Comparing the relationship between stature and later life health in six low and middle income countries

This paper examines the relationship between stature and later life health in 6 emerging economies, each of which are expected to experience significant increases in the mean age of their populations over the coming decades. Using data from the WHO Study on Global Ageing and Adult Health (SAGE) and pilot data from the Longitudinal Ageing Study in India (LASI), I show that various measures of health are associated with height, a commonly used proxy for childhood environment. In the pooled sample, a 10 cm increase in height is associated with between a 2 and 3 percentage point increase in the probability of being in very good or good self-reported health, a 3 percentage point increase in the probability of reporting no difficulties with activities of daily living or instrumental activities of daily living, and between a fifth and a quarter of a standard deviation increase in grip strength and lung function. Adopting a methodology previously used in the research on inequality, I also summarise the height-grip strength gradient for each country using the concentration index, and provide a decomposition analysis.

Acute Cocoa Supplementation Increases Postprandial HDL Cholesterol and Insulin in Obese Adults with Type 2 Diabetes after Consumption of a High-Fat Breakfast

BACKGROUND: Dietary cocoa is an important source of flavonoids and is associated with favorable cardiovascular disease effects, such as improvements in vascular function and lipid profiles, in nondiabetic adults. Type 2 diabetes (T2D) is associated with adverse effects on postprandial serum glucose, lipids, inflammation, and vascular function.

OBJECTIVE: We examined the hypothesis that cocoa reduces metabolic stress in obese T2D adults after a high-fat fast-food-style meal.

METHODS: Adults with T2D [n = 18; age (means ± SEs): 56 ± 3 y; BMI (in kg/m(2)): 35.3 ± 2.0; 14 women; 4 men) were randomly assigned to receive cocoa beverage (960 mg total polyphenols; 480 mg flavanols) or flavanol-free placebo (110 mg total polyphenols; <0.1 mg flavanols) with a high-fat fast-food-style breakfast [766 kcal, 50 g fat (59% energy)] in a crossover trial. After an overnight fast (10-12 h), participants consumed the breakfast with cocoa or placebo, and blood sample collection [glucose, insulin, lipids, and high-sensitivity C-reactive protein (hsCRP)] and vascular measurements were conducted at 0.5, 1, 2, 4, and 6 h postprandially on each study day. Insulin resistance was evaluated by homeostasis model assessment.

RESULTS: Over the 6-h study, and specifically at 1 and 4 h, cocoa increased HDL cholesterol vs. placebo (overall Δ: 1.5 ± 0.8 mg/dL; P ≤ 0.01) but had no effect on total and LDL cholesterol, triglycerides, glucose, and hsCRP. Cocoa increased serum insulin concentrations overall (Δ: 5.2 ± 3.2 mU/L; P < 0.05) and specifically at 4 h but had no overall effects on insulin resistance (except at 4 h, P < 0.05), systolic or diastolic blood pressure, or small artery elasticity. However, large artery elasticity was overall lower after cocoa vs. placebo (Δ: -1.6 ± 0.7 mL/mm Hg; P < 0.05), with the difference significant only at 2 h.

CONCLUSION: Acute cocoa supplementation showed no clear overall benefit in T2D patients after a high-fat fast-food-style meal challenge. Although HDL cholesterol and insulin remained higher throughout the 6-h postprandial period, an overall decrease in large artery elasticity was found after cocoa consumption. This trial was registered at clinicaltrials.gov as NCT01886989.

LYRIC/AEG-1 is targeted to different subcellular compartments by ubiquitinylation and intrinsic nuclear localization signals

PURPOSE: LYRIC/AEG-1 has been reported to influence breast cancer survival and metastases, and its altered expression has been found in a number of cancers. The cellular function of LYRIC/AEG-1 has previously been related to its subcellular distribution in cell lines. LYRIC/AEG-1 contains three uncharacterized nuclear localization signals (NLS), which may regulate its distribution and, ultimately, function in cells.

EXPERIMENTAL DESIGN: Immunohistochemistry of a human prostate tissue microarray composed of 179 prostate cancer and 24 benign samples was used to assess LYRIC/AEG-1 distribution. Green fluorescent protein-NLS fusion proteins and deletion constructs were used to show the ability of LYRIC/AEG-1 NLS to target green fluorescent protein from the cytoplasm to the nucleus. Immunoprecipitation and Western blotting were used to show posttranslational modification of LYRIC/AEG-1 NLS regions.

