A real-world observational study of dupilumab treatment in adult patients with prurigo nodularis

Abstract Background: Prurigo nodularis (PN) is a chronic inflammatory skin condition that has a significant unmet needs for effective treatment options. Objective: To assess the efficacy and safety of dupilumab in adult patients with PN refractory to traditional therapies. Methods: This ongoing, real-life study examined dupilumab treatment in 8 adult patients diagnosed with PN for at least 6 months. The included patients were prescribed 300 mg dupilumab biweekly for at least 16 weeks. Efficacy was the primary outcome by means of multiple standardized scale measurements while safety was also reported. Results: PN patients treated with dupilumab showed notable clinical improvement. After 16 weeks of dupilumab treatment, the mean Investigator Global Assessment (IGA) score reduced from 3.75 to 1.50. Patients mean Numerical Rating Scale Itch Intensity (NRSI), Dermatology Life Quality Index (DLQI), and Hospital Anxiety and Depression Scale (HADS) ratings reduced from 8.625, 15.13, and 14.50 to 1.563, 4.625, and 1.000 respectively. The majority of the patients (87.5%) reported dupilumab as effective while no adverse events have been reported. Study limitations: This study was limited to a small cohort of adult PN patients and a short-time observation period. Conclusions: Dupilumab is effective and tolerable in adult PN patients with significant improvement in skin lesions, itching, and quality of life.

Xuezhikang alleviates lipid accumulation via AMPK activation in hepatocellular steatosis model

Abstract Xuezhikang (XZK) is an extract of Chinese red yeast rice. It has multiple protective effects in cardiovascular systems. However, the underlying mechanism by which XZK affects free fatty acid (FFA)-induced lipogenesis in hepatocellular steatosis model is still unknown. Herein, we investigated this mechanism in HepG2 cells. The HepG2 cells were treated with palmitate acid (PA) to induce lipogenesis. Then the PA-induced HepG2 cells were subsequently treated with XZK. After 24 h of treatment, we determined the intracellular triglyceride (TG) contents and average areas of lipid droplets. To study the involvement of AMPK signaling pathway, we pre-treated the PA-induced HepG2 cells with Compound C, an AMPK inhibitor, before XZK treatment. Expressions of p-AMPK and AMPK were determined by Western blot. The results showed that XZK decreased TG content and lipid accumulation in hepatocellular steatosis model. Compound C abolished the effects of XZK. These results demonstrated for the first time that XZK protects hepatocytes against lipid accumulation induced by free fatty acids. Its effects may be mediated by the activation of AMPK pathway.

Socioeconomic status and risk of cardiovascular disease in 20 low-income, middle-income, and high-income countries: the Prospective Urban Rural Epidemiologic (PURE) study

Background Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status­wealth and education­differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorized as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. (AU)

Association of dietary nutrients with blood lipids and blood pressure in 18 countries: a cross-sectional analysis from the PURE study

BACKGROUND: The relation between dietary nutrients and cardiovascular disease risk markers in many regions worldwide is unknown. In this study, we investigated the effect of dietary nutrients on blood lipids and blood pressure, two of the most important risk factors for cardiovascular disease, in low-income, middle-income, and high-income countries.METHODS: We studied 125 287 participants from 18 countries in North America, South America, Europe, Africa, and Asia in the Prospective Urban Rural Epidemiology (PURE) study. Habitual food intake was measured with validated food frequency questionnaires. We assessed the associations between nutrients (total fats, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, carbohydrates, protein, and dietary cholesterol) and cardiovascular disease risk markers using multilevel modelling. The effect of isocaloric replacement of saturated fatty acids with other fats and carbohydrates was determined overall and by levels of intakes by use of nutrient density models. We did simulation modelling in which we assumed that the effects of saturated fatty acids on cardiovascular disease events was solely related to their association through an individual risk marker, and then compared these simulated risk marker-based estimates with directly observed associations of saturated fatty acids with cardiovascular disease events.

Does greater individual social capital improve the management of hypertension? Cross-national analysis of 61 229 individuals in 21 countries

INTRODUCTION:Social capital, characterised by trust, reciprocity and cooperation, is positively associated with a number of health outcomes. We test the hypothesis that among hypertensive individuals, those with greater social capital are more likely to have their hypertension detected, treated and controlled.METHODS:Cross-sectional data from 21 countries in the Prospective Urban and Rural Epidemiology study were collected covering 61 229 hypertensive individuals aged 35-70 years, their households and the 656 communities in which they live. Outcomes include whether hypertensive participants have their condition detected, treated and/or controlled. Multivariate statistical models adjusting for community fixed effects were used to assess the associations of three social capital measures: (1) membership of any social organisation, (2) trust in other people and (3) trust in organisations, stratified into high-income and low-income country samples.

