Cinnamaldehyde attenuates streptozocin-induced diabetic osteoporosis in a rat model by modulating netrin-1/DCC-UNC5B signal transduction.

Background: Cinnamaldehyde (CMD) is a major functional component of Cinnamomum verum and has shown treatment effects against diverse bone diseases. This study aimed to assess the anti-diabetic osteoporosis (DOP) potential of diabetes mellitus (DM) and to explore the underlying mechanism driving the activity of CMD. Methods: A DOP model was induced via an intraperitoneal injection of streptozocin (STZ) into Sprague-Dawley rats, and then two different doses of CMD were administered to the rats. The effects of CMD on the strength, remodeling activity, and histological structure of the bones were assessed. Changes in the netrin-1 related pathways also were detected to elucidate the mechanism of the anti-DOP activity by CMD. Results: CMD had no significant effect on the body weight or blood glucose level of the model rats. However, the data showed that CMD improved the bone strength and bone remodeling activity as well as attenuating the bone structure destruction in the DOP rats in a dose-dependent manner. The expression of netrin-1, DCC, UNC5B, RANKL, and OPG was suppressed, while the expression of TGF-ß1, cathepsin K, TRAP, and RANK was induced by the STZ injection. CMD administration restored the expression of all of these indicators at both the mRNA and protein levels, indicating that the osteoclast activity was inhibited by CMD. Conclusion: The current study demonstrated that CMD effectively attenuated bone impairments associated with DM in a STZ-induced DOP rat model, and the anti-DOP effects of CMD were associated with the modulation of netrin-1/DCC/UNC5B signal transduction.

Effect of off-label targeted drugs on long-term survival in chronic thromboembolic pulmonary hypertension: Insights from a national multicentre prospective registry.

BACKGROUND AND OBJECTIVE: Off-label pulmonary arterial hypertension (PAH)-targeted drugs are commonly prescribed for non-operated chronic thromboembolic pulmonary hypertension (CTEPH), but their effect on the long-term prognosis of CTEPH remains unknown. This study investigated the effect of off-label PAH-targeted drugs on the long-term survival of CTEPH patients. METHODS: CTEPH patients were enrolled from a prospective multicentre national registry. Except for licensed riociguat and treprostinil, other PAH-targeted drugs were off-label. In the original and propensity score-matched (PSM) samples, five-year survival was compared in two groups: (a) patients not receiving off-label PAH-targeted drugs (control) versus (b) patients receiving off-label PAH-targeted drugs (treatment). The latter group was investigated for the effect of started off-label PAH-targeted drugs at baselines (initial) or during follow-up (subsequent). RESULTS: Of 347 enrolled patients, 212 were treated with off-label PAH-targeted drugs initially (n = 173) or subsequently (n = 39), and 135 were untreated. The 1-, 2-, 3- and 5-year survival of the treatment group was significantly higher than that of the control group (97.1% vs. 89.4%, 92.3% vs. 82.1%, 83.2% vs. 75.1% and 71.1% vs. 55.3%, respectively, log-rank test, p = 0.005). Initial treatment was correlated with better 5-year survival after excluding patients with subsequent treatment to reduce the immortal-time bias (hazard ratio: 0.611; 95% CI: 0.397-0.940; p = 0.025). In PSM samples, patients given initial treatment showed significantly better 5-year survival than untreated patients (68.9% vs. 49.3%, log-rank test, p = 0.008). CONCLUSION: Off-label targeted drugs contributed to improved long-term survival in CTEPH patients receiving pharmacotherapies.

Controlled dissolution of a single ion from a salt interface.

Interactions between monatomic ions and water molecules are fundamental to understanding the hydration of complex polyatomic ions and ionic process. Among the simplest and well-established ion-related reactions is dissolution of salt in water, which is an endothermic process requiring an increase in entropy. Extensive efforts have been made to date; however, most studies at single-ion level have been limited to theoretical approaches. Here, we demonstrate the salt dissolution process by manipulating a single water molecule at an under-coordinated site of a sodium chloride film. Manipulation of molecule in a controlled manner enables us to understand ion-water interaction as well as dynamics of water molecules at NaCl interfaces, which are responsible for the selective dissolution of anions. The water dipole polarizes the anion in the NaCl ionic crystal, resulting in strong anion-water interaction and weakening of the ionic bonds. Our results provide insights into a simple but important elementary step of the single-ion chemistry, which may be useful in ion-related sciences and technologies.

