Interclinician agreement on the recognition of selected respiratory clinical signs in dogs and cats with abnormal breathing patterns.

In humans, classification of abnormal breathing patterns (ABP) and recognition of ancillary respiratory signs are difficult, as reflected by poor-to-moderate interclinician agreement. The aims of this study were to assess interclinician agreement for respiratory sign recognition in dogs and cats and evaluate the influence of clinical experience on agreement. Dogs and cats with ABP were recruited from three hospitals. Included animals were evaluated by three clinicians at each hospital before therapeutic intervention. Consensual definitions for each respiratory clinical sign were provided to all clinicians. Interclinician agreement was measured via Fleiss' kappa and intraclass correlation coefficient statistics. Influence of clinical experience on interobserver agreement was studied via mixed-effects logistic regression. One-hundred and fifteen dogs and 49 cats with ABP were recruited. Out of 12 clinical signs evaluated, only stertor (kappa, 0.80), stridor (kappa, 0.64), attenuation of heart/lung sounds (kappa, 0.60), and goose honking (kappa, 0.84) in dogs, and stertor (kappa, 0.65) and open-mouth breathing (kappa, 0.75) in cats, were considered sufficiently reliable among clinicians. Agreement on respiratory rate estimation was good in both species (intraclass correlation coefficient, 0.75). The greater the difference in clinical experience between two clinicians, the lower the odds of agreement between the two clinicians' respiratory physical examination findings. Interclinician agreement was demonstrated to be poor for recognition of most respiratory clinical signs in dogs and cats. Teaching and clinical experience acquisition should be encouraged to improve respiratory clinical sign recognition.

Association between respiratory clinical signs and respiratory localization in dogs and cats with abnormal breathing patterns.

The diagnostic values of respiratory signs have been under-investigated in pets. The study aim was to explore commonly assumed associations between respiratory signs and disease localization in pets with abnormal breathing patterns (ABP). Dogs and cats with ABP presenting to three hospitals were included if investigations permitted disease localization. Hypothesized associations between respiratory signs and disease location were evaluated via mixed-effects logistic regression. Sensitivity, specificity, and positive diagnostic likelihood ratio were calculated. One-hundred and fifteen dogs and 49 cats with ABP were recruited. Confirmed associations included: inspiratory effort with extra-thoracic airway disease (odds ratio [OR], 9.1; 95% confidence interval [95% CI] 3.0-27.2); expiratory effort with intra-thoracic airway disease (OR, 6.5; 95% CI, 2.3-18.1); paradoxical breathing and attenuation of heart/lung sounds with pleural space disease (paradoxical breathing: OR, 4.5; 95% CI 1.7-12.1; sound attenuation: OR, 11.5; 95% CI 4.0-33.3); decreased nasal airflow and stertor with nasal/pharyngeal disease (nasal airflow: OR, 26.2; 95% CI 8.1-84.8; stertor: OR, 155.2; 95% CI 24.9-968.8); stridor with laryngeal or tracheal disease (laryngeal disease: OR, 39.9; 95% CI 7.6-209.0; tracheal disease: OR, 32.4; 95% CI 4.2-248.0); tracheal sensitivity with bronchial disease (OR, 3.8; 95% CI 1.5-9.6); crackles with pulmonary or bronchial disease (pulmonary disease: OR, 5.4; 95% CI 2.1-13.8; bronchial disease: OR, 3.9; 95% CI 1.6-9.8); and goose honking with tracheal disease (all dogs with goose honking had tracheal involvement). Select respiratory signs provide guidance to localize and prioritize causes of the underlying respiratory disease in pets, allowing targeted interventions in animals with ABP.

Sex and Age Differences in the Association of Blood Pressure and Hypertension with Cognitive Function in the Elderly: The Rancho Bernardo Study.

