The Biocompatibility Analysis of Artificial Mucin-Like Glycopolymers.

The ocular surface is covered by a tear film consisting of an aqueous/mucin phase and a superficial lipid layer. Mucins, highly O-glycosylated proteins, are responsible for lubrication and ocular surface protection. Due to contact lens wear or eye disorders, lubrication of the ocular surface can be affected. Artificial glycopolymers which mimic natural mucins could be efficient in ophthalmic therapy. Various neutral, positively, and negatively charged mucin-mimicking glycopolymers were synthesized (n = 11), cultured in different concentrations (1%, 0.1%, and 0.01% w/v) with human corneal epithelial cells (HCE), and analyzed by various cytotoxicity/viability, morphology, and immunohistochemistry (IHC) assays. Six of the eleven glycopolymers were selected for further analysis after cytotoxicity/viability assays. We showed that the six selected glycopolymers had no cytotoxic effect on HCE cells in the 0.01% w/v concentration. They did not negatively affect cell viability and displayed both morphology and characteristic markers as untreated control cells. These polymers could be used in the future as mucin-mimicking semi-synthetic materials for lubrication and protection of the ocular surface.

Effect of age and sex on the associations between potential modifiable risk factors and both type 2 diabetes and impaired fasting glycaemia among West African adults.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is becoming one of the leading causes of morbidity and mortality worldwide, including among Africans. Knowledge of the association between traditional risk factors and both diabetes and pre-diabetes, and whether these differ by age and sex, is important for designing targeted interventions. However, little is known about these associations for African populations. METHODS: The study used data from WHO STEPS surveys, comprising 15,520 participants (6,774 men and 8,746 women) aged 25-64 years, from 5 different West African countries, namely Burkina Faso (4,711), Benin (3,816), Mali (1,772), Liberia (2,594), and Ghana (2,662). T-test and chi-square tests were used to compare differences in the prevalence of traditional risk factors for both sexes. Multinomial logistic regression was conducted to ascertain the relative risks (RR) and 95% confidence intervals (CI) for both T2DM and impaired fasting glucose (IFG) relating to each risk factor, including obesity [defined by BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)], high blood pressure (HBP), fruit and vegetable consumption, physical inactivity, alcohol consumption, and smoking. Models for each of these traditional risk factors and interactions with age and sex were fitted. RESULTS: Factors associated with T2DM and IFG were age, obesity [defined by BMI, WC, WHtR, and WHR], HBP, smoking, physical inactivity, and fruit and vegetable consumption (p < 0.05). Analysis of interaction effects showed few significant differences in associations between risk factors and T2DM according to age or sex. Significant interaction with age was observed for HBP*age and T2DM [RR; 1.20, 95% CI: (1.01, 1.42)) (p = 0.04)], WHtR*age and T2DM [RR; 1.23, 95% CI: (1.06, 1.44) (p = 0.007)] and WHR*age and IFG [RR: 0.79, 95% CI: (0.67, 0.94) (p = 0.006)]. Some interactions with age and sex were observed for the association of alcohol consumption and both IFG and T2DM, but no clear patterns were observed. CONCLUSION: The study found that with very few exceptions, associations between traditional risk factors examined and both IFG and T2DM did not vary by age or sex among the West African population. Policies and public health intervention strategies for the prevention of T2DM and IFG should target adults of any age or sex in West Africa.

Associations between obesity indices and both type 2 diabetes and impaired fasting glucose among West African adults: Results from WHO STEPS surveys.

BACKGROUND AND AIM: Various obesity indices such as BMI, waist circumference (WC), waist-hip ratio, (WHR) and waist-to-height ratio (WHtR) are associated with the risk of type 2 Diabetes Mellitus (T2DM). Given few studies examining the strength of the association in this population, we aimed to identify which obesity indices are most strongly associated with T2DM and impaired fasting glucose (IFG) among adults from five West African countries. METHODS AND RESULTS: Data from 15,520 participants from the World Health Organisation (WHO) STEPs surveys in Burkina Faso, Benin, Mali, Liberia, and Ghana were included in analyses. Multinomial logistic regression was used to calculate the relative risk (RR) per standard deviation (SD) of each anthropometric measure, modelled as both continuous variables and as categorical variables based on established cut-points. In the analyses with continuous variables, the unadjusted RRs for T2DM per SD were 1.30 (1.23, 1.37) for body mass index (BMI); 1.56 (1.46, 1.67) for WC; 2.57 (2.15, 3.09) for WHtR and 1.16 (1.03, 1.31) for WHR. WHtR showed the strongest association with T2DM in all adjusted analyses. For models using categorical variables based on established cut-points, obesity defined using waist circumference (OB-WC) and OB-BMI showed the strongest associations with T2DM, and OB-WHR, the weakest association in all adjusted analyses. CONCLUSION: WHtR and WC appear to be the indices most strongly associated with T2DM and IFG respectively. Given its simplicity, WC may be the metric that most usefully conveys risk for T2DM in West African adults.

