[Exploring a definition of healthy longevity in Chinese population based on Delphi method].

Objective: To explore a definition of healthy longevity in the Chinese population based on the Delphi method. Methods: Through a comprehensive literature review and expert consultation, the dimensions in the definition of healthy longevity were identified, and a preliminary list of questions was created. Experts in clinical medicine, public health, basic research, and the elderly care service industry, who had been working in the field of geriatric health for at least 5 years, were invited to participate in the Delphi survey from August to December 2022. The survey questionnaires were administered via email in two rounds, and experts were asked to select the optimal options from the provided questions. The active coefficients were expressed by the response rate, and a consensus was reached when the largest number of experts agreed for single-choice questions and more than 70% agreed for multiple-choice questions. Results: In the two rounds, the active coefficients were 96.00% (24/25) and 79.17% (19/24), respectively, and a consensus was finally reached on nine items, including age, physical health, common metabolic indicators, mental health, cognitive function, functional ability, social activity, self-rated health, and subjective well-being. Following discussions among the research team and experts, a final definition of healthy longevity was determined. Healthy longevity could refer to a state of good physical, psychological, cognitive function and social adaptation, as well as subjective well-being, in individuals aged 90 and above. Specifically, individuals with healthy longevity should be free from diseases associated with high disability rates and mortality, such as stroke, cancer, and Parkinson's disease. They should also maintain reasonable levels of common non-communicable disease indicators, such as blood pressure and blood glucose, and exhibit favorable mental health and cognitive function using validated measurement tools. In addition, individuals with healthy longevity should engage in social interactions with friends and relatives, care for family members, and go out to do things. Meanwhile, with the ability to complete the visual and hearing functions of daily life and communication, and the ability to complete basic activities such as walking, eating, bathing, toileting, dressing, continence of urination, and bowel movement independently, they could rate themselves to be in good health and experience a relatively high level of life satisfaction. Conclusion: A definition of healthy longevity in the Chinese population is established through the two-round Delphi consultation.

[Association between cognitive impairment and main metals among oldest old aged 80 years and over in China].

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 µg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q1) of blood selenium, the ORs (95%CI) of Q3 and Q4 blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (Pnonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.

[Distribution characteristics of body mass index among Chinese oldest-old aged 80 years and above].

Objective: To investigate body mass index (BMI) level, identify the main type of nutritional problem, and describe the population distribution characteristics of BMI among Chinese people aged 80 years or above. Methods: The data of 9 481 oldest-old individuals were obtained from the 2017-2018 Chinese Longitudinal Healthy Longevity Survey. The Lambda-Mu-Sigma method, weighted estimates of BMI, and comparisons by BMI quintiles were used to describe the BMI level and distribution characteristics among the oldest-old. Results: The average age of the participants was (91.9±7.7) years, with P50 of the weighted BMI at 21.9 (95%CI: 21.8-22.0) kg/m2. The result of BMI level showed a decreasing trend with age, with a rapid decline before age 100, and then the trend became slower. There are about 30% of the oldest-old classified as undernutrition, but the prevalence of overnutrition is only about 10%. The population distribution characteristics by BMI quintiles showed the oldest-old with lower BMI levels were likely to have the following characteristics: sociodemographically, to be older, female, ethnic minority, unmarried/divorced/widowed, rural residents, illiterate, with inadequate living expenses, located in Central, South, or Southwest China; regarding lifestyles, lower BMI levels were observed for participants who were smoking, not exercising, lack of leisure activities, or with poor dietary diversity; considering functional status, participants with lower BMI levels were those who have poor chewing ability, disability in activities of daily living, cognitive impairment, hearing loss, visual impairment, or poor self-rated health status. The oldest-old with higher BMI levels were likely to have heart disease, hypertension, cerebrovascular disease, and diabetes. Conclusions: The overall BMI level was low among the Chinese oldest-old and it showed a downward trend with age. Currently, the main nutritional problem among the Chinese oldest-old was undernutrition rather than overweight or obesity. Management of healthy lifestyles, functional status, and diseases would be helpful to reduce the risk of undernutrition among the oldest-old.

[Association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China].