A double-blinded randomized trial on growth and feeding tolerance with Saccharomyces boulardii CNCM I-745 in formula-fed preterm infants / Ensaio duplo-cego randomizado sobre crescimento e tolerância de alimentação com a Saccharomyces boulardii CNCM I-745 em neonatos prematuros alimentados com fórmula

Abstract Objective: The use of probiotics is increasingly popular in preterm neonates, as they may prevent necrotizing enterocolitis sepsis and improve growth and feeding tolerance. There is only limited literature on Saccharomyces boulardii CNCM I-745 (S. boulardii) in preterm infants. Method: A prospective, randomized, case-controlled trial with the probiotic S. boulardii (50 mg/kg twice daily) was conducted in newborns with a gestational age of 30-37 weeks and a birth weight between 1500 and 2500 g. Results: 125 neonates were enrolled; 63 in the treatment and 62 in the control group. Weight gain (16.14 ± 1.96 vs. 10.73 ± 1.77 g/kg/day, p < 0.05) and formula intake at maximal enteral feeding (128.4 ± 6.7 vs. 112.3 ± 7.2 mL/kg/day, p < 0.05) were significantly higher in the intervention group. Once enteral feeding was started, the time needed to reach full enteral feeding was significantly shorter in the probiotic group (0.4 ± 0.1 vs. 1.7 ± 0.5 days, p < 0.05). There was no significant difference in sepsis. Necrotizing enterocolitis did not occur. No adverse effects related to S. boulardii were observed. Conclusion: Prophylactic supplementation of S. boulardii at a dose of 50 mg/kg twice a day improved weight gain, improved feeding tolerance, and had no adverse effects in preterm infants >30 weeks old.

Resumo Objetivo: O uso de probióticos está cada vez mais popular em neonatos prematuros, já que podem prevenir a enterocolite necrosante (ECN) e a sepse e aumentar o crescimento e a tolerância de alimentação. Há apenas uma literatura limitada sobre a Saccharomyces boulardii CNCM I-745 (S. boulardii) em neonatos prematuros. Método: Um ensaio de caso-controle prospectivo randomizado com o probiótico S. boulardii (50 mg/kg duas vezes por dia) foi feito com recém-nascidos com idade gestacional de 30 a 37 semanas e peso ao nascer entre 1.500 e 2.500 g. Resultados: Foram incluídos 125 neonatos, 63 no grupo de tratamento e 62 no de controle. O ganho de peso (16,14 ± 1,96 em comparação com 10,73 ± 1,77 g/kg/dia, p < 0,05) e a ingestão de fórmula com nutrição enteral máxima (128,4 ± 6,7 em comparação com 112,3 ± 7,2 mL/kg/dia, p < 0,05) foram significativamente maiores no grupo de intervenção. Assim que a nutrição enteral foi iniciada, o tempo necessário para atingir a nutrição enteral completa foi significativamente menor no grupo probiótico (0,4 ± 0,1 em comparação com 1,7 ± 0,5 dia, p < 0,05). Não houve diferença significativa em sepse. Não ocorreu ECN. Não foi observado efeito colateral relacionado à S. boulardii. Conclusão: A suplementação profilática de S. boulardii em uma dose de 50 mg/kg duas vezes por dia melhorou o ganho de peso, aumentou a tolerância de alimentação e não teve efeito colateral em neonatos prematuros > 30 semanas de idade.

Assessing global risk factors for non-fatal injuries from road traffic accidents and falls in adultsaged 35-70 years in 17 countries: a cross-sectional analysis of the Prospective Urban Rural Epidemiological (PURE) study

Objectives To assess risk factors associated with non-fatal injuries (NFIs) from road traffic accidents (RTAs) or falls.Methods Our study included 151 609 participants from the Prospective Urban Rural Epidemiological study. Participants reported whether they experienced injuries within the past 12 months that limited normal activities. Additional questions elicited data on risk factors. We employed multivariable logistic regression to analyse data.Results Overall, 5979 participants (3.9% of 151 609) reported at least one NFI. Total number of NFIs was 6300: 1428 were caused by RTAs (22.7%), 1948 by falls (30.9%) and 2924 by other causes (46.4%). Married/common law status was associated with fewer falls, but not with RTA. Age 65–70 years was associated with fewer RTAs, but more falls; age 55–64 years was associated with more falls. Male versus female was associated with more RTAs and fewer falls. In lower-middle-income countries, rural residence was associated with more RTAs and falls; in low-income countries, rural residence was associated with fewer RTAs. Previous alcohol use was associated with more RTAs and falls; current alcohol use was associated with more falls. Education was not associated with either NFI type...