Clinical features and long-term survival in idiopathic pulmonary arterial hypertension with thyroid dysfunction: insights from a national multicentre prospective study.

Background: Our objective was to clarify the characteristics and long-term survival of idiopathic pulmonary arterial hypertension (IPAH) patients with thyroid dysfunction and compare them with IPAH without thyroid dysfunction. Methods: A retrospective analysis was conducted using prospectively collected data. IPAH patients with thyroid dysfunction at baseline were included. Patients with other subgroups of PAH and Group 2-5 pulmonary hypertension were excluded. IPAH patients with euthyroid function were matched 1:1 to IPAH patients with thyroid dysfunction by age and sex. Results: In total, 148 IPAH patients with thyroid dysfunction were included. Patients with hyperthyroidism, hypothyroidism, subclinical hyperthyroidism and subclinical hypothyroidism accounted for 16.2%, 18.9%, 8.1% and 56.8%, respectively. IPAH patients with hyperthyroidism showed the highest mixed venous oxygen saturation (SvO2) and the lowest pulmonary vascular resistance (PVR) at baseline among subgroups, while patients with subclinical hypothyroidism had the lowest SvO2 and highest PVR (p<0.05). Compared with IPAH without thyroid dysfunction, patients with hyperthyroidism (9.14 versus 13.86 WU; p<0.05) and hypothyroidism (10.70 versus 13.86 WU; p<0.05) showed significantly lower PVR. The haemodynamic profiles of patients with subclinical hypothyroidism were similar to IPAH with euthyroid function except for lower right atrial pressure (6 versus 8 mmHg; p=0.009). The long-term survival of patients with clinical thyroid dysfunction was better than IPAH without thyroid dysfunction, while that of those with subclinical diseases was comparable to the latter, even after adjusting for baseline haemodynamics and treatment. Conclusion: IPAH patients with clinical hyper- and hypothyroidism had better haemodynamics and survival than those without thyroid dysfunction, while patients with subclinical hypothyroidism had similar haemodynamics and survival profiles to the latter.

10-year survival of pulmonary arterial hypertension associated with connective tissue disease: insights from a multicentre PAH registry.

OBJECTIVES: To report the 10-year survival rate and prognostic factors of pulmonary arterial hypertension associated with CTD (CTD-PAH) patients, to compare treatment and survival between patients enrolled before and after 2015, and to validate the discrimination of the recommended four-strata model in predicting 10-year survival at follow-up in Chinese CTD-PAH patients. METHODS: This study was derived from a Chinese national multicentre prospective registry study from 2009 to 2019. Medical records were collected at baseline and follow-up, including PAH-targeted therapy and binary therapy (both CTD and PAH-targeted therapy). RESULTS: A total of 266 CTD-PAH patients were enrolled and the 10-year survival rate was 59.9% (median follow-up time: 4.85 years). Underlying CTD (SSc), baseline 6-min walking distance and SaO2 were independent risk factors for 10-year survival. The proportion of patients receiving PAH-targeted combination therapy increased from 10.1% (2009-2014) to 26.5% (2015-2019) and that of binary therapy increased from 14.8% to 35%. The 1-year survival rate increased from 89.8% (2009-2014) to 93.9%, and the 3-year survival rate increased from 80.1% (2009-2014) to 86.5% (both P > 0.05). The four-strata strategy performed well in predicting 10-year survival at follow-up (C-index = 0.742). CONCLUSION: The 10-year survival rate of CTD-PAH patients was reported for the first time. The 10-year prognosis was poor, but there was a tendency for more standardized treatment and better survival in patients enrolled after 2015. The recommended four-strata model at follow-up can effectively predict 10-year survival in CTD-PAH patients.

Characteristics, treatments and survival of pulmonary arterial hypertension associated with congenital heart disease in China: Insights from a national multicenter prospective registry.