Objective: To investigate the association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 in 9 longevity areas of China. Methods: The elderly over 65 years old with complete information on plasma vitamin B12 and plasma uric acid from Healthy Aging and Biomarkers Cohort Study (2017 to 2018) were recruited in this study. Information on socio-demographic characteristics, life styles, diet intake, and health status were collected by questionnaire and physical examination; and fasting venous blood was collected to detect the levels of plasma vitamin B12, uric acid and other indicators. Multiple linear regression models were used to analyze the association of plasma vitamin B12 level per interquartile range increase with plasma uric acid level. The association trend of plasma vitamin B12 level with plasma uric acid level was described by restrictive cubic splines fitting multiple linear regression model. Multiple logistic regression models were used to analyze the association of plasma vitamin B12 level stratified by quartiles with hyperuricemia. Results: A total of 2 471 participants were finally included in the study, the age was (84.88±19.76) years old, of which 1 291 (52.25%) were female. The M (Q1, Q3) level of plasma vitamin B12 was 294 (203, 440) pg/ml and the plasma uric acid level was (341.01±90.46) µmol/L. A total of 422 participants (17.08%) were defined with hyperuricemia. The results of multiple linear regression model showed that there was a positive association of plasma vitamin B12 level with plasma uric acid level after adjustment for covariates (P<0.05). An IQR increase in plasma vitamin B12 (237 pg/ml) was associated with a 6.36 (95%CI: 2.00-10.72) µmol/L increase in the plasma uric acid level. The restrictive cubic splines curve showed a positive linear association of log-transformed plasma vitamin B12 with uric acid level (P<0.001). Conclusion: There is a positive association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China.

[Association of greenness, nitrogen dioxide with the prevalence of hypertension among the elderly over 65 years old in China].

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO2) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO2 was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO2 for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO2 as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO2 and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO2 concentration was (32.18±10.36) µg/cm3. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T1 group of NDVI, the risk of hypertension was lower in the T3 group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T1 group of NO2, the risk of hypertension was higher in the T2 and T3 groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO2 was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO2 had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO2 are associated with hypertension in older adults.

[Association of greenness exposure with waist circumference and central obesity in Chinese adults aged 65 years and over].

Objective: To examine the association of greenness exposure with waist circumference (WC) and central obesity in older adults in China. Methods: Based on the cross-sectional data from the Chinese Longitudinal Healthy Longevity Survey in 2017-2018, 14 056 participants aged 65 years and over were included. Demographic characteristics, lifestyle, WC, and other information were collected through a questionnaire and physical examination. Based on the satellite monitoring data of moderate-resolution imaging spectroradiometer (MODIS) provided by NASA, the annual mean of normalized difference vegetation index (NDVI) within a radius of 1 000 meters was obtained as the measurement value of greenness exposure. Multivariate linear regression model, multivariate logistic regression model, and restricted cubic splines (RCS) model were used to analyze the association and dose-response relationship between greenness exposure and WC and central obesity in older adults in China. Results: A total of 14 056 participants were enrolled with a median age of 84.0 years [IQR: 75.0-94.0 years]. About 45.0% (6 330) of them were male and 48.6% (5 853) were illiterate. There were 10 964 (78.0%) participants from rural. The mean of WC was (84.4±10.8) cm. Central obesity accounted for 60.2% (8 465), and the NDVI range was (-0.06, 0.78). After adjusting for confounding factors, the multivariate linear regression model showed that the change value of WC in the urban group [ß (95%CI):-0.49 (-0.93, -0.06)] was smaller than that in the rural [-0.78 (-0.98, -0.58)] for every 0.1 unit increase in NDVI (Pinteraction=0.022). Compared with the Q1 group in NDVI, WC of Q2 and Q3 groups in rural decreased, and the ß (95%CI) values were-1.74 (-2.5, -0.98) and-2.78 (-3.55, -2.00), respectively. The multivariate logistic regression model showed that after adjusting for confounding factors, the risk of central obesity decreased for urban and rural older adults with an increase of 0.1 unit in NDVI, and the OR (95%CI) values were 0.87 (0.80, 0.95) and 0.86 (0.82, 0.89), respectively (Pinteraction=0.284). Compared with the Q1 group in NDVI, the risk of central obesity in the Q2 and Q3 groups in rural was lower, and the OR (95%CI) values were 0.68 (0.58, 0.80) and 0.57 (0.49, 0.68), respectively. The results of the multivariate regression model with RCS showed that there was a non-linear association of NDVI with WC (Pnonlinear=0.006) and central obesity (Pnonlinear=0.025). Conclusion: Greenness exposure is negatively associated with WC and central obesity in older adults in China.