OBJECTIVES: This study examines sex and age differences in associations of systolic and diastolic blood pressure (SBP, DBP), pulse pressure and hypertension with cognitive function in a community-dwelling population. DESIGN: Cross-sectional study. SETTING: Research clinic visit in 1988-91. PARTICIPANTS: Participants were 693 men and 1022 women aged 50-97 Measurements: Blood pressure was measured and 12 cognitive function tests were administered. RESULTS: Average age was 73.8±9.9 in men and 73.2±9.3 in women; 62.6% of men and 63.4% of women were hypertensive (SBP≥140 mmHg, DBP≥90 mmHg, or antihypertensive medication use). Each 5-unit increment in SBP, DBP, or pulse pressure and categorical hypertension was associated with significantly increased odds of poor verbal fluency performance in men and poor Trails B performance in women, with strongest associations for hypertension (OR=1.97, CI:1.01,3.85 in men; OR=1.51, CI:1.01,2.26 in women). After age stratification, associations remained statistically significant in younger (<80 years ) but not older (≥80 years) participants. CONCLUSION: Blood pressure as a continuous or categorical variable was associated with poor performance on cognitive function tests, but domains varied by sex and associations were found only in those younger than 80 years. The absent associations in those aged 80 years and older could support the hypothesis that increased blood flow is required to maintain cerebral perfusion with advancing age, or could reflect a survivor effect.

Association between Dietary Sodium Intake and Cognitive Function in Older Adults.

OBJECTIVE: To examine the association of dietary sodium intake with cognitive function in community-dwelling older adults. DESIGN: Cross-sectional study. SETTING: Southern California community. PARTICIPANTS: White men (n=373) and women (n=552), aged 50-96 years from the Rancho Bernardo Study, a longitudinal study of cardiovascular disease risk factors and healthy aging. MEASUREMENTS: During the 1992-1996 research clinic visit, a food frequency questionnaire was used to determine daily sodium intake; cognitive function was assessed with Trails Making Test, part B (Trails B), Mini-Mental State Exam (MMSE), and Verbal Fluency Test (VFT); and medical, clinical and demographic information was obtained. Linear regression was used to assess the association between calorie-adjusted sodium intake and cognitive test scores with adjustment for demographic, behavioral and health measures. Logistic regression examined the odds of having cognitive impairment by sodium intake. RESULTS: Lower sodium intake was associated with poorer performance on Trails B (p=0.008) and MMSE (p=0.003) after controlling for age, sex, and education. Associations did not differ by sex, but there was a significant interaction by age for the Trails B: older (≥80 years), but not younger, adults showed worse performance with lower sodium intake (p=0.03). Associations remained significant after additional adjustment for smoking, alcohol intake, exercise, body weight, cardiovascular risk factors, kidney function, diuretic medication use, and diet quality. Lower daily sodium intake was associated with increased odds of cognitive impairment on the MMSE (score < 26; OR per SD decrease = 1.12, 95% CI 1.08, 1.16). Concluson: Lower sodium intake was associated with worse cognitive function in older community-dwelling adults. For the maintenance of cognitive health, older adults may be advised to avoid very low sodium diets.

Moderate, Regular Alcohol Consumption is Associated with Higher Cognitive Function in Older Community-Dwelling Adults.

BACKGROUND: Evidence suggests that moderate alcohol consumption may protect against cognitive decline and dementia. However, uncertainty remains over the patterns of drinking that are most beneficial. OBJECTIVE: To examine associations between amount and frequency of alcohol consumption with multiple domains of cognitive function in a well-characterized cohort of older community-dwelling adults in southern California. DESIGN: Observational, cross-sectional cohort study. SETTING: A research visit between 1988-1992 in Rancho Bernardo, California. PARTICIPANTS: 1624 participants of the Rancho Bernardo Study (mean age ± SD = 73.2 ± 9.3 years). Measurements: Participants completed a neuropsychological test battery, self-administered questionnaires on alcohol consumption and lifestyle, and a clinical health evaluation. We classified participants according to average amount of alcohol intake into never, former, moderate, heavy and excessive drinkers, and according to frequency of alcohol intake, into non-drinkers, rare, infrequent, frequent and daily drinkers. We examined the association between alcohol intake and cognitive function, controlling for age, sex, education, exercise, smoking, waist-hip ratio, hypertension and self-assessed health. RESULTS: Amount and frequency of alcohol intake were significantly associated with cognitive function, even after controlling for potentially related health and lifestyle variables. Global and executive function showed positive linear associations with amount and frequency of alcohol intake, whereas visual memory showed an inverted U-shaped association with alcohol intake, with better performance for moderate and infrequent drinkers than for non-drinkers, excessive drinkers or daily drinkers. CONCLUSIONS: In several cognitive domains, moderate, regular alcohol intake was associated with better cognitive function relative to not drinking or drinking less frequently. This suggests that beneficial cognitive effects of alcohol intake may be achieved with low levels of drinking that are unlikely to be associated with adverse effects in an aging population.