BACKGROUND: The purpose of this registry was to provide insights into the characteristics, treatments and survival of patients with PAH-CHD in China. METHODS: Patients diagnosed with PAH-CHD were enrolled in this national multicenter prospective registry. Baseline and follow-up data on clinical characteristics, PAH-targeted treatments and survival were collected. RESULTS: A total of 1060 PAH-CHD patients (mean age 31 years; 67.9% females) were included, with Eisenmenger syndrome (51.5%) being the most common form and atrial septal defects (37.3%) comprising the most frequent underlying defect. Approximately 33.0% of the patients were in World Health Organization functional class III to IV. The overall mean pulmonary arterial pressure and pulmonary vascular resistance were 67.1 (20.1) mm Hg and 1112.4 (705.9) dyn/s/cm5, respectively. PAH-targeted therapy was utilized in 826 patients (77.9%), and 203 patients (19.1%) received combination therapy. The estimated 1-, 3-, 5-, and 10-year survival rates of the overall cohort were 96.9%, 92.9%, 87.6% and 73.0%, respectively. Patients received combination therapy had significantly better survival than those with monotherapy (p = 0.016). NT-proBNP >1400 pg/ml, SvO2 ≤ 65% and Borg dyspnea index ≥ 3 and PAH-targeted therapy were independent predictors of mortality. Hemoglobin > 160g/L was a unique predictor for mortality in Eisenmenger syndrome. CONCLUSIONS: Chinese PAH-CHD patients predominantly exhibit Eisenmenger syndrome and have significantly impaired exercise tolerance and right ventricular function at diagnosis, which are closely associated with long-term survival. PAH-targeted therapy including combination therapy showed a favorable effect on survival in PAH-CHD. The long-term survival of Chinese CHD-PAH patients remains to be improved.

A Nomogram for Predicting 3-Year Mortality in Patients with Pulmonary Hypertension due to Left Heart Failure: A Retrospective Analysis of a Prospective Registry Study.

INTRODUCTION: Pulmonary hypertension due to left heart failure (PH-LHF) is a disease with high prevalence and 3-year mortality rates. Consequently, timely identification of patients with high mortality risk is critical. This study aimed to build a nomogram for predicting 3-year mortality and screening high-risk PH-LHF patients. METHODS: This nomogram was developed on a training cohort of 175 patients with PH-LHF diagnosed by right heart catheterization. Multivariate Cox regression was used to identify independent predictors and develop this nomogram. The median total points obtained from the nomogram were used as a cutoff point, and patients were classified into low- and high-risk groups. The concordance index (C-index) and calibration curve were utilized to ascertain the predictive accuracy and discriminative ability of the nomogram. External validation was performed using a validation cohort of 77 PH-LHF patients from other centers. RESULTS: Multivariate Cox regression showed that the New York Heart Association Functional classification (NYHA FC), uric acid level, and mean pulmonary arterial pressure were all independent predictors and incorporated into the nomogram. The nomogram showed good discrimination (C-index of 0.756; 95% CI: 0.688-0.854) and good calibration. The Kaplan-Meier survival analysis showed that patients in the high-risk group had worse survival (p < 0.001). In the external validation, the nomogram showed both good discrimination (C-index of 0.738; 95% CI: 0.591-0.846) and calibration. CONCLUSION: The nomogram had a good performance in predicting 3-year mortality and can effectively identify high-risk patients. The nomogram may help to reduce the mortality of PH-LHF.

Characteristics, Long-term Survival, and Risk Assessment of Pediatric Pulmonary Arterial Hypertension in China: Insights From a National Multicenter Prospective Registry.

