Regional variation in hemoglobin distribution among individuals with chronic kidney disease: the ISN International Network of Chronic Kidney Disease (iNET-CKD) Cohorts

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin.Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model.Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17–49 ml/min) and 3 pediatric cohorts (median eGFR range of 26–45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7–6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R2 7%–44% across cohorts).Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations.</p

Topical Application of Activity-based Probes for Visualization of Brain Tumor Tissue

Several investigators have shown the utility of systemically delivered optical imaging probes to image tumors in small animal models of cancer. Here we demonstrate an innovative method for imaging tumors and tumor margins during surgery. Specifically, we show that optical imaging probes topically applied to tumors and surrounding normal tissue rapidly differentiate between tissues. In contrast to systemic delivery of optical imaging probes which label tumors uniformly over time, topical probe application results in rapid and robust probe activation that is detectable as early as 5 minutes following application. Importantly, labeling is primarily associated with peri-tumor spaces. This methodology provides a means for rapid visualization of tumor and potentially infiltrating tumor cells and has potential applications for directed surgical excision of tumor tissues. Furthermore, this technology could find use in surgical resections for any tumors having differential regulation of cysteine cathepsin activity

Testing the Efficacy of a Multi-Component DNA-Prime/DNA-Boost Vaccine against Trypanosoma cruzi Infection in Dogs

Immunization of dogs with DNA-prime/DNA-boost vaccine (TcVac1) enhanced the Trypanosoma cruzi-specific type 1 antibody and CD8+ T cell responses that resulted in an early control of acute parasitemia and a moderate decline in pathological symptoms during chronic phase. Further improvement of vaccine-induced immunity would be required to achieve clinical and epidemiological benefits and prevent transmission of parasites from vaccinated/infected dogs to triatomines

The role of sex in the pathophysiology of pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease characterised by increased pulmonary vascular resistance and pulmonary artery remodelling as result of increased vascular tone and vascular cell proliferation, respectively. Eventually, this leads to right heart failure. Heritable PAH is caused by a mutation in the bone morphogenetic protein receptor-II (BMPR-II). Female susceptibility to PAH has been known for some time, and most recent figures show a female-to-male ratio of 4:1. Variations in the female sex hormone estrogen and estrogen metabolism modify FPAH risk, and penetrance of the disease in BMPR-II mutation carriers is increased in females. Several lines of evidence point towards estrogen being pathogenic in the pulmonary circulation, and thus increasing the risk of females developing PAH. Recent studies have also suggested that estrogen metabolism may be crucial in the development and progression of PAH with studies indicating that downstream metabolites such as 16α-hydroxyestrone are upregulated in several forms of experimental pulmonary hypertension (PH) and can cause pulmonary artery smooth muscle cell proliferation and subsequent vascular remodelling. Conversely, other estrogen metabolites such as 2-methoxyestradiol have been shown to be protective in the context of PAH. Estrogen may also upregulate the signalling pathways of other key mediators of PAH such as serotonin

Regional Variation in Hemoglobin Distribution Among Individuals With CKD: the ISN International Network of CKD Cohorts

Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin

UVB suscetibilidade como fator de risco para o desenvolvimento da hanseníase virchowiana UVB susceptibility as a risk factor to the development of lepromatous leprosy

FUNDAMENTOS: A radiação ultravioleta B (RUVB) é o mais importante fator ambiental capaz de modificar a função imunológica da pele humana. OBJETIVO: estudar a associação entre o fenótipo de suscetibilidade ou resistência à radiação RUVB e as formas polares da hanseníase. MATERIAL E MÉTODOS: foram avaliados 38 pacientes com hanseníase virchowiana (MHV) e 87 pacientes com hanseníase tuberculoide (MHT) de acordo com a classificação de Ridley e Jopling (1966). Todos os pacientes foram submetidos ao teste para determinação do fenótipo de suscetibilidade ou resistência à RUVB por meio da aplicação de um disco de dinitroclorobenzeno (DNCB) a 2% em uma área de pele previamente irradiada com duas vezes a dose eritematosa mínima (DEM). Após 21 dias, outra aplicação de um disco similar de DNCB a 0,05% na região escapular (área não exposta à RUVB) foi realizada para avaliar se houve sensibilização, com leitura após 48 horas. Os pacientes que apresentaram reação positiva ao DNCB foram considerados UVB-resistentes e o oposto foi considerado para aqueles que não apresentaram resposta (UVB-suscetíveis). RESULTADOS: A frequência de UVB-suscetíveis foi de 63,2% (24 pacientes) no grupo MHV e 34,4% (30 pacientes) no grupo MHT (OR = 3,26; IC = 1,36-7,87; x² = 7,73; p = 0,005). CONCLUSÃO: Os resultados sugerem que a UVB-suscetibilidade é um fator de risco para o desenvolvimento da MHV.<br>BACKGROUNDS: Ultraviolet radiation B (UVRB) is the most important environmental factor capable of altering the immune function of human skin. OBJECTIVE: To evaluate the association of the phenotypes of susceptibility or resistance to ultraviolet radiation B (UVRB) and the polar forms of leprosy. MATERIAL AND METHODS: We evaluated 38 patients with lepromatous leprosy (LL) and 87 patients with tuberculoid (TT) leprosy, according to the classification by Ridley and Jopling (1966). All the patients were submitted to a test to determine the phenotypes of susceptibility or resistance to UVRB through the application of a 2% dinitrochlorobenzene (DNCB) disc to a previously irradiated area with twice the minimal erythema dose (MED). After 21 days, a similar disc soaked in 0.05% DNCB was applied to the scapular area (unexposed to UVRB) to check for sensitiveness, with reading of the results after 48 hours. The patients that showed a positive reaction to DNCB were considered resistant (UVB-R) and those who did not show any reaction were considered susceptible (UVB-S). RESULTS: The frequency of UVB-S individuals was 63.2% (24 patients) in the LL group and 34.4% (30 patients) in the TT group (OR=3.26; IC=1.36 - 7.87; x²=7.73; p=0.005). CONCLUSION: Our results suggest that UVB-susceptibility is a risk factor to the development of lepromatous leprosy (LL)