Kyphosis and Sleep Characteristics in Older Persons: The Rancho Bernardo Study.

BACKGROUND: Kyphosis is a forward curvature of the thoracic spine that is associated with multiple adverse health outcomes. This cross-sectional study examined the association between kyphosis and sleep characteristics. METHODS: Participants were 468 white, community-dwelling individuals (women = 255; men = 213) from the Rancho Bernardo cohort who had kyphosis assessed using a flexicurve ruler at a 2007-09 follow-up research clinic visit and sleep quality assessed by mailed survey in 2010 with the Pittsburgh Sleep Quality Index (PSQI), scored 0-18, with >5 indicative of poor sleep quality. RESULTS: Women had a mean age of 73.3 ± 8.8 years; men 74.2 ± 8.1 years. Mean flexicurve measures were 12.6 ± 3.2 for women and 12.1 ± 2.6 for men. No significant associations were found between kyphosis and any self-reported sleep measure in men, but women with worse kyphosis had poorer sleep quality, based on total PSQI score and two PSQI subcomponents. In women, with each unit increase in kyphosis, after adjusting for age, marital status, height, general health, calcium supplement use, estrogen use, exercise, arthritis, and depression, there was an associated increase in total PSQI score, indicating worse sleep quality (standard ß-estimate = 1.37, 95% CI: 1.03, 1.82). Women with worse kyphosis were also more likely to sleep ≤ 7 hours (Odds Ratio (OR) = 1.11, 95% CI: 1.02, 1.22) and report use of sleep medications (OR = 1.14, 95% CI: 1.03, 1.25). CONCLUSIONS: In women only, those with worse flexicurve kyphosis had worse scores on the PSQI, slept fewer hours (≤ 7 hours) and were more likely to report sleep medication use than those with less kyphosis. The association between kyphosis and objective sleep measures in older persons deserves further investigation.

The risk of surgical site infection and re-admission in obese patients undergoing total joint replacement who lose weight before surgery and keep it off post-operatively.

This study evaluated whether obese patients who lost weight before their total joint replacement and kept it off post-operatively were at lower risk of surgical site infection (SSI) and re-admission compared with those who remained the same weight. We reviewed 444 patients who underwent a total hip replacement and 937 with a total knee replacement who lost weight pre-operatively and sustained their weight loss after surgery. After adjustments, patients who lost weight before a total hip replacement and kept it off post-operatively had a 3.77 (95% confidence interval (CI) 1.59 to 8.95) greater likelihood of deep SSIs and those who lost weight before a total knee replacement had a 1.63 (95% CI 1.16 to 2.28) greater likelihood of re-admission compared with the reference group. These findings raise questions about the safety of weight management before total replacement of the hip and knee joints.

The association of thyroid stimulating hormone levels with cognitive function and depressed mood: the Rancho Bernardo study.

OBJECTIVE: To evaluate the association of thyroid stimulating hormone levels with cognitive function and depressed mood in a community-based sample. DESIGN: Cross-sectional study. SETTING: Clinic visit in 1999- 2003. PARTICIPANTS: Community-dwelling men (N=447) and women (N=663) aged 42-99 years. MEASUREMENT: Cognitive function was assessed with the Buschke-Fuld Selective Reminding Test, the Modified Mini-Mental State Examination, Trails B, and category fluency. Depressed mood was assessed with the Beck Depression Inventory (BDI). A fasting blood sample was obtained for thyroid stimulating hormone (TSH) measurement. RESULTS: Mean age was 73.6 +/- 10.0 in men and 74.3 +/- 10.4 in women. Mean TSH was 1.9 mu IU/ml in both sexes; 9.0% of men and 24% of women reported thyroid medication use. Mean BDI scores were 4.6 +/- 4.1 in men and 5.2 +/- 4.3 in women; 9% of men and 11% of women used antidepressants. Before and after adjustment for covariates or exclusion of participants taking thyroid hormones, no associations were observed between TSH and cognitive function (ps > 0.10). TSH was inversely associated with BDI (p=0.03) in men, but not women. CONCLUSIONS: Thyroid stimulating hormone level was unrelated to cognitive function in men and women, and was inversely associated with depressed mood in men only, possibly reflecting the greater use of both thyroid medications and antidepressants by women.