[Association of body mass index and waist circumference with frailty among people aged 80 years and older in Chinese].

Objective: To examine the association of body mass index (BMI) and waist circumference (WC) with frailty among oldest-old adults in China. Methods: A total of 7 987 people aged 80 years and older (oldest-old) who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2017-2018 were included. Information on demographic characteristics, behavior pattern, diet, activities of daily living, cognitive function, health status, disease condition were collected by questionnaire and physical examination. Generalized linear mixed model and restricted cubic splines (RCS) were used to analyze the association of BMI and WC with frailty. Results: The mean age of all participants was 91.7 years, and their mean BMI and WC were (21.3±3.5) kg/m2 and (82.9±10.5) cm, respectively. The proportion of male was 42.3% (3 377/7 987), and the proportion of people with frailty was 33.7% (2 664/7 987). After controlling confounding factors, compared with T2 (19.1-22.1 kg/m2) of BMI, the OR (95%CI) of the female T1 (<19.1 kg/m2) and T3 (≥22.2 kg/m2) group was 1.39 (1.17-1.65) and 1.27 (1.07-1.52), respectively. Compared with T2 (77-85 cm) of WC, the OR (95%CI) of female T1 (<77 cm) and T3 (≥86 cm) group was 1.20 (1.01-1.42) and 1.10 (0.93-1.31), respectively. The results of multiple linear regression model with restrictive cubic spline showed that there was a non-linear association of BMI and WC with frailty in female. Conclusion: There is a U-shaped association of BMI and WC with frailty in female participants.

[The purchase behavior of prepackaged food and its determinants among primary and middle school students in 6 provinces of China].

Objective: To examine the purchase behaviors of prepackaged food and its determinants among primary and middle school students in 6 provinces of China. Methods: A multi-stage sampling strategy was adopted to select 2 499 primary and middle school students and their parents from the eastern region of China(Beijing, Jiangsu Province, Guangdong Province), the northeast region(Heilongjiang Province), the central region(Henan Province) and the western region(Sichuan Province) from July 2020 to March 2021. Socio-demographic characteristics of students and their parents, eating-related behaviors and the purchase behaviors of prepackaged food of students, and parents' attitudes towards students' eating behavior were collected through questionnaire towards students and their parents. The χ² test was conducted to compare the purchase behaviors in different groups of students, and multivariate logistic stepwise regression analysis was used to analyze the determinants among primary and middle school students. Results: The age of 2 499 participants was(12.7±2.5) years. There were 1 272(50.9%) females and 1 279(51.2%) middle school students. About 1 404(56.2%) students bought prepackaged food. The top 6 prepackaged foods bought at least once a week were milk and dairy products(74.6%), baked food(58.7%), beverages(42.8%), puffed food(40.8%), chocolate and candy(39.8%), and nuts and dried fruits(37.5%). The multivariate logistic regression model analysis results showed that compared with primary school students, rural students, non-boarding students, students who did not like snacks and students whose parents paid attention to their children eating snacks, middle school students(OR=3.36, 95%CI:2.73-4.12), urban students(OR=1.33, 95%CI:1.11-1.61), boarding students(OR=2.15, 95%CI:1.66-2.79), students who liked snacks(OR=2.01, 95%CI:1.66-2.43), students whose parents did not pay attention to their children eating snacks(OR=1.27, 95%CI:1.05-1.54) were more likely to buy prepackaged food by themselves. Compared with students whose parents had education level of junior high school and below, students whose parents had education level of undergraduate and above(OR=0.70, 95%CI:0.53-0.92) were less likely to buy prepackaged food by themselves. Compared with students whose family monthly income was less than 5 000 yuan, students whose family monthly income was over 10 000 yuan(OR=0.67, 95%CI:0.52-0.87) were less likely to buy prepackaged food by themselves. Conclusion: Many primary and middle school students buy prepackaged food by themselves in 6 provinces of China. Individual characteristics such as grade, place of residence, boarding status, as well as family environment such as parents' education level, monthly income and concern about children eating snacks are the influencing factors of purchasing prepackaged food.

