The efficacy and safety of venetoclax combined with demethylating agents in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. MATERIALS AND METHODS: A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety. RESULTS: 10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment. CONCLUSIONS: The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.

The efficacy and safety of triplet regimens based on pomalidomide and dexamethasone for treatment of relapsed/refractory multiple myeloma: a systematic review and meta-analysis.

OBJECTIVE: Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very clear. This meta-analysis aimed at comparing the safety and efficacy of different triplet therapies and analyzing the best therapy regimen. MATERIALS AND METHODS: A comprehensive literature search identified a total of 615 studies, and 22 studies assessing 1,889 subjects met the inclusion criteria of this meta: phase II/III trial, over 2 median lines of prior therapy, and detailed efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival (PFS). All statistical analyses were performed by Revman version 5.3, and the heterogeneity was tested by I2 (25% indicating low heterogeneity, 50% moderate, and 75% high). For those with less heterogeneity, fixed-effect model was used. With a significant high heterogeneity, a random-effect model was used. RESULTS: Pooled analysis showed ORR 66.2% across all triplet regimens based on pomalidomide and dexamethasone. Among all triplet regimens, therapy containing bortezomib showed the highest ORR (90.3%), and the one containing elotuzumab showed the lowest ORR (41.2%). The pooled ORRs for the remaining treatment regimens are as follows: cyclophosphamide (70.1%), isatuximab (66.3%), daratumumab (61.2%), clarithromycin (60.0%), pembrolizumab (47.3%). A total of 21 adverse events appeared in the included studies, with neutropenia being the highest incidence of hematologic adverse events (32.1%) and cough being the highest incidence of non-hematologic adverse events (43.3.%). CONCLUSIONS: Three-drug regimens based on pomalidomide and dexamethasone could yield excellent overall response rate to relapsed/refractory multiple myeloma, but there are still various adverse events; therefore, consequent studies should address these adverse events.

Dynamics of cytokines and lymphocyte subsets associated with the poor prognosis of severe COVID-19.

OBJECTIVE: We aimed to study the dynamics of cytokines and lymphocyte subsets and their correlation with the prognosis of patients with severe COVID-19. PATIENTS AND METHODS: The lymphocyte subsets and cytokines of 31 patients with severe COVID-19 (7 deaths and 24 survivals) were longitudinally analyzed. RESULTS: The mean age of enrolled patients was 64 years, 24 (77.4%) patients were men, and 23 (74.2%) patients had comorbidities. Compared with survival group, the death group showed significant and sustained increases in the levels of IL-6, IL-8, and IL-10 from baseline to 28 days after admission (all p<0.05). No significant differences were observed in the levels of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-12P70, IL-17, IFN-α, and IFN-γ between the death group and survival group during the follow-up (all p>0.05). The absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD45+ T cells were lower in both survival group and death group patients from hospital admission to 3 days after admission, and gradually recovered in 4 to 35 days in the survival group, but continually stayed at low levels in the death group during the follow-up. CONCLUSIONS: The kinetic changes of cytokines and lymphocyte subsets are related with the prognosis of patients with severe COVID-19.

MicroRNA-149 inhibits the progression of lung adenocarcinoma through targeting RAP1B and inactivating Wnt/ß-catenin pathway.

OBJECTIVE: MicroRNAs (miRNAs) are important regulators in the progression of lung adenocarcinoma (LAD). Moreover, microRNA-149 (miR-149) exhibits different roles in human cancers. Hence, this study mainly focused on the function of miR-149 in LAD. PATIENTS AND METHODS: Western blot analysis and Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) were used to quantify expression levels. The regulatory mechanism of miR-149/RAP1B was explored by methyl thiazolyl tetrazolium (MTT), transwell, and Dual-Luciferase reporter assays. RESULTS: Downregulation of miR-149 was detected in LAD and predicted worse prognosis in patients with LAD. Functionally, overexpression of miR-149 inhibited cell viability and metastasis in LAD. In addition, miR-149 directly targets RAP1B and restrained its expression in LAD. Furthermore, upregulation of RAP1B attenuated the inhibitory effect of miR-149 on LAD. Besides that, miR-149 blocked epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathway in LAD. CONCLUSIONS: MiR-149 inhibited the progression of LAD by restraining RAP1B/EMT and inactivating Wnt/ß-catenin pathway.