Handedness and cognitive function in older men and women: a comparison of methods.

OBJECTIVE: Previous studies of handedness and cognitive function rely on self-classification and yield inconsistent results. This study examines the associations of self-reported versus grip-strength-based handedness with cognitive function in healthy older men and women. DESIGN: Cross-sectional study. SETTING: 1988-91 follow-up clinic visit and 1991 mailed survey. PARTICIPANTS: 684 men and 985 women aged 55-95 who were community dwelling. MEASUREMENTS: Cognitive function was assessed with 12 tests and grip strength was measured by hand-held dynamometer. Self-reported handedness was obtained with a mailed survey. RESULTS: By self-report, 92.1% of men and women were right-handed; 2.0% were left handed. By grip strength, in men, 64.3% were right-handed, 22.5% left-handed, and 13.2% ambidextrous. In women, 61.3% were right-handed, 17.3% left-handed, and 21.4% ambidextrous. No cognitive function differences were found by self-reported handedness in either sex (p's>0.10). However, based on grip strength, left-handed women scored poorer than right-handed or ambidextrous women in immediate and delayed memory, attention, and verbal fluency (p's<0.05). Using categorical definitions, left-handed or ambidextrous individuals based on grip strength were more likely to show poor cognitive function on 4 of 5 tests. CONCLUSION: Grip strength is a useful alternative to self-reports for classifying handedness. Left-handedness by grip-strength, may be related to poorer cognitive function; this association may vary by gender.

Plasma trace elements and cognitive function in older men and women: the Rancho Bernardo study.

OBJECTIVE: This study examines the sex-specific associations of plasma concentrations of iron, copper, and zinc with cognitive function in older community-dwelling adults. DESIGN: Cross-sectional study. SETTING: 1988-92 follow-up clinic visit. PARTICIPANTS: 602 men and 849 women (average age=75 +/- 8 years) who were community-dwelling and not clinically demented. MEASUREMENTS: Blood samples were assayed for trace elements and 12 cognitive function tests were administered. Sex-specific analyses were adjusted for age, education, alcohol consumption, smoking, exercise, and estrogen use in women. RESULTS: Men and women differed significantly in education and alcohol intake (p's < 0.001), concentrations of plasma iron, copper and zinc (p's < 0.001) and scores on 11 of 12 cognitive function tests (p=0.04 to < 0.001). Regression analyses showed significant inverted U-shaped associations in men; both low and high iron levels were associated with poor performance on total and long-term recall and Serial 7's (p's=0.018, 0.042 and 0.004, respectively) compared to intermediate concentrations. In women, iron and copper concentrations had inverse linear associations with Buschke total, long and short-term recall and Blessed scores (p's < 0.05). Zinc was positively associated with performance on Blessed Items (p=0.008). Analyses comparing cognitive function using categorically defined mineral concentrations yielded similar sex specific results. CONCLUSION: Optimal trace element concentrations may exist for optimal cognitive function in older adults, and these levels may differ by sex and cognitive function domain.

Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial.

UNLABELLED: We present results of a randomized, placebo-controlled trial to examine the effect of 50 mg daily oral DHEA supplementation for one year on bone mineral density (BMD), bone metabolism and body composition in 225 healthy adults aged 55 to 85 years. INTRODUCTION: Dehydroepiandrosterone (DHEA) levels decline dramatically with age, concurrent with the onset of osteoporosis, suggesting a role for DHEA supplementation in preventing age-related bone loss. METHODS: We conducted a randomized, placebo-controlled trial to examine the effect of 50 mg daily oral DHEA supplementation for one year on bone mineral density (BMD), bone metabolism and body composition in 225 healthy adults aged 55 to 85 years. RESULTS: DHEA treatment increased serum DHEA and DHEA sulfate levels to concentrations seen in young adults. Testosterone, estradiol and insulin-like growth factor (IGF-1) levels increased in women (all p < 0.001), but not men, receiving DHEA. Serum C-terminal telopeptide of type-1 collagen levels decreased in women (p = 0.03), but not men, whereas bone-specific alkaline phosphatase levels were not significantly altered in either sex. After 12 months, there was a positive effect of DHEA on lumbar spine BMD in women (p = 0.03), but no effect was observed for hip, femoral neck or total body BMD, and no significant changes were observed at any site among men. Body composition was not affected by DHEA treatment in either sex. CONCLUSION: Among older healthy adults, daily administration of 50 mg of DHEA has a modest and selective beneficial effect on BMD and bone resorption in women, but provides no bone benefit for men.

