperm per dose.

Effect of sex-sorted sperm dosage on conception rates in Holstein heifers and lactating cows.

Ejaculates were collected by artificial vagina from 3 Holstein sires and sorted to 90% purity for X-chromosome-bearing spermatozoa (range 88 to 93%) using flow cytometry. Sorted sperm were diluted to 2.1, 3.5, or 5.0 x 10(6) sperm per dose in an egg yolk (20%), Tris, glycerol (7%) extender. Collections were repeated until >600 straws per sperm dose per sire were obtained. Each sperm dose was loaded into color-coded 0.25-mL French straws, with alternate colors used to define treatments across sires. Within sires, straws were packaged at 9 per cane (3 of each color) and strategically allocated to 75 Holstein herds with targets for 50% use in heifers and 50% in lactating cows. Straw color was recorded in the on-farm record-keeping system at the time of insemination. Data were analyzed separately for cows and heifers. Among heifers, a total of 2,125 usable records were retrieved from 51 herds (238 +/- 5.5 services/ sperm dose per sire, range: 218 to 263). Conception rates in heifers were influenced by the sire x sperm dosage interaction. Within sire A, conception rates of heifers were greater for the 5 x 10(6) (59.5%) than for the 2.1 x 10(6) (46.4%) sperm dose and intermediate for the 3.5 x 10(6) sperm dose (52.2%). However, across sires, sperm dosage had no effect on heifer conception rates (46.7, 51.2, and 52.5% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). Among cows, a total of 2,369 services were retrieved from 56 herds (263 +/- 8.8 services/sperm dose per sire, range: 233 to 303). Conception rates of cows (29.4%) were not affected by sire or sperm dosage (27.0, 29.1, and 30.3% for the 2.1, 3.5, and 5.0 x 10(6) sperm dosages, respectively). In conclusion, these data indicate that an increased sperm dosage may enhance virgin heifer conception rates for some (but not all) sires, whereas neither sire nor sexed-sperm dosage affected conception rates of lactating cows. Additional studies of sexed-sperm dosage across a larger sampling of bulls are warranted to determine whether and how such a practice can be implemented cost effectively for the benefit of the dairy industry.

Anosognosia and Alzheimer's disease: the role of depressive symptoms in mediating impaired insight.

The relation between anosognosia and dementia severity in Alzheimer's disease (AD) has been unclear. We constructed a measure that quantified the difference between the perceptions of deficits of patients with AD (n = 23) and ratings from a knowledgeable informant as a measure of anosognosia. There was no correlation between dementia severity and anosognosia. However, dementia severity was positively correlated with the degree of anosognosia after controlling for depressive symptomatology (p =.03). Post-hoc analyses, also controlling for depressive symptoms, indicated that higher levels of anosognosia were associated with lower performance on specific cognitive tasks. These results suggest depressive symptoms may confound the relationship between anosognosia and dementia severity.

Associations between circulating sex steroid hormones and cognition in normal elderly women.

OBJECTIVE: To provide exploratory analyses of associations between levels of several sex hormones and cognitive performance in elderly women. BACKGROUND: Sex steroid hormones are implicated in the cognitive processes of the adult brain. Comparing cognitive performance across or between conditions associated with different hormone levels, such as phases of the menstrual cycle, surgical menopause, and estrogen replacement therapy suggests conditions with higher levels of estrogen are associated with better verbal memory and possibly worse visuospatial ability. METHOD: The authors measured circulating sex hormone levels in 39 highly educated, nondemented, predominantly white elderly women. Levels were correlated with neuropsychological performance, controlling for age, education, frequency of prior testing, use of estrogen replacement, and depression. RESULTS: High estradiol levels were associated with better delayed verbal memory and retrieval efficiency, whereas low levels were associated with better immediate and delayed visual memory. Levels of testosterone were related positively to verbal fluency. Levels of progesterone and androstenedione were unrelated to cognitive performance. CONCLUSIONS: Both estrogen and testosterone showed associations with cognitive performance. Estrogen may enhance, and depress, specific cognitive skills.

Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial.

BACKGROUND: AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. METHODS: Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. RESULTS: Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer's Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. CONCLUSION: Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.

Lifelong estrogen exposure and cognitive performance in elderly women.

Fluctuating endogenous and exogenous estrogens influence cognition in women. In this study, cognitive functioning in elderly women was examined by applying methodology used in understanding the effects of chronic estrogen exposure on hormone-sensitive tissue other than the brain. An index, combining menstrual, reproductive, and physical markers associated with estrogen levels, was developed for elderly, nondemented, predominantly Caucasian women (n = 87). This index related to better performance on two verbal factors, one attentional and one global in nature. Findings suggest that estrogen exposure across the life span plays a role in brain aging. Possible physiological mechanisms for this effect are discussed.

Pregnancy, the postpartum, and steroid hormones: effects on cognition and mood.

The effects of pregnancy on cognition and mood were examined using a repeated-measures design. Nineteen women, average age 33, were tested with a comprehensive neuropsychological battery during their last 2 months of pregnancy and again within 2 months of delivery. Blood samples were obtained from all subjects and assayed for a variety of steroid hormones implicated in cognitive and mood functioning. Most participants also completed several self-report measures of mood. In comparison with performance after delivery, women showed significantly more impairment in aspects of verbal memory during pregnancy and also tended to report more negative mood states. Memory deficits were not explained by mood disturbances. No hormone assayed consistently related to cognitive performance during pregnancy. During pregnancy, higher levels of progesterone (P) were associated with greater mood disturbances and higher levels of dehydroepiandrosterone (DHEA) with better mood. After delivery, testosterone (T) was strongly and consistently associated with greater reported mood disturbances. Our results confirm a peripartal memory deficit, which cannot be explained by the dramatic rise in circulating steroid hormones, or by mood status during pregnancy. Steroidal hormones, namely P, DHEA and T, appear to play a role in mood disturbances during, and after, pregnancy. Studies beginning earlier in pregnancy and continuing for an extended period of time after delivery are needed to confirm and expand these observations.

Depression after traumatic brain injury as a function of Glasgow Outcome Score.

One hundred and five patients with traumatic brain injury (TBI) were assessed for depressive symptomatology at 6 months postinjury and 66 of those patients were examined again at 12 months postinjury. At 6 months, 42% of the patients with TBI and 20% of the Other Injury Control Group (OIC) were identified as depressed. Individuals with poor outcome (as measured by Glasgow Outcome Score [GOS]) had a higher frequency of depressive symptomatology than those with good GOS outcome. At 12 months, 36% of the patients with TBI and 28% of the OIC group were identified as depressed. At 12 months, there was no difference in terms of frequency of depressive symptomatology among patients with TBI with poor, moderate, or good outcome.

Depression, cognition, and functional correlates of recovery outcome after traumatic brain injury.

The present study investigated the prevalence and magnitude of depressive symptomatology in a sample of patients who had sustained traumatic brain injury (TBI) six months earlier. Depression was examined as a function of recovery outcome status, and its association with neuropsychological functioning, personal competency, and employability was also explored. Subjects were 100 patients who had previously sustained moderate-to-severe TBI who were enrolled as research subjects in the UCLA Brain Injury Research Center, and 30 matched control subjects who had sustained traumatic injuries other than to the head six months prior to evaluation. The results showed a significant association between depression and recovery status as measured by the Glasgow Outcome Scale (GOS). A significant majority of depressed subjects were found in the poorer GOS outcome groups (severe and moderate disability), compared to TBI subjects who had good GOS outcomes, and control subjects. This association was also reflected in the magnitude of the mean depression scores on two self-report measures of depression. However, no association was found between depression status and performance on the neuropsychological measures. Effects of depression were found only on an examiner-rated Patient Competency scale, and a metacognition measure based on self-report. These results are discussed in terms of brain injury severity, recovery status, and metacognition issues in TBI and other disorders.