[Association between the awareness of Nutrition Facts Panel and prepackaged food purchase behavior among residents].

Objective: To explore the association between the cognition of Nutrition Facts Panel and prepackaged food purchase behavior among residents in six provinces in China. Methods: Using a multi-stage sampling method, 3 002 adults aged 18-70 were selected from the western region (Sichuan), eastern region (Guangdong, Jiangsu, Beijing), central region (Henan), and northeastern region (Heilongjiang) of China from July 2020 to March 2021. Socio-demographic characteristics of participants and their cognition of Nutrition Facts Panel and prepackaged food purchase behavior were collected through questionnaire. A multivariate binary logistic regression model was used to analyze the association between cognition of Nutrition Facts Panel and prepackaged food purchase behavior. Results: The age of 3 002 subjects was (42.3±13.4) years, among which 63.8% (1 914) were female, 66.7% knew the Nutrition Facts Panel, 49.8% would read it when purchasing, 30.7% could understand it, and 56.6% (1 699) bought prepackaged food more than once a week. The results of multivariate analysis showed that after adjusting for relevant confounding factors, compared with the participants knowing but not reading the Nutrition Facts Panel, the group knowing and reading was more likely to buy 11 types of prepackaged food at least once a week (all P<0.05). Compared with the participants reading but not understanding the Nutrition Facts Panel, the group reading and understanding was less likely to buy 11 types of prepackaged food at least once a week (all P<0.05). Conclusion: There was a correlation between cognition of Nutrition Facts Panel and prepackaged food purchase behavior among residents.

[The preference for Front-of-Pack Labeling and its association with the understanding of Nutrition Facts Panel among residents aged 18 to 70: results of a survey in 6 provinces of China].

Objective: To investigate the preference for Front-of-Pack Labeling (FOP) and its association with the understanding of the Nutrition Facts Panel among Chinese residents. Methods: A multi-stage sampling strategy was adopted to select 3 002 people aged between 18 and 70 years old from the eastern region of China (Beijing, Jiangsu Province, Guangdong Province), the northeast region (Heilongjiang Province), the central region (Henan Province) and the western region (Sichuan Province) from July 2020 to March 2021. Socio-demographic characteristics of participants and their understanding of the Nutrition Facts Panel and preference for FOP were collected. The χ² test was conducted to compare the preference for FOP in different groups of population, and multivariate logistic regression was used to analyze the association between the preference for FOP and the understanding of the Nutrition Facts Panel. Results: The mean age of 3 002 participants was (42.3±13.4) years, of which 1 914 (63.8%) were females and 69.3% could not understand the Nutrition Facts Panel. About 2 458 respondents (81.9%) suggested that FOP could be promoted. The top three nutrients that should be labeled were sugar (68.4%), salt (68.2%) and total fat (62.4%). The number of participants who believed that the Multiple Traffic Lights (MTL) could be easier to help consumers to quickly choose healthy food, attract attention and provide the most needed information was 1 064 (35.4%), 1 026 (34.2%) and 1 140 (38.0%), respectively. The multivariate logistic regression analysis showed that, compared with the Guideline Daily Amount (GDA) system, participants who could not understand the Nutrition Facts Panel preferred (1) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could quickly help you choose food more easily?"[OR (95%CI): 2.21 (1.62-3.02), 1.64 (1.22-2.22), 1.79 (1.31-2.45), respectively]; (2) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could attract your attention the most?"[OR (95%CI): 2.62 (1.92-3.59), 1.96 (1.45-2.66), 2.25 (1.66-3.04), respectively]; and (3) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could provide you with the most needed information?"[OR (95%CI): 2.33 (1.70-3.21), 2.21 (1.66-2.95), 2.01 (1.50-2.71), respectively]. Conclusion: The residents from six provinces in China have a supportive attitude towards FOP. The interpretive FOP with color information, specific nutrient information and summary indicator can be launched. The nutrition information of sugar, salt and total fat could be prioritized to be labeled on the FOP.