BACKGROUND: Registry-based studies of pediatric pulmonary arterial hypertension (PPAH) are scarce in developing countries, including China. The PPAH risk assessment tool needs further evaluation and improvement. RESEARCH QUESTION: What are the characteristics and long-term survival of PPAH in China and what is the performance of the PPAH risk model in Chinese patients? STUDY DESIGN AND METHODS: Patients with PAH were enrolled in the national prospective multicenter registry from August 2009 through December 2019. Children 3 months to 18 years of age at the time of PAH diagnosis were analyzed. RESULTS: A total of 247 children with PAH were enrolled. The median patient age was 14.8 years, and 58.3% of patients were female. Most patients had a diagnosis of PAH associated with congenital heart disease (CHD; 61.5%) and idiopathic or heritable PAH (37.7%). The median time from symptom onset to PAH diagnosis was 24 months. The mean pulmonary artery pressure and pulmonary vascular resistance index were 70.78 ± 19.80 mm Hg and 21.82 ± 11.18 Wood Units·m2, respectively. Patients with CHD-associated PAH experienced a longer diagnostic delay and demonstrated higher pulmonary artery pressure, but better cardiac performance, than those with idiopathic or heritable PAH. An increased number of patients received targeted therapy at the last follow-up compared with baseline. The 5- and 10-year survival rates of the entire cohort were 74.9% and 55.7%, respectively, with better survival in patients with CHD-associated PAH than in those with idiopathic or heritable PAH. Patients with low risk had better survival than those with high risk according to the simplified noninvasive risk score model with weight, function class, and echocardiographic right ventricular size, both at baseline and follow-up. INTERPRETATION: Patients with PPAH in China showed severely compromised hemodynamics with marked diagnostic delay. The long-term survival of PPAH is poor despite the increased usefulness of targeted drugs. The simplified noninvasive risk model demonstrated good performance for predicting survival in Chinese children with PAH. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01417338; URL: www. CLINICALTRIALS: gov.

Decoupling of CVD-grown epitaxial graphene using NaCl intercalation.

The structural and electronic properties of graphene grown on catalytic metal surfaces are significantly modified via graphene-substrate interaction. To minimize the influence of the metal substrate, a dielectric buffer layer can be introduced between the graphene and metal substrate. However, the catalytic synthesis of graphene limits the potential alternatives for buffer layers. The intercalation of atoms below the graphene layer is a promising method that does not require the chemical treatment of graphene or the substrate. In this study, the electronic and structural properties of single-layer graphene (SLG) on the Cu(111) substrate intercalated with ultrathin NaCl thin films were investigated using scanning tunnelling microscopy. The intercalation of the NaCl monolayer decoupled SLG from the metal substrate, thereby producing quasi-freestanding graphene.

The prevalence and survival of pulmonary hypertension due to left heart failure: A retrospective analysis of a multicenter prospective cohort study.

Background: Pulmonary hypertension due to left heart failure (PH-LHF) is currently the most common form of pulmonary hypertension (PH) encountered in clinical practice. Despite significant advances that have improved our understanding of PH-LHF over the past two decades, the mortality is still high in recent decades. This study aimed to describe the prevalence and survival of patients with PH-LHF, and explored the potential risk factors which may predict the prognosis of PH-LHF. Methods: A retrospective analysis of a prospective cohort study of left heart failure (LHF) patients who underwent right heart catheterization (RHC) between January 2013 and November 2016 was performed. The endpoint was all-cause mortality. Follow-ups were performed every 6 months ± 2 weeks. Results: A total of 480 patients with LHF were enrolled, with 215 (44.8%) having PH-LHF. The proportion of PH-LHF was significantly lower in coronary artery disease (CAD) group than without CAD (41.3 vs. 57.8%, p = 0.003). However, multivariable logistic regression analysis revealed that CAD was not associated with PH-LHF (Adjusted OR: 1.055, 95% CI: 0.576 - 1.935, p = 0.862). 75 of 215 (34.9%) patients with PH-LHF died during a median follow-up period of 84.6 months. The 1-, 3-, 5-, and 8-year survival rates of all PH-LHF patients were 94.3, 76.9, 65.8, and 60.2%, respectively. New York Heart Association Functional Class (NYHA FC), hemoglobin, and systolic pulmonary artery pressure (sPAP) were associated with mortality of PH-LHF in multivariate Cox analysis. Conclusion: PH is commonly identified in patients with LHF, with a prevalence of approximately 45%. The mortality is still high in patients with PH-LHF. NYHA FC, hemoglobin, and sPAP are independent risk predictors of mortality for PH-LHF. These findings may be useful for risk stratification in future clinical trial enrollment.

Impact of borderline pulmonary hypertension due to left heart failure on mortality in a multicenter registry study: A 3-year survivorship analysis.