Survival after neoadjuvant chemoradiotherapy and oesophagectomy versus definitive chemoradiotherapy for patients with oesophageal squamous cell carcinoma.

BACKGROUND: Whether there is a difference in survival after neoadjuvant chemoradiotherapy plus surgery (CRT-S) compared with definitive chemoradiotherapy (dCRT) in patients with locally advanced oesophageal squamous cell carcinoma (SCC) remains controversial. METHODS: Patients with SCC who underwent curative treatment from 2008 to 2014 were identified from the Taiwan Cancer Registry. Propensity score matching was undertaken to balance pretreatment clinical variables. Overall survival was compared between patients undergoing CRT-S or dCRT. Univariable and multivariable analyses were performed to identify prognostic factors for overall survival. RESULTS: A total of 5832 patients with clinical stage II and III oesophageal SCC receiving CRT-S (1754) or dCRT (4078) were included. After propensity score matching, each group included 1661 patients. The 3-year overall survival rate for patients treated with CRT-S was 41·1 per cent compared with 17·9 per cent for those who had dCRT (P < 0·001). In multivariable analysis, treatment modality was an independent prognostic factor in the overall cohort before propensity score matching: hazard ratio 0·45 (95 per cent c.i. 0·40 to 0·51) for CRT-S versus dCRT (P < 0·001). In separate analyses of patients with clinical stage II and those with stage III disease, CRT-S was associated with significantly better overall survival than dCRT. CONCLUSION: Neoadjuvant chemoradiotherapy and oesophagectomy is associated with better overall survival than dCRT in patients with stage II and III oesophageal SCC.

[Fujian Tulou Family Cohort Study: study design and characteristics of participants and pedigrees in baseline investigation].

Objective: To describe the study design, the characteristics of participants as well as the pedigrees included in the baseline survey of Fujian Tulou Family Cohort Study. Methods: Fujian Tulou Family Cohort Study was a prospective open cohort study with a biological sample bank. A baseline survey was conducted in Tulou areas of Nanjing county in Fujian province from 2015 to 2018, including questionnaire survey, physical and biochemical indicators examinations, and blood sample collection in adults aged ≥18 years. In addition, family relationship of the participants was also recorded. The pedigree information of the juveniles under 18 years old were also collected. Results: The baseline survey included 2 727 individuals in two clans, of whom 2 373 (87.0%) were adults, and 2 126 participants completed questionnaires, physical examinations and biochemical tests. The average age of the 2 126 participants was (57.9±13.3) years, with 39.4% being males. The current smoking rates in male and female participants were 41.2% and 2.1%, respectively. The corresponding rates of current alcohol consumption were 19.0% and 2.6%. For common chronic diseases, the prevalence rates were 51.3% for hypertension, 9.7% for diabetes and 26.7% for hyperlipemia according to the self-reported disease diagnoses, health examination results and biochemical examination results in class Ⅱ or Ⅲ hospitals. Based on the family relationship information and genealogical data, 710 pedigrees were finally identified, consisting of 5 087 family members. The numbers of five, four, three, and two generations pedigrees were 3, 88, 238 and 381, respectively. The pairs of the first to the fifth degree relatives were 12 039, 2 662, 1 511, 202 and 31, respectively. Conclusion: The establishment of Fujian Tulou Family Cohort provides valuable resources for exploring the genetic risk factors, environmental risk factors and gene-environment interactions contributing to the risk of common chronic diseases.

What effect do substorms have on the content of the radiation belts?