[Prediction of 6-year risk of activities of daily living disability in elderly aged 65 years and older in China].

Objective: To construct an easy-to-use risk prediction tool for 6-year risk of activities of daily living(ADL) disability among Chinese elderly aged 65 and above. Methods: A total of 34 349 elderly aged 65 and above were recruited from the Chinese Longitudinal Healthy Longevity Survey. Demographic characteristics, lifestyle and chronic diseases of the elderly were collected through face-to-face interviews. The functional status of the elderly was evaluated by the instrumental activities of daily living(IADL) scale. The mental health status of the elderly was evaluated by the Mini-Mental State Examination. The height, weight, blood pressure and other information of the subjects were obtained through physical examination and body mass index(BMI) was calculated. The ADL status was evaluated by Katz Scale at baseline and follow-up surveys. Taking ADL status as the dependent variable and the key predictors were selected from Lasso regression as the independent variables, a Cox proportional risk regression model was constructed and visualized by the nomogram tool. Area under the receiver operating characteristic curve(AUC) and calibration curve were used to evaluate the discrimination and calibration of the model. A total of 200 bootstrap resamples were used for internal validation of the model. Sensitivity analysis was used to evaluate the robustness of the model. Results: The M(Q1, Q3) of subjects' age as 86(75, 94) years old, of which 9 774(46.0%) were males. A total of 112 606 person-years were followed up, 4 578 cases of ADL disability occurred and the incidence density was 40.7/1 000 person-years. Cox proportional risk regression model analysis showed that older age, higher BMI, female, hypertension and history of cerebrovascular disease were associated with higher risk of ADL disability [HR(95%CI) were 1.06(1.05-1.06), 1.05(1.04-1.06), 1.17(1.10-1.25),1.07(1.01-1.13) and 1.41(1.23-1.62), respectively.]; Ethnic minorities, walking 1 km continuously, taking public transportation alone and doing housework almost every day were associated with lower risk of ADL disability [HR(95%CI): 0.71(0.62-0.80), 0.72(0.65-0.80), 0.74(0.68-0.82) and 0.69(0.64-0.74), respectively]. The AUC value of the model was 0.853, and the calibration curve showed that the predicted probability was highly consistent with the observed probability. After excluding non-intervening factors(age, sex and ethnicity), the AUC value of the model for predicting the risk of ADL disability was 0.779. The AUC values of 65-74 years old and 75 years old and above were 0.634 and 0.765, respectively. The AUC values of the model based on walking 1 km continuous and taking public transport alone in IADL and the model based on comprehensive score of IADL were 0.853 and 0.851, respectively. Conclusion: The risk prediction model of ADL disability established in this study has good performance and robustness.

Suspended aggregates as an immobilization mode for high-density perfusion culture of HEK 293 cells in a stirred tank bioreactor.

Cells of the human embryonic kidney cell line (HEK 293) grown in repeated suspension and perfusion systems were characterized and described. Cell aggregates that formed immediately after the HEK 293 cells were inoculated in stirred vessels in serum-containing Dulbecco's modified Eagle's medium (D-MEM)/F-12 medium. The mean diameter of the cell aggregates reflecting the aggregate size increased with culture time, shifting from 63 to 239 mum after 1 and 8 days of culture in spinner flasks, respectively. No significant differences in cell performance were observed between HEK 293 cell populations grown as suspended aggregates and those grown as anchored monolayers. Replacing the D-MEM/F-12 with CD 293 medium caused the compact spherical cell aggregates to dissociate into single cells and small irregular aggregates without any apparent effect on cell performance. Moreover, the spherical cell aggregates could reform from individual cells and small aggregates when exposed to the serum-containing D-MEM/F-12 dominant medium. Perfusion culture of HEK 293 cells grown as suspended aggregates in a 7.5-l stirred tank bioreactor for 17 days resulted in a maximum viable cell density of 1.2 x 10(7) cells ml(-1). These results demonstrate the feasibility and proof-of-concept for using aggregates as an immobilization system in large-scale stirred bioreactors because a small-scale culture can be used as easily as the inoculum for larger bioreactors.

Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome.

During a study of the familial aggregation of Down syndrome (DS) and Alzheimer disease (AD), we observed an increase in mosaicism for disomy 21 in older individuals with DS. In a total of 213 DS subjects who were studied cytogenetically, only 1 of 121 (0.8%) under age 45 exhibited mosaicism, while 14 of 92 (15.2%) who were age 45 or older had mosaicism. Mosaicism in this report connotes "low-level" mosaicism, where all 15 individuals exhibited a modal chromosome number of 47 (i.e., trisomy 21), and at least two cells lacked one of the three chromosomes 21. The occurrence of aneuploidy for chromosomes 15, 17, and X increased with age, and an inverse correlation between chromosome loss and size was also observed. Because older individuals had not been karyotyped at birth, it was not possible to determine whether our observations were due to either increased survival of mosaic individuals or accumulation of disomy 21 cells via increased chromosome loss with aging of the trisomy 21 individual. Using a modeling approach involving life table methods, we obtained results that suggested acquired mosaicism as the predominant mechanism to explain our findings. These results support the hypothesis that as individuals with DS age, there is an increased loss of chromosome 21.

Familial transmission of the FMR1 CGG repeat.

To better define the nature of FMR1 CGG-repeat expansions, changes in allele sizes for 191 families with fragile X and for 33 families with gray-zone repeats (40-60) were analyzed. Expansion of the fragile X chromosome to the full mutation was seen in 13.4% of offspring from premutation mothers with 56-59 repeats, 20.6% of those with 60-69 repeats, 57.8% of those with 70-79 repeats, 72.9% of those with 80-89 repeats, and 97.3% of those with 90-199 repeats. For premutation fathers, the majority (62%) of their daughters had a larger repeat number, while a few had either a smaller (22%) or the same (16%) repeat number, compared with their fathers' sizes. However, daughters with a smaller repeat number were observed only if their fathers had > or = 80 repeats. Fifteen (39.5%) of 38 such daughters carried a smaller repeat than did their fathers. We observed that a similar repeat number was inherited more often than expected by chance, among the members of a sibship segregating fragile X. This familial clustering, observed in the offspring of both males and females with a premutation, implies there may be an additional factor, independent of parental repeat size, that influences CGG-repeat instability. Instability in gray-zone allele transmissions was observed in 25% of alleles with 50-60 CGGs but in <8% of those with 40-49 CGGs. Examination of gray-zone allele organization revealed that long tracts of pure CGGs (>34) are not always unstably transmitted. These results raise new questions regarding the familial factors that may determine transmission expansions.

[Alpha-receptor mediated effect of injection of norepinephrine into hippocampus on plasma cortisol level in cats].

In the present experiment, the effect of injection of NE into the different areas of hippocampus on the plasma cortisol level and the kind of NE receptor involved were studied in 83 cats anesthetized with Nembutal. The plasma cortisol level was increased following injection of NE into the ventral hippocampus (VHIP), however, there was no significant change when injection was made into dorsal hippocampus. The NE-VHIP effect can be blocked by injection of phentolamine, yohimbine or prazosin but not by propranolol. Thus, these results show that, in the regulation of the plasma cortisol level, the alpha-receptor system of VHIP is more specifically involved.

[A new therapy of hemophilia with ranitidine].

20 cases of hemophilia, including ten of hemophilia A , nine of hemophilia B and one of von Willebrand's disease (VWD), were treated with ranitidine. The results revealed that the levels of both factor VIII and IX were increased and the clinical symptoms of bleeding were ameliorated. The level of factor VIII in hemophilia A ranged from 5.27 +/- 3.94% before treatment and rose to 14.68 +/- 4.70% during the treatment period (P less than 0.001). The level of the factor IX in the patients with hemophilia B increased from 4.42 +/- 3.01% before treatment to 20.33 + 9.31% under treatment (P less than 0.001). Tn the patient with VWD the level of the factor VIII rose but the level of von Willebrand factor did not change. The drug has no side effect. The results of our study suggests that ranitidine therapy is effective and safe in hemophilia.