Background: Patients with left heart failure (LHF) are often associated with the development of pulmonary hypertension (PH) which leads to an increased risk of death. Recently, the diagnostic standard for PH has changed from mean pulmonary arterial pressure (mPAP) ≥25 mmHg to >20 mmHg. Nonetheless, the effect of borderline PH (mPAP: 21-24 mmHg) on the prognosis of LHF patients is unclear. This study aimed to investigate the relationship between borderline PH and 3-year clinical outcomes in LHF patients. Methods: A retrospective analysis of a prospective cohort study was done for LHF patients who underwent right heart catheterization (RHC) between January 2013 and November 2016. The primary outcome was all-cause mortality; the secondary outcome was rehospitalization. Results: Among 344 patients, 62.5% were identified with a proportion of PH (mPAP ≥ 25), 10.8% with borderline PH (21-24), and 26.7% with non-PH (≤20), respectively. Multivariable Cox analysis revealed that borderline PH patients had a higher adjusted mortality risk (HR = 3.822; 95% CI: 1.043-13.999; p = 0.043) than non-PH patients. When mPAP was treated as a continuous variable, the hazard ratio for death increased progressively with increasing mPAP starting at 20 mmHg (HR = 1.006; 95% CI: 1.001-1.012). There was no statistically significant difference in adjusted rehospitalization between borderline PH and non-PH patients (HR = 1.599; 95% CI: 0.833-3.067; p = 0.158). Conclusions: Borderline PH is independently related to increased 3-year mortality in LHF patients. Future research is needed to evaluate whether more close monitoring, and managing with an intensifier improves clinical outcomes in borderline PH caused by LHF. Clinical trials registration: www.clinicaltrials.gov NCT02164526.

Prediabetes and osteoporotic fracture risk: A meta-analysis of prospective cohort studies.

BACKGROUND: Diabetes confers an increased risk of fracture. However, whether prediabetes is also a risk factor of osteoporotic fracture has not been comprehensively examined. We performed a meta-analysis to evaluate the relationship between prediabetes and osteoporotic fracture risk. METHODS: This meta-analysis included relevant prospective cohort studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intra-study heterogeneity was selected to pool the results. Subgroup analyses were applied to evaluate the influences of study characteristics on relationship between prediabetes and osteoporotic fracture risk. RESULTS: Eight studies including 33,136 community dwelling adult patients were included, and 7429 (22.4%) patients were prediabetic. Prediabetes was not independently associated with a higher risk of osteoporotic fracture compared with normoglycemia (adjusted risk ratio: 1.03, 95% confidence interval: 0.88-1.21, P = 0.69, I2  = 42%). Sensitivity limited to the elderly population showed consistent results (RR: 1.10, 95% CI: 0.91-1.24, P = 0.15, I2  = 0%). Subgroup analysis suggested that prediabetes defined by HbA1c (approximately 5.7%-6.4%) was associated with a higher risk of osteoporotic fracture (RR: 1.24, 95% CI: 1.01-1.53, P = 0.04), but not that defined by impaired fasting glucose or impaired glucose tolerance (P = 0.60). Sex, follow-up duration, and adjustment of bone mineral density did not significantly affect the outcome. CONCLUSIONS: Current evidence does not support that prediabetes is independently associated with osteoporotic fracture risk. Different definitions of prediabetes may affect the association between prediabetes and osteoporotic fracture risk.

Adlayer-Free Large-Area Single Crystal Graphene Grown on a Cu(111) Foil.

To date, thousands of publications have reported chemical vapor deposition growth of "single layer" graphene, but none of them has described truly single layer graphene over large area because a fraction of the area has adlayers. It is found that the amount of subsurface carbon (leading to additional nuclei) in Cu foils directly correlates with the extent of adlayer growth. Annealing in hydrogen gas atmosphere depletes the subsurface carbon in the Cu foil. Adlayer-free single crystal and polycrystalline single layer graphene films are grown on Cu(111) and polycrystalline Cu foils containing no subsurface carbon, respectively. This single crystal graphene contains parallel, centimeter-long ≈100 nm wide "folds," separated by 20 to 50 µm, while folds (and wrinkles) are distributed quasi-randomly in the polycrystalline graphene film. High-performance field-effect transistors are readily fabricated in the large regions between adjacent parallel folds in the adlayer-free single crystal graphene film.

Monitoring and evaluating the adherence to a complementary food supplement (Ying Yang Bao) among young children in rural Qinghai, China: a mixed methods evaluation study.