Substorms are fundamental and dynamic processes in the magnetosphere, converting captured solar wind magnetic energy into plasma energy. These substorms have been suggested to be a key driver of energetic electron enhancements in the outer radiation belts. Substorms inject a keV "seed" population into the inner magnetosphere which is subsequently energized through wave-particle interactions up to relativistic energies; however, the extent to which substorms enhance the radiation belts, either directly or indirectly, has never before been quantified. In this study, we examine increases and decreases in the total radiation belt electron content (TRBEC) following substorms and geomagnetically quiet intervals. Our results show that the radiation belts are inherently lossy, shown by a negative median change in TRBEC at all intervals following substorms and quiet intervals. However, there are up to 3 times as many increases in TRBEC following substorm intervals. There is a lag of 1-3 days between the substorm or quiet intervals and their greatest effect on radiation belt content, shown in the difference between the occurrence of increases and losses in TRBEC following substorms and quiet intervals, the mean change in TRBEC following substorms or quiet intervals, and the cross correlation between SuperMAG AL (SML) and TRBEC. However, there is a statistically significant effect on the occurrence of increases and decreases in TRBEC up to a lag of 6 days. Increases in radiation belt content show a significant correlation with SML and SYM-H, but decreases in the radiation belt show no apparent link with magnetospheric activity levels.

Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

Co-occurrence of second primary malignancy in patients with thyroid cancer.

BACKGROUND: The discovery of asynchronous or synchronous double or multiple malignancies in patients is not uncommon. The co-occurrence of second primary malignancy (SPM) could be randomly occurring or association with risk factors such as environmental, genetic predisposition and therapy-related. MATERIALS AND METHODS: We retrieved ∼782 million claim records consisting of 10.8 million males and 10.6 million females from Taiwan's National Health Insurance, which were collected for a period of 3 years (January 2000-December 2002). All the patient records were stratified by gender and ages at a 20-year interval with SPMs and specific groups. Interestingness or Q-value was used to measure strength of the disease-disease associations. RESULTS: A total of 9423 thyroid cancer (female: 7483, male: 1940), 276 184 SPM (female: 141 023, male: 135 161) and 861 co-occurrence cases (female: 583, male: 278) were recorded. The co-occurrence incidence rate of head and neck, breast, digestive system and lung was 1.93%, 1.59%, 1.44% and 1.18%, respectively. Malignancy of salivary glands, laryngx, sarcoma, lymphoid tissue, mouth, central nervous system and lungs found Q-value >10. Malignancies with intermediate Q-values (5.0-9.9) were observed in nasopharynx, kidney and ureter, breast, stomach and skin. Prostate, leukemia, urinary bladder, ovary, colon, liver and uterine cervix cancer have lower Q-values (1.0-4.9). CONCLUSION: Co-occurrence ratio of thyroid cancer and SPM was high, occurred in all organ systems. We postulated that the aggressive use of modern diagnostic modalities, aggressive radioiodine treatment, pre-existing molecular oncogen mutations, and thyroid hormone for simultaneously supple-mentary and suppressive therapies were responsible.

Smoking behaviours of adolescents, influenced by smoking of teachers, family and friends.

BACKGROUND: Smoking tobacco is a global health problem, and this study highlights adolescent smoking in Taiwan. Smoking was completely banned on campuses under the Tobacco Hazards Prevention Act and School Health Regulations. Few have investigated the association between personnel smoking/school smoking policies and adolescent smoking in Taiwan. The smoking rate has gradually increased for senior high school students in Taiwan from 10.7% in 1994 to 14.7% in 2011. AIM: This study examined the influence of family and friends' smoking on the association between the presence of teachers smoking and each stage of adolescents' smoking behaviour. METHODS: A cross-sectional survey was conducted in nine high schools (n = 921). Logistic regression analysis was used to examine the association between smoking stage, father smoking, mother smoking, sibling smoking, friends smoking and the presence of smoking teachers. RESULTS: After adjusting for gender, school type and grade, fathers', siblings' and friends' smoking were significantly associated with adolescents' ever and current smoking behaviours, but mothers' smoking was only associated with adolescents' current smoking behaviours. Friends' smoking was strongly associated with being a smoker. While there was an interaction between friends' smoking and the presence of smoking teachers on current smoking behaviours indicating the effect of the presence of smoking teachers was increased when friends did not smoke. DISCUSSION: The results suggest that teachers smoking on school may increase the likelihood of being a current smoker as their friends do not smoke. Family and friends smoking are associated with adolescent smoking. CONCLUSION: The Taiwanese government has regulated a comprehensive smoking ban in schools to prohibit both student and staff smoking on all school premises. To achieve this, schools should make tobacco control communication efforts. Nurses could address the combined influence of family and friends as well as the effect of school smoking restrictions to help prevent adolescents from smoking.