Anatomical characteristics of deer and sheep lumbar spines: comparison to the human lumbar spine / Características anatómicas de la columna vertebral de ciervos y ovejas: comparación con la columna vertebral humana

Deer and sheep spines are often used as models of the human spine. A prerequisite for the use of animal models is information regarding the interspecies differences in the parameters of general interest. This would clarify the limitations of each animal model and substantiate the applicability of the obtained results to humans. Since sufficient data appear to be currently unavailable, we sought to investigate the feasibility of using deer and sheep as animal models for studies on the human spine. The objective of this study was a thorough comparison of the anatomical parameters of deer and sheep spines with those of the human spine. We employed three-dimensional reconstructions of computed tomography images, generated using figure analysis software, which facilitated quantitative analysis of the linear and curvature parameters and the geometric index of the vertebral bodies. Our findings represent a comprehensive database of the anatomical characteristics of the deer and sheep lumbar spines and their comparisons with those of the human lumbar spine. This study provides insight into the similarities and differences in the vertebral geometries between the human spine and the deer and sheep spines. We found that the differences are minimal and that they do not greatly compromise the utility of deer and sheep lumbar spines as models of the human lumbar spine.

La columna vertebral de ciervos y ovejas se utiliza frecuentemente como modelo de la columna vertebral humana. Un requisito previo para el uso de modelos animales es la información con respecto a las diferencias entre especies en los parámetros de interés general, lo que aclara las limitaciones de cada modelo animal y fundamenta la aplicabilidad de los resultados obtenidos para los seres humanos. Debido a que existen datos suficientes actualmente, hemos intentado investigar la viabilidad de utilizar ciervos y ovejas como modelos animales para los estudios sobre la columna vertebral humana. El objetivo fue realizar una comparación exhaustiva de los parámetros anatómicos de las columnas de ciervos y ovejas, con los de la columna vertebral humana. Empleamos reconstrucciones tridimensionales de imágenes de tomografía computadorizada, mediante un programa de análisis de la figura, lo que facilitó el análisis cuantitativo de los parámetros lineales y de la curvatura y el índice geométrico de las vértebras. Nuestros hallazgos representan una amplia base de datos de las características anatómicas de la columna lumbar de los ciervos y ovejas y sus comparaciones con las de la columna lumbar humana. Este estudio proporciona información sobre las similitudes y diferencias en las geometrías vertebrales entre la columna vertebral humana y las columnas de venado y oveja. Se encontró que las diferencias son mínimas y que no comprometen el uso de la columna de ciervos y ovejas como modelos de la columna lumbar humana.

Integrin-ß1, not integrin-ß5, mediates osteoblastic differentiation and ECM formation promoted by mechanical tensile strain

BACKGROUND: Mechanical strain plays a great role in growth and differentiation of osteoblast. A previous study indicated that integrin-ß (ß1, ß5) mediated osteoblast proliferation promoted by mechanical tensile strain. However, the involvement of integrin-ß; in osteoblastic differentiation and extracellular matrix (ECM) formation induced by mechanical tensile strain, remains unclear. RESULTS: After transfection with integrin-ß1 siRNA or integrin-ß5 siRNA, mouse MC3T3-E1 preosteoblasts were cultured in cell culture dishes and stimulated with mechanical tensile strain of 2500 microstrain (µÎµ) at 0.5 Hz applied once a day for 1 h over 3 or 5 consecutive days. The cyclic tensile strain promoted osteoblastic differentiation of MC3T3-E1 cells. Transfection with integrin-ß1 siRNA attenuated the osteoblastic diffenentiation induced by the tensile strain. By contrast, transfection with integrin-ß5 siRNA had little effect on the osteoblastic differentiation induced by thestrain. At thesametime, theresultofECM formation promoted by the strain, was similar to the osteoblastic differentiation. CONCLUSION: Integrin-ß1 mediates osteoblast differentiation and osteoblastic ECM formation promoted by cyclic tensile strain, and integrin-ß5 is not involved in the osteoblasts response to the tensile strain.

A Novel Method to Evaluate the Community BuiltEnvironment Using Photographs – Environmental Profileof a Community Health (EPOCH) Photo NeighbourhoodEvaluation Tool

Previous research has shown that environments with features that encourage walking are associated withincreased physical activity. Existing methods to assess the built environment using geographical information systems (GIS)data, direct audit or large surveys of the residents face constraints, such as data availability and comparability, when used tostudy communities in countries in diverse parts of the world. The aim of this study was to develop a method to evaluatefeatures of the built environment of communities using a standard set of photos. In this report we describe the method ofphoto collection, photo analysis instrument development and inter-rater reliability of the instrument.Methods/Principal Findings: A minimum of 5 photos were taken per community in 86 communities in 5 countriesaccording to a standard set of instructions from a designated central point of each community by researchers at each site. Astandard pro forma derived from reviewing existing instruments to assess the built environment was developed and used toscore the characteristics of each community. Photo sets from each community were assessed independently by threeobservers in the central research office according to the pro forma and the inter-rater reliability was compared by intra-classcorrelation (ICC). Overall 87% (53 of 60) items had an ICC of $0.70, 7% (4 of 60) had an ICC between 0.60 and 0.70 and 5% (3of 60) items had an ICC #0.50.Conclusions/Significance: Analysis of photos using a standardized protocol as described in this study offers a means toobtain reliable and reproducible information on the built environment in communities in very diverse locations around theworld. The collection of the photographic data required minimal training and the analysis demonstrated high reliability forthe majority of items of interest.