The state of hypertension care in 44 low-income and middle-income countries: a cross-sectional study of nationally representative individual-level data from 1·1 million adults.

BACKGROUND: Evidence from nationally representative studies in low-income and middle-income countries (LMICs) on where in the hypertension care continuum patients are lost to care is sparse. This information, however, is essential for effective targeting of interventions by health services and monitoring progress in improving hypertension care. We aimed to determine the cascade of hypertension care in 44 LMICs-and its variation between countries and population groups-by dividing the progression in the care process, from need of care to successful treatment, into discrete stages and measuring the losses at each stage. METHODS: In this cross-sectional study, we pooled individual-level population-based data from 44 LMICs. We first searched for nationally representative datasets from the WHO Stepwise Approach to Surveillance (STEPS) from 2005 or later. If a STEPS dataset was not available for a LMIC (or we could not gain access to it), we conducted a systematic search for survey datasets; the inclusion criteria in these searches were that the survey was done in 2005 or later, was nationally representative for at least three 10-year age groups older than 15 years, included measured blood pressure data, and contained data on at least two hypertension care cascade steps. Hypertension was defined as a systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or reported use of medication for hypertension. Among those with hypertension, we calculated the proportion of individuals who had ever had their blood pressure measured; had been diagnosed with hypertension; had been treated for hypertension; and had achieved control of their hypertension. We weighted countries proportionally to their population size when determining this hypertension care cascade at the global and regional level. We disaggregated the hypertension care cascade by age, sex, education, household wealth quintile, body-mass index, smoking status, country, and region. We used linear regression to predict, separately for each cascade step, a country's performance based on gross domestic product (GDP) per capita, allowing us to identify countries whose performance fell outside of the 95% prediction interval. FINDINGS: Our pooled dataset included 1 100 507 participants, of whom 192 441 (17·5%) had hypertension. Among those with hypertension, 73·6% of participants (95% CI 72·9-74·3) had ever had their blood pressure measured, 39·2% of participants (38·2-40·3) had been diagnosed with hypertension, 29·9% of participants (28·6-31·3) received treatment, and 10·3% of participants (9·6-11·0) achieved control of their hypertension. Countries in Latin America and the Caribbean generally achieved the best performance relative to their predicted performance based on GDP per capita, whereas countries in sub-Saharan Africa performed worst. Bangladesh, Brazil, Costa Rica, Ecuador, Kyrgyzstan, and Peru performed significantly better on all care cascade steps than predicted based on GDP per capita. Being a woman, older, more educated, wealthier, and not being a current smoker were all positively associated with attaining each of the four steps of the care cascade. INTERPRETATION: Our study provides important evidence for the design and targeting of health policies and service interventions for hypertension in LMICs. We show at what steps and for whom there are gaps in the hypertension care process in each of the 44 countries in our study. We also identified countries in each world region that perform better than expected from their economic development, which can direct policy makers to important policy lessons. Given the high disease burden caused by hypertension in LMICs, nationally representative hypertension care cascades, as constructed in this study, are an important measure of progress towards achieving universal health coverage. FUNDING: Harvard McLennan Family Fund, Alexander von Humboldt Foundation.

Sociodemographic inequities associated with participation in leisure-time physical activity in sub-Saharan Africa: an individual participant data meta-analysis.