Smoking cessation in Taiwanese male smokers with coronary artery disease: influencing factors and policy implications.

AIM: To investigate factors affecting smoking cessation in male smokers with coronary artery disease. DESIGN: A descriptive, correlation, cross-sectional study was conducted. METHODS: Data were collected using a questionnaire constructed by a literature review of research on smoking cessation in male smokers including demographics and smoking background, as well as psychological, interpersonal and environmental factors. A total of 130 male patients with coronary artery disease were recruited from the cardiac clinic at a regional hospital in Taiwan from August to December 2008. The response rate was 93% (n = 121). Descriptive statistics, chi-square, t-tests and logistic regression analysis were conducted. RESULTS: During the survey, 64.5% of the respondents reported that they had stopped smoking after a coronary event. Five factors were significantly associated with smoking cessation after diagnosis of coronary artery disease: age, the severity of heart diagnoses, antismoking norms (perceived that smoking was against the social norms), nicotine dependence level, and contrary views of smoking (perceived negative expectancy of smoking). Multivariate analysis revealed antismoking norms to be the most important predictor (AOR = 4.27; P < .05) after adjusting age. CONCLUSION: The study highlights the need to develop smoking cessation interventions that specifically counsel patients with coronary artery disease about these information, such as the disease risk and development, health consequences of smoking, and dependence therapy. Additionally, government support for tobacco control programmes in hospitals and elsewhere is designed to have a beneficial effect on patients' smoking behaviours primarily by increasing antismoking norms.

Transporters in the brain endothelial barrier.

The blood-brain barrier (BBB) not only impedes the influx of intravascular substances from blood to brain, but also promotes transport of substances from blood to brain or from brain to blood through several transport systems such as carrier-mediated transport, active efflux transport, and receptor-mediated transport systems. The multidrug resistance transporter P-glycoprotein (P-gp) is an ATP-dependent efflux pump and contributes to efflux of undesirable substances such as amyloid-beta:(Abeta) proteins from the brain into the blood as well as many drugs such as anti-cancer drugs. The inhibition of P-gp has favorable and unfavorable effects on living bodies. P-gp deficiency at the BBB induces the increase of Abeta:deposition in the brain of an Alzheimer disease mouse model. It is also known that the Abeta:deposition is inversely correlated with P-gp expression in the brains of elderly non-demented humans. However, the transient inhibition of P-gp by antidepressants enables medicines such as anti-cancer drugs to enter the brain. Concerning Abeta:clearance in the brain, the low-density lipoprotein receptor-related protein 1 (LRP1) is a major efflux transporter for Abeta, while the receptor for advanced glycation end products (RAGE) is a major influx transporter for Abeta:across the BBB. Dysfunction of the BBB with efflux and influx transporters may contribute to the pathogenesis of some degenerative neuronal disorders. This review will focus on several transporters and discuss how medicines pass the BBB to reach the brain parenchyma.

Lack of association between AKT1 variances versus clinical manifestations and social function in patients with schizophrenia.

The elucidation of genotype-phenotype relationships in psychiatric research is at an early stage. V-akt murine thymoma viral oncogene homolog 1 (AKT1) is a serine/threonine kinase known as protein kinase B. Emerging studies have implicated the role of AKT1 in pathogenesis of schizophrenia; however, the findings have not been consistent. This study aims to examine the association of AKT1 polymorphisms with drug-free and post-treatment symptomatology and social function in patients with schizophrenia. One hundred and twenty newly hospitalised patients with acutely exacerbated schizophrenia who had never been treated by atypical antipsychotics were recruited. They received optimal treatment of risperidone for up to 42 days in the inpatient research unit. Clinical manifestations were monitored by Positive and Negative Syndrome Scale (PANSS) and social function by Nurses' Observation Scale for Inpatients Evaluation (NOSIE). Patients were genotyped for eight AKT1 Single Nucleotide Polymorphism (SNPs), which have been previously investigated for association with schizophrenia. At drug-free status and after best possible treatment of risperidone, genotypes of each SNP did not influence performances in NOSIE, PANSS-total, -positive, -negative and -general psychopathology profiles. These results suggest that AKT1 does not play a significant role in clinical and functional manifestations in patients with schizophrenia who receive risperidone treatment. Future research should also focus on the relationships between genotypes of other susceptibility genes and phenotypes or functional outcomes of schizophrenia.