Neuropsychological, psychosocial and vocational correlates of the Glasgow Outcome Scale at 6 months post-injury: a study of moderate to severe traumatic brain injury patients.

Traumatic brain injury (TBI) subjects at Glasgow Outcome Scale levels 3 (severe disability), 4 (moderate disability), 5 (good recovery), and an other-injury control group (OIC) were compared in terms of neuropsychological, psychosocial, and vocational functioning 6 months after injury. Subjects were a sample of 100 patients with a moderate to severe traumatic brain injury (TBI) and a matched sample of 30 other-injury control subjects (OIC) enrolled in the UCLA Brain Injury Research Center study of TBI outcome. Overall, the results showed a systematic decrease in mean neuropsychological test performance as a function of increasing GOS severity, as well as an increased prevalence of symptoms of depression and lower ratings on measures assessing employability and capacity for self care. TBI patients in the 'severe' and 'moderate disability' groups were distinctly inferior to the 'good recovery' and 'OIC' groups, who were quite similar to each other in terms of cognitive, psychosocial, and vocational outcomes. The results demonstrate overall support for the predictive and concurrent validity of the GOS 6 months post injury. Despite these results, which strengthen the utility and appeal of the GOS for multicentre studies, concerns still remain regarding GOS category 4 (moderate disability), which was shown to lack sufficient discriminability in this study.

Mild closed-head injury in children and adolescents: behavior problems and academic outcomes.

The issue of whether mild head injuries (HIs) in children cause behavior problems and poor scholastic performance is controversial. This study included 119 children (range = 8-16 years old) with HI, 114 with other injuries, and 106 with no injury (NI). Behavioral functioning was assessed with the Child Behavior Checklist; academic functioning, with school grades and standardized testing. Higher T scores were found for both injury groups versus NI participants on preinjury behavioral status. All 3 groups' behavioral scores decreased relative to baseline at 1 year. HI and NI groups did not differ in school grades or achievement testing either pre- or postinjury. These results are consistent with the conclusion that head injury of the mildest type does not increase the probability of new overt behavioral or academic problems.

Mild head injury in children and adolescents: a review of studies (1970-1995).

In this article, the authors provide a comprehensive review of the research of mild head injury in children and adolescents from 1970 to 1995. Because of marked variability in methodologies across studies, a preliminary box-score tally was computed, without regard to studies' scientific or methodological merit. These results revealed 13 adverse, 18 null, and 9 indeterminate findings related to neuropsychological, academic, or psychosocial outcome. When studies were classified based on methodological merit, the stronger studies were generally associated with null outcomes across domains. However, a few of the less stronger neuropsychological studies (5 of 40) reported subthreshold and transitory alterations during the early postinjury period. At the present time, cautious acceptance of the null hypothesis is recommended until more definitive studies are conducted that address the problems raised in this review.

The semantic organization and classification of fourteen words by aphasic patients.

The purpose of this study was to assess both conceptual knowledge and classification skills in nonfluent and fluent aphasia by focusing on the aphasics' appreciation of class and function relations. The results illustrated that fluent and nonfluent aphasics appreciated both class and function relations. However, further study revealed that even though the fluent aphasic may know the function of an item, he is impaired in his ability to use this information. The nonfluent aphasics also illustrated this tendency not to use their knowledge about function, but to a lesser extent and without the consistency found in the performance of fluent aphasics.

Superoxide ion as a primary reductant in ascorbate-mediated ferritin iron release.