RESULTS: Using a prostate tissue microarray, significant changes in the distribution of LYRIC/AEG-1 were observed in prostate cancer as an increased cytoplasmic distribution in tumors compared with benign tissue. These differences were most marked in high grade and aggressive prostate cancers and were associated with decreased survival. The COOH-terminal extended NLS-3 (amino acids 546-582) is the predominant regulator of nuclear localization, whereas extended NLS-1 (amino acids 78-130) regulates its nucleolar localization. Within the extended NLS-2 region (amino acids 415-486), LYRIC/AEG-1 can be modified by ubiquitin almost exclusively within the cytoplasm.

CONCLUSIONS: Changes in LYRIC/AEG-1 subcellular distribution can predict Gleason grade and survival. Two lysine-rich regions (NLS-1 and NLS-3) can target LYRIC/AEG-1 to subcellular compartments whereas NLS-2 is modified by ubiquitin in the cytoplasm.

Chronic PEGylated obestatin treatment prevents the onset of high fat diet-induced hypertension and endothelial dysfunction in the absence of metabolic actions

Background: Obestatin is a gastrointestinal peptide with established metabolic actions and emerging vascular effects which involve activation of NO signalling. The aim of this study was to investigate effects of a recently-characterised stable analogue, PEGylated obestatin (PEG-OB), in the setting of diet-induced obesity which is associated with both metabolic and vascular dysfunction. Methods: Male Sprague Dawley rats (6 weeks; n=8) were maintained on standard (SD) or high fat (HF) diet (60% fat) for 8 weeks with once-daily injection of either PEG-OB (50nmol/kg/day) or saline from 2 weeks. Results: HF feeding for 8 weeks resulted in marked body weight gain which was not affected by chronic PEG-OB treatment (HF saline, 175.0±12.2; HF PEG-OB, 190.4±6.4g; P=NS). Similarly, blood glucose, as indicated by HbA1c (HF saline, 6.30±0.15; HF PEG-OB, 6.13±0.36%; P=NS) and insulin tolerance (HF saline, 105.2±52.5; HF PEG-OB, 90.3±45.4mmol/L.min; P=NS), were unaltered by PEG-OB. Despite the apparent lack of metabolic effects, chronic PEG-OB treatment markedly attenuated development of HF-induced hypertension (HF saline, 146.5±4.9mmHg; HF PEG-OB, 123.0±9.7mmHg; P<0.01), assessed by tail-cuff plethysmography. Furthermore, organ bath pharmacology in isolated aortic rings, indicated that HF diet-induced endothelial dysfunction was completely prevented by PEG-OB (acetylcholine, EC50: SD saline, 335±113; HF saline, 758±164; HF PEG-OB, 277±85nmol/L; P<0.05). However, contraction to phenylephrine and relaxation to the NO donor, sodium nitroprusside, were unaltered between groups. Conclusions: PEG-OB exerts beneficial effects on hypertension and endothelial function in diabetes independently of metabolic actions suggesting that obestatin signalling may represent a novel therapeutic target to reduce the risk of associated cardiovascular complications.

Ocular comorbidities among cataract-operated patients in rural China: the caring is hip Study of Cataract Outcomes and Uptake of Services (SCOUTS), report No. 3.