Calcium signalling and calcium transport in bone disease.

Calcium transport and calcium signalling mechanisms in bone cells have, in many cases, been discovered by study of diseases with disordered bone metabolism. Calcium matrix deposition is driven primarily by phosphate production, and disorders in bone deposition include abnormalities in membrane phosphate transport such as in chondrocalcinosis, and defects in phosphate-producing enzymes such as in hypophosphatasia. Matrix removal is driven by acidification, which dissolves the mineral. Disorders in calcium removal from bone matrix by osteoclasts cause osteopetrosis. On the other hand, although bone is central to management of extracellular calcium, bone is not a major calcium sensing organ, although calcium sensing proteins are expressed in both osteoblasts and osteoclasts. Intracellular calcium signals are involved in secondary control including cellular motility and survival, but the relationship of these findings to specific diseases is not clear. Intracellular calcium signals may regulate the balance of cell survival versus proliferation or anabolic functional response as part of signalling cascades that integrate the response to primary signals via cell stretch, estrogen, tyrosine kinase, and tumor necrosis factor receptors.

MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2.

Motility-related protein-1 (MRP-1/CD9) is involved in cell motility. We studied the change in the actin cytoskeleton, and the expression of actin-related protein (Arp) 2 and Arp3 and the Wiskott-Aldrich syndrome protein (WASP) family according to MRP-1/CD9 gene transduction into HT1080 cells. The frequency of cells with lamellipodia was significantly lower in MRP-1/CD9-transfected HT1080 cells than in control HT1080 cells (P<0.0001). MRP-1/CD9 gene transduction affected the subcellular localization of Arp2 and Arp3 proteins. Furthermore, MRP-1/CD9 gene transduction induced a downregulation of WAVE2 expression (P<0.0001). However, no difference was observed in the expression of Arp2, Arp3 or other WASPs. A neutralizing anti-MRP-1/CD9 monoclonal antibody inhibited downregulation of WAVE2 in MRP-1/CD9-transfected HT1080 cells (P<0.0001), and reversed the morphological effects of MRP-1/CD9 gene transduction. Furthermore, downregulation of WAVE2 by transfection of WAVE2-specific small interfering RNA (siRNA) mimicked the morphological effects of MRP-1/CD9 gene transduction and suppressed cell motility. However, transfection of each siRNA for Wnt1, Wnt2b1 or Wnt5a did not affect WAVE2 expression. Transfection of WAVE2-specific siRNA also did not affect expressions of these Wnts. These results indicate that MRP-1/CD9 regulates the actin cytoskeleton by downregulating of the WAVE2, through the Wnt-independent signal pathway.

Platonin attenuates LPS-induced CAT-2 and CAT-2B induction in stimulated murine macrophages.

BACKGROUND: Platonin, a cyanine photosensitizing dye, is a potent immunomodulator that suppresses acute inflammation. Platonin not only inhibits interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha production but also improves circulatory failure in septic rats. In addition, platonin reduces plasma nitric oxide (NO) formation during sepsis. However, the effects of platonin on inducible NO synthase (iNOS) and cationic amino-acid transporter (including CAT-2, CAT-2 A, and CAT-2B) expressions during sepsis remain uninvestigated. METHODS: Five groups of confluent murine macrophages (RAW264.7 cells) were randomly allocated to receive a 1-h pretreatment of one of five doses of platonin (0.1 microM, 1 microM, 10 microM, 100 microM, or 1000 microM) followed by lipopolysaccharide (LPS; 100 ng ml(-1)). For negative, positive, and platonin control, three other groups of cell cultures were randomly allocated to receive phosphate-buffered saline, LPS, or platonin (1000 microM). The cultures were harvested after exposing them to LPS for 18 h or a comparable duration in those groups without LPS. NO production, L-arginine transport, and expression of the relevant enzymes were then evaluated. RESULTS: Platonin significantly attenuated LPS-induced up-regulation of iNOS expression and NO production in stimulated murine macrophages in a dose-dependent manner. Platonin also significantly inhibited up-regulation of CAT-2 and CAT-2B expression as well as L-arginine transport in LPS-stimulated murine macrophages in a dose-dependent manner. In contrast, CAT-2 A expression in murine macrophages was not affected by LPS and/or platonin. CONCLUSIONS: Platonin attenuates NO production and L-arginine transport in LPS-stimulated murine macrophages possibly through inhibiting iNOS, CAT-2, and CAT-2B expression.