The mechanism of ascorbate-promoted ferritin iron reduction under aerobic conditions was studied. The initial rate of ferritin iron release was determined by spectrophotometric measurement of the Fe(ferrozine)3(2+) complex which absorbs at 562 nm. Variation of the initial ferrozine concentration had no influence on the rate of iron release suggesting that ferrozine does not participate in the rate-determining step. Experimental measurements of the initial rate of iron release as a function of ascorbate concentration resulted in saturation kinetics with Vmax = 2.0 X 10(-7) M.min-1 and KM = 1.3 X 10(-3) M. The effect of pH was quite pronounced with a maximal rate of iron release at pH 7.0. Stoichiometric measurements on the reaction mixture, with added catalase, resulted in a ratio of 2 Fe(II) released per ascorbate. Ascorbate-mediated iron release was inhibited 85% by superoxide dismutase, but 0% inhibition was noted with aposuperoxide dismutase. It is proposed that superoxide ion, generated during the iron-promoted oxidation of ascorbate, acts as a reductant of ferritin iron. A mechanism of ferritin iron release consistent with these experimental observations is discussed.

Semantic classification in aphasia: a study of basic, superordinate, and function relations.

Nonfluent and fluent aphasics were given classification tasks that required the aphasics to identify three kinds of relations: same basic level category, same superordinate level category, and same function. The subjects received the items in word and picture form. In addition the aphasics were required to name the items they were asked to classify. The results showed that the ability to classify is more disrupted in fluent aphasia than in nonfluent aphasia. Within fluent aphasia, the degree to which classification is disrupted is dependent upon the type of relation being tested. While the overall performance of the fluent aphasics was depressed in comparison to nonfluent aphasics, it was significantly more depressed on function relations. The ability to name an item had a significant effect on the ability to classify only for basic level items.

Profiles of right hemisphere language and speech following brain bisection.

A variety of language tasks were administered to two patients who had undergone staged callosal section in an effort to control otherwise intractable epilepsy. Right hemisphere lexical capacity varied and preliminary results suggest that the case displaying greater semantic power also possessed some syntactic competence. This same case (V.P.) was also capable of expressive language from the right hemisphere. This rare capacity allowed for fresh observations on the dynamic interactions of conscious control that occur in this kind of patient.

Structural analysis of colanic acid from Escherichia coli by using methylation and base-catalysed fragmentation. Comparison with polysaccharides from other bacterial sources.

Essentially the same methanolysis products were obtained after methylation of the slime and capsular polysaccharides from Escherichia coli K12 (S53 and S53C sub-strains) and the slime polysaccharides from E. coli K12 (S61), Aerobacter cloacae N.C.T.C. 5290 and Salmonella typhimurium SL1543. These were the methyl glycosides of 2-O-methyl-l-fucose, 2,3-di-O-methyl-l-fucose, 2,3-di-O-methyl-d-glucuronic acid methyl ester, 2,4,6-tri-O-methyl-d-glucose, 2,4,6-tri-O-methyl-d-galactose and the pyruvic acid ketal, 4,6-O-(1'-methoxycarbonylethylidene)-2,3-O-methyl-d-galactose. All were identified as crystalline derivatives from an E. coli polysaccharide. The structure of the ketal was proved by proton-magnetic-resonance and mass spectrometry, and by cleavage to pyruvic acid and 2,3-di-O-methyl-d-galactose. All these polysaccharides are therefore regarded as variants on the same fundamental structure for which the name colanic acid is adopted. Although containing the same sugar residues, quite different methanolysis products were obtained after methylation of the extracellular polysaccharide from Klebsiella aerogenes (1.2 strain). The hydroxypropyl ester of E. coli polysaccharide, when treated with base under anhydrous conditions, underwent beta-elimination at the uronate residues with release of a 4,6-O-(1'-alkoxycarbonylethylidene)-d-galactose. Together with the identification of 3-O-(d-glucopyranosyluronic acid)-d-galactose as a partial hydrolysis product, this establishes the nature of most, if not all, of the side chains as O-[4,6-O-(1'-carboxyethylidene)-d-galactopyranosyl]-(1-->4)-O-(d-glucopyranosyluronic acid)-(1-->3)-d-galactopyranosyl...