PURPOSE: To determine the prevalence and impact on vision and visual function of ocular comorbidities in a rural Chinese cataract surgical program, and to devise strategies to reduce their associated burden. DESIGN: Cross-sectional cohort study. PARTICIPANTS: Persons undergoing cataract surgery by one of two recently trained local surgeons at a government-run village-level hospital in rural Guangdong between August 8 and December 31, 2005. INTERVENTIONS: Eligible subjects were invited to return for a comprehensive ocular examination and visual function interview 10 to 14 months after surgery. Prevalent ocular comorbid conditions were identified. MAIN OUTCOME MEASURES: Presenting and best-corrected vision, visual function, and treatability of the comorbidity. RESULTS: Of 313 persons operated within the study window, 242 (77%) could be contacted by telephone; study examinations and interviews were performed on 176 (74%). Examined subjects had a mean age of 69.4+/-10.5 years, 116 (66%) were female, and 149 (85%) had been blind (presenting vision < or = 6/60) in the operative eye before surgery. Among unoperated eyes, 89 of 109 (81.7%) had > or =1 ocular comorbidities, whereas for operated eyes the corresponding proportion was 72 of 211 (34.1%). The leading comorbidity among operated eyes was refractive error (43/72 [59.7%]), followed by glaucoma/glaucoma suspect (14/72 [19.4%]), whereas for unoperated eyes, it was cataract (80/92 [87.0%]), followed by refractive error (12/92 [13.0%]). Among operated eyes with comorbidities, 90.3% (65/72) had > or =1 comorbidities that were treatable. In separate models adjusting for age and gender, persons with > or =1 comorbidities in the operated eye had significantly worse presenting vision (P<0.001) than those without such findings, but visual function (P = 0.197) and satisfaction with surgery (P = 0.796) were unassociated with comorbidities. CONCLUSIONS: Ocular comorbidities are highly prevalent among persons undergoing cataract surgery in this rural Asian setting, and their presence is significantly associated with poorer visual outcomes. The fact that the great majority of comorbidities encountered in this program are treatable suggests that strategies to reduce their impact can be successful.

Distribution and visual impact of postoperative refractive error after cataract surgery in rural China: study of cataract outcomes and up-take of services report 4.

PURPOSE: To model the possible impact of using average-power intraocular lenses (IOLs) and evaluate the postoperative refractive error in patients having cataract surgery in rural China.SETTING: Rural Guangdong, China.METHODS: Patients having cataract surgery by local surgeons were examined and visual function was assessed 10 to 14 months after surgery. Subjective refraction at near and distance was performed bilaterally by an ophthalmologist. Patients had a target refraction of -0.50 diopter (D) based on ocular biometry.RESULTS: Of the 313 eligible patients, 242 (77%) could be contacted and 176 (74% of contacted patients, 56% overall) were examined. Examined patients had a mean age of 69.4 +/- 10.5 years. Of the 211 operated eyes, 73.2% were within +/-1.0 D of the target refraction after surgery. The best presenting distance vision was in patients within +/-1.0 D of plano and the best presenting near vision, in those with mild myopia (<-1.0 D to > or =2.0 D) (P= .005). However, patients with hyperopia (>+1.0 D) reported significantly better adjusted visual function than those with emmetropia or myopia (<-1.0 D). When the predicted use of an average-power IOL (median +21.5 D) was modeled, predicted visual acuity was significantly reduced (P= .001); however, predicted visual function was not significantly altered (P>.3).CONCLUSIONS: Accurate selection of postoperative refractive error was achieved by local surgeons in this rural area. Based on visual function results, aiming for mild postoperative myopia may not be suitable in this setting. Implanting average-power IOLs significantly reduced postoperative presenting vision, but not visual function.

Prevalence and determinants of spectacle nonwear among rural Chinese secondary schoolchildren: the Xichang Pediatric Refractive Error Study Report 3.

OBJECTIVE: To study spectacle wear among rural Chinese children. METHODS: Visual acuity, refraction, spectacle wear, and visual function were measured. RESULTS: Among 1892 subjects (84.7% of the sample), the mean (SD) age was 14.7 (0.8) years. Among 948 children (50.1%) potentially benefiting from spectacle wear, 368 (38.8%) did not own them. Among 580 children owning spectacles, 17.9% did not wear them at school. Among 476 children wearing spectacles, 25.0% had prescriptions that could not improve their visual acuity to better than 6/12. Therefore, 62.3% (591 of 948) of children needing spectacles did not benefit from appropriate correction. Children not owning and not wearing spectacles had better self-reported visual function but worse visual acuity at initial examination than children wearing spectacles and had a mean (SD) refractive error of -2.06 (1.15) diopter (D) and -2.78 (1.32) D, respectively. Girls (P < .001) and older children (P = .03) were more likely to be wearing their spectacles. A common reason for nonwear (17.0%) was the belief that spectacles weaken the eyes. Among children without spectacles, 79.3% said their families would pay for them (mean, US $15). CONCLUSIONS: Although half of the children could benefit from spectacle wear, 62.3% were not wearing appropriate correction. These children have significant uncorrected refractive errors. There is potential to support programs through spectacle sales.