BACKGROUND: Leisure-time physical activity (LTPA) is an important contributor to total physical activity and the focus of many interventions promoting activity in high-income populations. Little is known about LTPA in sub-Saharan Africa (SSA), and with expected declines in physical activity due to rapid urbanisation and lifestyle changes we aimed to assess the sociodemographic differences in the prevalence of LTPA in the adult populations of this region to identify potential barriers for equitable participation. METHODS: A two-step individual participant data meta-analysis was conducted using data collected in SSA through 10 population health surveys that included the Global Physical Activity Questionnaire. For each sociodemographic characteristic, the pooled adjusted prevalence and risk ratios (RRs) for participation in LTPA were calculated using the random effects method. Between-study heterogeneity was explored through meta-regression analyses and tests for interaction. RESULTS: Across the 10 populations (N = 26,022), 18.9% (95%CI: 14.3, 24.1; I2 = 99.0%) of adults (≥ 18 years) participated in LTPA. Men were more likely to participate in LTPA compared with women (RR for women: 0.43; 95%CI: 0.32, 0.60; P < 0.001; I2 = 97.5%), while age was inversely associated with participation. Higher levels of education were associated with increased LTPA participation (RR: 1.30; 95%CI: 1.09, 1.55; P = 0.004; I2 = 98.1%), with those living in rural areas or self-employed less likely to participate in LTPA. These associations remained after adjusting for time spent physically active at work or through active travel. CONCLUSIONS: In these populations, participation in LTPA was low, and strongly associated with sex, age, education, self-employment and urban residence. Identifying the potential barriers that reduce participation in these groups is necessary to enable equitable access to the health and social benefits associated with LTPA.

Delayed presentation of melanoma-associated retinopathy and subsequent resolution with cytoreduction surgery.

BACKGROUND: To present a case of melanoma-associated retinopathy (MAR) which manifested 26 months prior to a formal diagnosis of melanoma. METHODS: Case report. RESULTS: A 72-year-old female presented with bilateral continuous photopsia consistent with MAR of 7-months duration. At this point, visual function appeared normal with the exception of mildly impaired colour vision (10/17 Ishihara plates). The flash electroretinographic (ERG) revealed extinguished rod responses, a normal a-wave and reduced b-wave (electronegative ERG) on the maximal combined response, absent oscillatory potentials and broadened a-wave trough on the cone response. Multifocal ERG (mfERG) responses were delayed and demonstrated atypical morphology. Nineteen months after the initial presentation, her visual symptoms had progressed significantly with constant debilitating photopsia in combination with 13 kg weight loss. Biopsy of a now evident left axillary mass demonstrated a metastatic high-grade malignant melanoma. No primary was detected, and an axillary lymph node clearance was undertaken. Subsequently, visual symptoms resolved with corresponding improvement in the ERG over the next 18 months. Rod responses recovered such that the amplitude was at the lower limit of normal and the mfERG response delay lessened. Unfortunately, the melanoma recurred and the patient passed away 6 months later. Visual symptoms did not recur. CONCLUSION: We present a case which demonstrates MAR may precede the formal diagnosis of melanoma by up to 26 months. The potential for improvement in the rod visual function persists over a period of years with normalisation of an electronegative waveform. In this case, cytoreductive surgery resulted in complete resolution of the MAR, which did not return even with a recurrence of the tumour.

New and highly efficient methodology for screening high-yield strains of cytotoxic deacetylmycoepoxydiene (DAM).

AIMS: To establish a highly efficient methodology for screening high yield strains of cytotoxic deacetylmycoepoxydiene (DAM), to meet the need of research on its mechanism of anti-tumor properties and in vivo toxicity studies. METHODS AND RESULTS: A simple, sensitive, and highly repetitive screening procedure 'Antimicrobial-TLC-HPLC' (ATH) was established for the rapid obtaining of high-yielding DAM mutants to replace the time and labor intensive anti-tumor activity assay (MTT). With this ATH method, four highly yielding DAM mutants were selected out of 5000 total mutants, one of which, M4-143, showed yields of more than 300 times (250·3 mg l(-1) ) that of the parent strain A123. CONCLUSIONS: The ATH method developed in this work has proven to be both economical and highly efficient with the screening of 1200 mutants in a one week time period, thusly shortening the expenditure of time and labor, without missing a single high-yield mutant. Due to these characteristics, it is superior to other HTS screening methods described in earlier literature. The mutant M4-143 has a good genetic stability and can be used for further research. SIGNIFICANCE AND IMPACT OF THE STUDY: This ATH screening method is not only perfect for screening high-yield DAM mutants, but also, it is suitable to screen the strain libraries for those strains that have the ability to produce natural metabolites with antitumor activity.

Analysis of Attained Height and Diabetes Among 554,122 Adults Across 25 Low- and Middle-Income Countries.