Factors associated with women's and children's body mass indices by income status.

OBJECTIVE: To describe associations between eating behaviors, dietary intake, physical activity, attitudes toward diet and health, sociodemographic variables and body mass index (BMI) among women and children, and differences by household income. DESIGN: Data from the 1994-1996 Continuing Survey of Food Intakes by Individuals (CSFII) and the Diet and Health Knowledge Survey (DHKS) were examined using multivariate regression to estimate the associations between BMI and behavioral and environmental variables among women and children. SUBJECTS: CSFII 1994-1996 is representative of the US population. DHKS surveyed CSFII respondents 20 y of age and over. Our samples consisted of 2419 adult women and 1651 school-age children. MEASUREMENTS: CSFII respondents reported 24 h recalls of all food intakes on 2 nonconsecutive days and their personal and household characteristics, including self-reported height and weight. DHKS collected data on knowledge and attitudes toward dietary guidance and health from CSFII adult respondents. RESULTS: Significant correlations between women's BMI and age, race, dietary patterns, TV watching, and smoking was observed among women from both low- and high-income households. Beverage consumption, eating out, the importance of maintaining healthy weight, and exercise were correlated with BMI only among women from high-income households. Among children, age, race, income, and mother's BMI were significantly correlated with child BMI. CONCLUSIONS: Among women, the associations between some behavioral and environmental factors and BMI differ by household income. Intervention programs need to target specific eating and physical activity behaviors to promote a healthy body weight.

Differential effects of interleukin-6 receptor activation on intracellular signaling and bone resorption by isolated rat osteoclasts.

The effects of the related cytokines interleukin-6 (IL-6), leukemia inhibitory factor (LIF) and oncostatin-M on bone resorption and cytosolic Ca(2+) signaling were compared in isolated rat osteoclasts. In the traditional disaggregated osteoclast (pit) assay, IL-6 and LIF, but not oncostatin-M, conserved the bone resorption otherwise inhibited by high extracellular [Ca(2+)] (15 mM). It produced a paradoxical, concentration-dependent stimulation of resorption by elevated extracellular Ca(2+). In the micro-isolated single osteoclast resorption assay, IL-6, high [Ca(2+)] or IL-6 plus high [Ca(2+)] all increased pit formation. In contrast, the IL-6 receptor (IL-6R)-specific agonist antibody MT-18 inhibited bone resorption in a concentration-dependent manner (1:500 to 1:500 000). MT-18 triggered cytosolic Ca(2+) signals in fura 2-loaded osteoclasts within approximately 10 min of application. Each cytosolic Ca(2+) transient began with a peak deflection that persisted in Ca(2+)-free, EGTA-containing extracellular medium, consistent with a release of intracellularly stored Ca(2+). This was followed by a sustained elevation of cytosolic [Ca(2+)] that was abolished in Ca(2+)-free medium, as expected from an entry of extracellular Ca(2+), and by the Ca(2+) channel antagonist Ni(2+). The inclusion of either IL-6 or soluble human (sh) IL-6R specifically reversed both the above effects of MT-18, confirming that both effects were specific for the IL-6R. The findings suggest that IL-6R activation by IL-6 stimulates osteoclastic bone resorption either by reversing the inhibitory effect of high extracellular Ca(2+) in stromal-containing systems or itself stimulating bone resorption along with Ca(2+) by micro-isolated osteoclasts. In contrast, activation of the IL-6R by an agonist antibody produces an inhibition of bone resorption and an associated triggering of the cytosolic Ca(2+) signals previously associated with regulation of bone resorptive function in other situations.