Breast cancer and bone mass in older women: is bone density prescreening for mammography useful?

INTRODUCTION: The utility of screening mammography for older women with low bone mineral density (BMD) is controversial. This case-control study compares BMD at multiple sites in women with and without breast cancer to determine if BMD prescreening is useful in selecting women for continued screening mammograms. METHODS: Women diagnosed with breast cancer in the preceding 4 months and age-matched controls (+/-2 years) with a normal mammogram, all aged 65 years and older, were recruited on a 1:2 basis; 237 women participated: 79 women (cases) with breast cancer and 158 controls. BMD at the lumbar spine, hip, radius, and whole body was measured with dual x-ray absorptiometry (DXA). RESULTS: Among women with breast cancer, 17.1% had stage 0, 41.5% stage I, 40.0% stage II, and 1.4% stage III. Women with breast cancer had larger waist circumferences (p=0.002) and waist-hip ratios (p=0.01), and they exercised less (p=0.002) than women of the control group. However, there were no differences between the cases and controls for age, obesity, and reproductive and menopausal history variables, or other covariates (p>0.10). There were no differences in lumbar spine, total hip, femoral neck, midshaft radius, or total body BMD (p>0.10), although the cases had higher BMD at the ultradistal radius than the controls (means: 0.527 vs. 0.516, respectively; p=0.014). There were no differences in breast cancer risk by tertile of BMD or osteoporosis status at the hip or spine. CONCLUSION: There is little difference in BMD between women with and without breast cancer. BMD is not useful as a prescreening predicator of mammography in older women and using it as such would result in cases of breast cancer being missed.

Expression of the rat renal PiT-2 phosphate transporter.

BACKGROUND: NaPi-2a is the main sodium-dependent Pi (Na+-Pi) transporter in the apical membrane of the renal proximal tubule. Another group of Pi transporters, Glvr-1 (PiT-1) and Ram-1 (PiT-2), was identified. The PiT-2 cRNA induces Na+-dependent Pi uptake into Xenopus laevis oocytes. Prior studies have revealed the presence of the Pit-2 transporter in the kidney. OBJECTIVES: Further characterization of the PiT-2 transporter in the kidney and assessment of its developmental regulation. METHODS: Using primers specific for the PiT-2 mRNA and an antibody specific for the PiT-2 protein, we assessed the expression and developmental regulation of the renal PiT-2 mRNA and protein. RESULTS: RT-PCR analysis revealed that a 182 bp product was evident in the total kidney (TK), cortex (C), and medulla (M). Northern blots demonstrated a PiT-2 mRNA of approximately 4 kb (expected size) in the TK, C, and M. PiT-2 mRNA expression was similar in all kidney regions. RT-PCR and Northern blot analysis revealed that the PiT-2 cDNA was highly abundant in OK and MDCK culture cells. RT-PCR and Northern blot analysis revealed expected products at all ages studied. Densitometry demonstrated similar levels of expression of PiT-2 mRNA in the kidneys of older versus younger animals, and persistent expression in elderly rats. The PiT-2 protein was present in the TK, C, and M, and in OK and MDCK cells. PiT-2 protein abundance was similar at all ages studied. CONCLUSIONS: These studies further characterize the renal PiT-2 transporter and show that its expression is stable throughout development and ageing.

Age at menarche, abnormal glucose tolerance and type 2 diabetes mellitus: The Rancho Bernardo Study.