OBJECTIVE: The prevalence of type 2 diabetes is rising rapidly in low-income and middle-income countries (LMICs), but the factors driving this rapid increase are not well understood. Adult height, in particular shorter height, has been suggested to contribute to the pathophysiology and epidemiology of diabetes and may inform how adverse environmental conditions in early life affect diabetes risk. We therefore systematically analyzed the association of adult height and diabetes across LMICs, where such conditions are prominent. RESEARCH DESIGN AND METHODS: We pooled individual-level data from nationally representative surveys in LMICs that included anthropometric measurements and diabetes biomarkers. We calculated odds ratios (ORs) for the relationship between attained adult height and diabetes using multilevel mixed-effects logistic regression models. We estimated ORs for the pooled sample, major world regions, and individual countries, in addition to stratifying all analyses by sex. We examined heterogeneity by individual-level characteristics. RESULTS: Our sample included 554,122 individuals across 25 population-based surveys. Average height was 161.7 cm (95% CI 161.2-162.3), and the crude prevalence of diabetes was 7.5% (95% CI 6.9-8.2). We found no relationship between adult height and diabetes across LMICs globally or in most world regions. When stratifying our sample by country and sex, we found an inverse association between adult height and diabetes in 5% of analyses (2 out of 50). Results were robust to alternative model specifications. CONCLUSIONS: Adult height is not associated with diabetes across LMICs. Environmental factors in early life reflected in attained adult height likely differ from those predisposing individuals for diabetes.

Enhanced cellular immunity in macaques following a novel peptide immunotherapy.

Advances in treating and preventing AIDS depend on understanding how human immunodeficiency virus (HIV) is eliminated in vivo and on the manipulation of effective immune responses to HIV. During the development of assays quantifying the elimination of fluorescent autologous cells coated with overlapping 15-mer simian immunodeficiency virus (SIV) or HIV-1 peptides, we made a remarkable observation: the reinfusion of macaque peripheral blood mononuclear cells, or even whole blood, pulsed with SIV and/or HIV peptides generated sharply enhanced SIV- and HIV-1-specific T-cell immunity. Strong, broad CD4+- and CD8+-T-cell responses could be enhanced simultaneously against peptide pools spanning 87% of all SIV- and HIV-1-expressed proteins-highly desirable characteristics of HIV-specific immunity. De novo hepatitis C virus-specific CD4+- and CD8+-T-cell responses were generated in macaques by the same method. This simple technique holds promise for the immunotherapy of HIV and other chronic viral infections.

Metastatic lung and pleural malignancy presenting as bilateral acute anterior uveitis.

Anterior uveitis is associated with a variety of underlying systemic diseases but the association between bilateral acute anterior uveitis (BAAU) and lung and pleural malignancy is not widely recognized. The case is described here of a 61-year-old woman presenting to an eye clinic with BAAU. A routine chest radiograph performed principally to exclude pulmonary sarcoidosis revealed an intrapulmonary mass and she was subsequently found to have widespread lung and pleural malignancies. Evidence is discussed that suggests a link and potential aetiology between BAAU and lung and pleural malignancies. The present case shows the virtue of requesting a chest radiograph in patients presenting with BAAU, even in the absence of other symptoms or clinical findings.

Efficacy of DNA and fowlpox virus priming/boosting vaccines for simian/human immunodeficiency virus.

Further advances are required in understanding protection from AIDS by T-cell immunity. We analyzed a set of multigenic simian/human immunodeficiency virus (SHIV) DNA and fowlpox virus priming and boosting vaccines for immunogenicity and protective efficacy in outbred pigtail macaques. The number of vaccinations required, the effect of DNA vaccination alone, and the effect of cytokine (gamma interferon) coexpression by the fowlpox virus boost was also studied. A coordinated induction of high levels of broadly reactive CD4 and CD8 T-cell immune responses was induced by sequential DNA and fowlpox virus vaccination. The immunogenicity of regimens utilizing fowlpox virus coexpressing gamma interferon, a single DNA priming vaccination, or DNA vaccines alone was inferior. Significant control of a virulent SHIV challenge was observed despite a loss of SHIV-specific proliferating T cells. The outcome of challenge with virulent SHIV(mn229) correlated with vaccine immunogenicity except that DNA vaccination alone primed for protection almost as effectively as the DNA/fowlpox virus regimen despite negligible immunogenicity by standard assays. These studies suggest that priming of immunity with DNA and fowlpox virus vaccines could delay AIDS in humans.