BACKGROUND: Large investments are currently made in community-based complementary food supplement (Ying Yang Bao, YYB) programs to improve nutrition of young children in rural areas in China. However, there is a lack of knowledge about the experience and challenges of implementing YYB programs in China. We aimed to: 1) monitor distribution of YYB; 2) assess children's adherence to and acceptability of YYB; and 3) evaluate community-based strategies to improve the program. METHODS: This mixed methods evaluation study combined data from surveys and focus groups that took place during a controlled interventional evaluation trial. The trial aimed to evaluate the effectiveness of community-based YYB distribution on improving children's health status in rural areas in China. We conducted five cross-sectional surveys with caregivers of children aged 6-23 months (baseline survey (N = 1804) in August 2012 and four follow-up cross-sectional surveys: 1) N = 494 in January 2013; 2) N = 2187 in August 2013; 3) N = 504 in January 2014; and 4) N = 2186 in August 2014) in one rural county in Qinghai Province. We used a two-stage cluster sampling technique to select mothers with eligible children for each survey. Information was collected from caregivers on household characteristics, YYB consumption and acceptability in the surveys. High adherence in each survey was defined as children who consumed at least four YYB sachets during the previous week. A logistic regression model was developed to obtain odds ratios (OR) with 95% confidence intervals of factors associated with high adherence. Also, we conducted 10 focus groups with73 caregivers and health workers involved in the YYB distribution. Content analysis was used to explore qualitative findings, which were used to gain deeper insight into the quantitative results. RESULTS: Around 90% of caregivers had ever received YYB and more than 80% of children ever took YYB. Caregivers mainly knew about YYB through their village doctors. High adherence to YYB increased from 49.4% in the first follow-up survey (January 2013) to 81.4% in the last follow-up survey (August 2014; P < 0.0001). Repeated training sessions with village doctors could increase adherence. However, due to unplanned YYB stock-out, caregivers did not receive YYB for six months, which may have led to a decrease of high adherence from 64.1% in the second follow-up survey (August 2013) to 53.6% in the third follow-up survey (January 2014; P < 0.0001). Self-reported acceptability increased from 43.2% to 71.8%, partly due to improving the taste of YYB, which was the main reason that children disliked taking YYB. Unfortunately, more than 60% of caregivers did not perceive positive health improvement in their children after taking YYB. Multivariate analysis showed that children with diarrhea (OR = 1.216, 95% CI 1.025-1.442), cough or fever (OR = 1.222, 95% CI 1.072-1.393) during the past two weeks had significantly lower adherence. CONCLUSIONS: This evaluation study showed that program monitoring in rural West China was critically important for understanding program implementation and adherence trends. This led to strategic changes to the intervention over time: improving the taste of YYB; strengthening health education of village doctors and caregivers; and ensuring continuity of YYB supply. Future programs need to monitor program implementation in other settings in China and elsewhere.

Effectiveness of complementary food supplements and dietary counselling on anaemia and stunting in children aged 6-23 months in poor areas of Qinghai Province, China: a controlled interventional study.

OBJECTIVE: To assess the effectiveness of dietary counselling and complementary food supplements on anaemia and stunting prevalence in children aged 6-23 months. DESIGN: A controlled intervention study with measurements of height and haemoglobin levels, and cross-sectional surveys in August 2012 (baseline), 2013 (mid-term) and 2014 (end-line). SETTING: One intervention county and one control county in rural Qinghai Province, China. INTERVENTION: Complementary food supplements (containing protein, fat, carbohydrate, vitamin A, B1, B2, B12, D3, folic acid, iron, zinc and calcium) and complementary feeding counselling were given in the intervention county. PARTICIPANTS: Caregivers and their children aged 6-23 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Effect of the interventions on the prevalence of anaemia (haemoglobin <110 g/L) and stunting (z-score of height-for-age <-2.0) (controlled for differences between the counties), and on infant feeding practices. RESULTS: The surveys were conducted on 1804, 2187 and 2186 children aged 6-23 months in the intervention county in August 2012, 2013 and 2014, respectively, and 804, 680 and 790 children in the control county, respectively. Between the baseline and end-line surveys, anaemia prevalence decreased more in the intervention county than in the control county (71.1% to 47.8% vs 86.3% to 75.3%, respectively; p<0.0001). There was no difference in the decrease in stunting prevalence between the counties (9.7% to 7.1% vs 17.0% to 15.0%; p=0.7954). The proportions of children given iron-rich or iron-fortified food, introduced to (semi-) solid food at 6-8 months, and given food with minimum dietary diversity increased from 43.2% to 88.8% (p<0.0001), 81.4% to 96% (p=0.0470) and 53.0% to 59.8% (p<0.0001), respectively in the intervention county. CONCLUSIONS: We found much higher anaemia prevalence in poor rural areas of Qinghai Province compared with the national data. Community-based complementary food supplements combined with dietary counselling can improve feeding practices and reduce anaemia prevalence. Future studies should use longer follow-up to assess the effects on stunting. STRENGTHS AND LIMITATIONS: We included a large number of participants and assessed a combined complementary food supplements and dietary counselling intervention in a poor rural area in China with high anaemia prevalence. Although the study took place in only one intervention county and one control county, we conducted an analysis that controlled for differences between the two counties. Also, although we made significant efforts to train village doctors, their education was not systematically assessed after training and thus their delivery of the interventions may have been variable. TRIAL REGISTRATION NUMBER: ChiCTRPRC12002444; Pre-results.