OBJECTIVE: We examined the association of age at menarche with risk of abnormal glucose tolerance (AGT) and type 2 diabetes in postmenopausal women. METHODS: Participants were 997 women aged 50-92 years who had a clinic visit in 1984-87, when reproductive and diabetes history were recorded, and an oral glucose tolerance test administered. Information on age at menarche was collected in 1989. Diabetes status was based on WHO 1999 criteria, and AGT on having impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). RESULTS: The average age was 69.5 years; 12.5% had diabetes and 29.8% had AGT. Menarche was < 12 years in 14.5%, 12-15 years in 78.9% and > or = 16 years in 6.6%. Age and body mass index (BMI) predicted AGT (p < 0.001, p = 0.003, respectively), while age, BMI and family history of diabetes predicted type 2 diabetes (p < 0.001, p < 0.001, p = 0.02, respectively). Polynomial logistic regression showed no association of menarche with AGT or type 2 diabetes risk. In linear regressions, however, older age at menarche was associated with lower fasting (p = 0.01) and post-challenge plasma glucose (p = 0.03). Covariates, especially BMI, weakened these associations, although women with menarche > or = 16 years still had lower post-challenge (0.86 mmol/l, p = 0.05) and fasting glucose (0.26 mmol/l, p = 0.11) than those with menarche < 12 years. CONCLUSIONS: Age at menarche was not associated with AGT or type 2 diabetes risk. Late age at menarche was inversely associated with fasting and post-challenge glycemia. Obesity may mediate the observed associations.

Cumulative duration of breast-feeding influences cortisol levels in postmenopausal women.

Cortisol levels dramatically increase during pregnancy, peak at birth, and subsequently decline. However, all previous studies examined women during pregnancy and early postpartum. None examined the long-term association of parity and lactation with cortisol levels. We examined the relation of reproductive history to cortisol levels in postmenopausal women. Subjects were 749 women, aged 50-89, who were not using estrogen in 1984-1987 when morning cortisol was measured. Parity was not significantly associated with cortisol. However, women who breast-fed for >12 months had significantly higher cortisol levels than women who breast-fed for shorter durations or not at all (p = 0.003). This association was stronger among women with three or more births. Duration of breast-feeding is a determinant of cortisol levels in postmenopausal women. Because both increased cortisol and increased duration of breast-feeding may play protective roles in certain autoimmune diseases, such as rheumatoid arthritis, we suggest that the beneficial effect of lactation on the course of these diseases may be mediated by cortisol.

Are physicians aware of the risks of alternative medicine?

Evidence supports the fact that alternative medical therapies play an increasingly prominent role in healthcare. Relevantly, this study posed three questions: (1) Do physicians ask their patients about their use of herbs/dietary supplements? (2) Do physicians use the available resources to evaluate the possible drug interactions and/or side effects of the dietary supplements? and (3) Are physicians aware of the side effects, drug interactions and contraindications of ten commonly used herbs? A questionnaire was randomly distributed to medical students and faculty of the State University of New York, Health Science Center at Brooklyn. One hundred sixty five surveys were returned out of 193 handed out (85%). Analysis revealed that although many physicians asked their patients about their use of alternative remedies, most do not check the remedies in a reference text. Age and training were negatively correlated in a statistically significant manner with (1) the likelihood of a physician prescribing alternative medicines; (2) checking the side effects and drug interactions of over the counter and prescription medications in a reference text; (3) asking patients specifically about alternative medicines; and (4) checking the side effects and drug interactions of alternative remedies in a reference text. In a question matching ten herbs and side-effects, the highest score was six out of ten correct and the average number correct was 1.32 with a standard deviation of 1.39. Clearly, physicians may be aware of different forms of alternative medicines. However, physicians are still not treating herbs in the same manner as other types of medications. There is no doubt that patient care would be greatly enhanced if physicians educated themselves and stayed in touch with their patients' beliefs and health care behavior.

Renal morphology in connexin43 knockout mice.

Connexins (Cx) are a family of proteins that constitute the intercellular membrane channels of gap junctions. These junctions permit intercellular movement of ions and other molecules between cells, a property vital to organogenesis. Cx43 is a member of the family of channel-forming proteins that are essential for cell-cell communication of developmental signals. Studies demonstrate that Cx43 is observed in mesenchymal cells of 12-day gestation mouse kidney, a crucial period of renal development. In order to study the significance of Cx43 on renal developmental morphology, we evaluated the kidneys of embryos lacking the gene encoding for Cx43. Polymerase chain reaction (PCR) from tail specimens identified wild-type (WT), heterozygote (HT) and knockout (KO) progeny. In situ RT-PCR displayed abundant Cx43 staining in glomeruli, vasculature, and tubules in kidneys obtained from WT progeny. In contrast, Cx43 expression was completely absent in kidneys isolated from the KO. Renal histology in all three groups displayed no significant differences. Renal size was similar and there was no evidence of dysplasia or cyst formation in the KO. Our results indicate that absence of Cx43, heretofore considered essential for renal development, does not affect early renal morphological development.

Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women.

Intervention data suggest a cardioprotective role for supplemental isoflavones; however, few studies have examined the cardiovascular disease (CVD) benefit of usual dietary isoflavone intake. This cross-sectional study examined the association between usual dietary isoflavone intake and CVD risk factors, including lipids and lipoproteins, body mass index (BMI) and fat distribution, blood pressure, glucose and insulin. Subjects were postmenopausal women (n = 208) aged 45-74 y, who attended screening and baseline visits for a randomized, double-blind, placebo-controlled trial examining the effects of isoflavone use. At screening, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol were measured, and demographic, behavioral and menopausal characteristics were assessed. One month later, dietary intake over the past year was assessed with a standardized questionnaire. Anthropometric measurements and blood pressure were obtained, and a 75-g oral glucose tolerance test was administered. Isoflavone consumption did not vary by age, exercise, smoking, education or years postmenopausal. Women with high genistein intake had a significantly lower BMI (P-trend = 0.05), waist circumference (P-trend = 0.05) and fasting insulin (P-trend = 0.07) than those with no daily genistein consumption. In adjusted analyses, genistein, daidzein and total isoflavone intake were each positively associated with HDL cholesterol (P = 0.05) and inversely associated with postchallenge insulin (P = 0.05). These data suggest a protective role for dietary soy intake against CVD in postmenopausal women.

Cross-sectional and prospective study of exercise and depressed mood in the elderly : the Rancho Bernardo study.

This study examined cross-sectional and prospective associations of exercise with depressed mood in a community-based sample of older men and women (aged 50--89 years in 1984--1987) in southern California. Regular strenuous exercise and exercise > or =3 times per week were reported; depressed mood was assessed by using the Beck Depression Inventory (BDI). After exclusion of persons with categorical depression and those rating themselves largely or extremely physically limited during the previous month, data on 932 men and 1,097 women were available for cross-sectional analysis. Exercise and depressed mood were reassessed for 404 men and 540 women in 1992--1995; these data were the focus of prospective analyses. In 1984--1987, exercise rates were high (>80%), and average BDI scores were low. Cross-sectional analyses indicated that before and after adjustment for covariates, exercise was significantly associated with less depressed mood. However, prospective analyses of the 944 persons who attended both clinic visits indicated no association between baseline exercise and either follow-up BDI score (p > 0.10) or change in BDI score between baseline and follow-up (p > 0.10). Results confirm that exercisers have less depressed mood. However, exercise does not protect against future depressed mood for those not clinically depressed at baseline.

Higher basal cortisol predicts verbal memory loss in postmenopausal women: Rancho Bernardo Study.

BACKGROUND: In animals, higher endogenous or exogenous corticosteroids cause neuronal dysfunction, damage, and loss, especially in the hippocampus. In humans, high cortisol levels have been linked to memory impairment. OBJECTIVE: To prospectively examine the relation between morning basal cortisol level and change in cognitive performance during an average follow-up of 2 years. DESIGN: Longitudinal cohort. SETTING: Geographic community in southern California. MEASUREMENTS: Between 1984 and 1987, blood for basal morning cortisol was obtained along with pertinent medical, behavioral, and physical covariates from 749 post-menopausal women, mean age 72 years, who were not taking corticosteroids or postmenopausal hormones. Cognitive function was assessed in 502 women in the period from 1988 to 1991 and repeated in 136 women in the period from 1991 to 1993. RESULTS: In both age- and multiply adjusted linear regression models, higher baseline cortisol was a significant predictor of worsened category fluency. No other cognitive domain tested was related to cortisol. CONCLUSIONS: These results support the hypothesis that subtle dysregulation of cortisol axis is related to memory loss. Interventions that block this pathway may provide new therapeutic options to prevent cognitive decline.