A study of initial therapy for glaucoma in southern India: India Glaucoma Outcomes and Treatment (INGOT) Study.

PURPOSE: To compare initial glaucoma therapy with medications and trabeculectomy in southern India. METHODS: Patients aged ≥ 30 years newly diagnosed with glaucoma were randomized to trabeculectomy with 5-fluorouracil or medical therapy. Subjects with best-corrected vision <6/18 due to cataract underwent phacoemulsification (phaco/intraocular lens, IOL). Intraocular pressure (IOP), vision and visual function were assessed at 12 months. RESULTS: Patients assigned to medications and surgery received the expected therapy in 86% (172/199) and 64% (126/199) of cases, respectively. Forty patients (20%) assigned to surgery refused any treatment and 33 (17%) received medications. Among 199 patients randomized to medications, 52 (26.1%) underwent phaco/IOL, as did 89/199 (43.7%) of patients randomized to trabeculectomy. Baseline parameters of the two groups did not differ, nor did 1-year follow-up rates (medication 65%, trabeculectomy 58%, P = 0.15). Final IOP was lower with randomization to trabeculectomy (16.3 ± 5.1 mmHg) than medication (18.8 ± 6.7 mmHg, P < 0.0001). In regression models, randomization to trabeculectomy (P < 0.0001) was associated with lower IOP, and simultaneous trabeculectomy and cataract surgery was associated with higher IOP (P = 0.008) than trabeculectomy alone. Subjects receiving Phaco/IOL had significantly better final acuity (P < 0.0001) and visual function (P = 0.035), despite concurrent glaucoma treatment. Final visual acuity was worse in those receiving trabeculectomy in addition to cataract surgery, but this was of borderline significance (P = 0.06). CONCLUSIONS: Trabeculectomy lowered IOP significantly more than medical treatment, but with slightly greater loss of visual acuity. Combined phaco/IOL and trabeculectomy improved visual acuity with substantial IOP lowering.

Asthma control and exacerbations: two different sides of the same coin.

Purpose of review: Optimal asthma management includes both the control of asthma symptoms and reducing the risk of future asthma exacerbations. Traditionally, treatment has been adjusted largely on the basis of symptoms and lung function and for many patients, this approach delivers both excellent symptom control and reduced risk. However, the relationship between these two key components of the disease may vary between different asthmatic phenotypes and disease severities and there is increasing recognition of the need for more individualized treatment approaches.

Recent findings: A number of factors which predict exacerbation risk have been identified including demographic and behavioural features and specific inflammatory biomarkers. Type-2 cytokine-driven eosinophilic airways inflammation predisposes to frequent exacerbations and predicts response to corticosteroids, and the usefulness of sputum eosinophilia as both a marker of exacerbation risk and biomarker for adjustment of corticosteroid treatment has been established for some time. However, attempts to develop surrogate markers, which would be more straightforward to deliver in the clinic, have been challenging.

Summary: Some patients with asthma have persistent symptoms in the absence of type-2 cytokine driven-eosinophilic airways inflammation due to noncorticosteroid responsive mechanisms (T2-low disease). Composite biomarker strategies using easily measured surrogate indicators of type-2 inflammation (such as fractional exhaled nitric oxide, blood eosinophil count and serum periostin levels) may predict exacerbation risk better but it is unclear if they can be used to adjust corticosteroid treatment. Biomarkers will be used to target novel biologic treatments but additionally may be used to optimize corticosteroid treatment dose and act as prognostics for exacerbation risk and potentially other important longer term asthma outcomes.

Inhibition of protease-ENaC signaling improves mucociliary function in cystic fibrosis airways

Rationale: In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height
compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of ENaC have therapeutic potential in CF airways to reduce the hyperstimulated sodium and fluid absorption to levels which can restore airways hydration.

Objectives: To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function.

Methods: Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy) and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured by LDH assay.

Measurements and Results: QUB-TL1 inhibits extracellularly-located CAPs, including prostasin, matriptase and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells (AECs). QUB-TL1-mediated CAPs inhibition results in diminished ENaC-mediated Na+ absorption in CF AECs due to internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1-mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase-mediated ENaC activation and Pseudomonas aeruginosa exotoxin A induced cell death.

Conclusions: QUB-TL1 corrects aberrant CAP activities providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CFTR mutation.