Sleep quality and cognitive decline in a community of older adults in Daqing City, China.

OBJECTIVES: To examine the association between self-reported sleep quality and cognitive decline one year later. PATIENTS/METHODS: A longitudinal study of 1010 cognitively intact adults, aged 65-80 years at baseline, from two urban communities in China was performed. Sleep quality at baseline was measured using the Pittsburgh Sleep Quality Index (PSQI). Cognitive function was determined by using the Chinese version of Mini-Mental State Examination (CMMSE) at the baseline and one year later. Substantial CMMSE decline was defined as the CMMSE score decreases by three or more points during the follow-up. Potential confounders, such as age, sex, education, baseline CMMSE score, depression, physical activity level, drinking status, smoking status, body mass index, snoring frequency, history of hypertension, diabetes, and coronary heart disease were measured via questionnaires or physical examination. RESULTS: After adjusting for potential confounders, individuals with poor sleep quality (PSQI > 7), relative to whose with good sleep quality, had 0.32 (95% CI: -0.62, -0.02; p = 0.04) CMMSE-points more decline and tended to have a higher likelihood of developing substantial CMMSE decline (OR = 1.46; 95% CI: 0.97, 2.18; p = 0.06). Among seven subscales of the PSQI, poor sleep efficiency was associated with greater CMMSE decline (beta = -0.16, 95% CI: -0.29, -0.03; p = 0.01) and higher risk of substantial CMMSE decline (OR = 1.24, 95% CI: 1.05, 1.46; p = 0.01). Short sleep duration (sleeping ≤5 h/night) was also significantly associated with more CMMSE decline and a higher likelihood of developing substantial CMMSE decline (p <0.05 for both). CONCLUSIONS: Self-reported poor sleep quality may be an indicator of early cognitive decline for elderly people and should be paid particular attention by clinicians.

Moderate-intensity exercise improves the thromboelastography coagulation index in children with severe hemophilia A.

This pilot study explored the effect of moderate-intensity exercise on factor VIII (FVIII) activity and global hemostatic status of the children with severe hemophilia A. Eleven children aged 6 to 15 years with severe hemophilia A participated in a moderate-intensity exercise test by using Recumbent Cross Trainer (NuStep, T5XR) for at least 10 min after reaching the target heart rate or until volitional exhaustion within a safety framework. Blood samples were collected pre and postexercise for plasma FVIII: C and thromboelastography (TEG) parameters and coagulation index. The average duration of exercise was 11.8 min (10-13 min). There was no report on bleeding events or adverse symptoms requiring termination of the exercise test. The average FVIII activity of the 11 children was 0.66 (0.5-0.8) IU/dl before and 0.93 (0.5-2.3) IU/dl after exercise. The increase of FVIII in the 11 children as a group was not statistically significant (P = 0.052). There were significant changes of TEG measurements, with shortening of R (P < 0.05), and increase in K decrease (P < 0.05), alpha angle (P < 0.05), maximum amplitude (P < 0.05), and coagulation index (P < 0.01). Among the 11 children, the relative coagulation index increase after exercise was greater than 50% in seven (63.6%), less than 20% in three (27.3%), and less than 10% in one (9.1%). TEG analysis showed that the global hemostatic function for the children with severe hemophilia A can be enhanced after moderate-intensity exercise.

Iron, oxidative stress and gestational diabetes.

Both iron deficiency and hyperglycemia are highly prevalent globally for pregnant women. Iron supplementation is recommended during pregnancy to control iron deficiency. The purposes of the review are to assess the oxidative effects of iron supplementation and the potential relationship between iron nutrition and gestational diabetes. High doses of iron (~relative to 60 mg or more daily for adult humans) can induce lipid peroxidation in vitro and in animal studies. Pharmaceutical doses of iron supplements (e.g., 10× RDA or more for oral supplements or direct iron supplementation via injection or addition to the cell culture medium) for a short or long duration will induce DNA damage. Higher heme-iron intake or iron status measured by various biomarkers, especially serum ferritin, might contribute to greater risk of gestational diabetes, which may be mediated by iron oxidative stress though lipid oxidation and/or DNA damage. However, information is lacking about the effect of low dose iron supplementation (≤ 60 mg daily) on lipid peroxidation, DNA damage and gestational diabetes. Randomized trials of low-dose iron supplementation (≤ 60 mg daily) for pregnant women are warranted to test the relationship between iron oxidative stress and insulin resistance/gestational diabetes, especially for iron-replete women.

Increasing trends in Schedule II opioid use and doctor shopping during 1999-2007 in California.

PURPOSE: To examine the age and gender-specific trends of Schedule II opioid use among California residents, with special reference to multiple provider users (doctor shoppers). METHODS: Utilizing data from the California Prescription Drug Monitoring Program, we examined age and gender-specific trends of Schedule II opioid use during calendar years 1999-2007. Specifically, we analyzed the following: (1) the prevalence of Schedule II opioid users among California's population and (2) the proportion of these opioid users who were doctor shoppers (defined as an individual who used more than five different prescribers for all Schedule II opioids he or she obtained in a calendar year). RESULTS: Among all age and gender groups, the prevalence of Schedule II opioid users in California increased by 150%-280% and the prevalence of doctor shoppers among users increased by 111%-213% over 9 years. The prevalence of opioid users was lowest among 18-44 year old men (1.25%) and highest among 65-year and older women (5.31%) by 2007. The prevalence of doctor shoppers was approximately 1.4% among those up to age 64 years and 0.5% among those 65 years and older. The gender difference in doctor shoppers among all age groups was negligible. On average, the cumulative morphine-equivalent amount of Schedule II opioid per individual obtained per year was threefold to sixfold higher for doctor shoppers than for the general population across different age and gender groups. CONCLUSIONS: Age and gender differences in opioid use were relatively small, whereas the trends for use of opioids and multiple providers grew at a disquieting rate.

Age, gender, and earlier opioid requirement associations with the rate of dose escalation in long-term opioid therapy.

OBJECTIVES: To examine the association of risk factors, age, gender, and earlier opioid requirement with the rate of dose escalation in long-term opioid therapy. METHODS: This is a retrospective cohort study of 1,922 individuals identified from California's prescription drug monitoring program database who continuously used opioids from 1999 to 2007. A linear mixed-effects model was used to examine the association of age, gender, and baseline dose requirement with the rate of subsequent opioid dose change. Because of different reporting requirements before and after January 1, 2005, the analyses were conducted separately for patients' opioid use in two periods (6 years between 1999 and 2004 and 3 years between 2005 and 2007). RESULTS: Both the 6-year and the 3-year data showed a significant age association, with younger patients having a higher rate of dose escalation than older patients (p = 0.021 and <0.0001, respectively). Females had a lower rate of dose escalation than males, although the result did not achieve statistical significance in the 6-year data (p = 0.165 and 0.013, respectively). The higher the dose requirement a patient had at baseline, the lower the rate of dose escalation (p < 0.0001 in both periods). CONCLUSIONS: Age, gender, and earlier dose requirement were associated with the rate of dose change in 9-year long-term opioid therapy. Patients aged 75-100 years, being female or having large dose requirement at an earlier stage of therapy may experience a slower dose escalation or even dose decline.