Tissue Tropism and Target Cells of NSs-Deleted Rift Valley Fever Virus in Live Immunodeficient Mice

Rift Valley fever, caused by a member of the Bunyaviridae family, has spread during recent years to most sub-Saharan African countries, in Egypt and in the Arabian peninsula. The virus can be transmitted by insect vectors or by direct contacts with infectious tissues. The analysis of virus replication and dissemination in laboratory animals has been hampered by the need to euthanize sufficient numbers of animals and to assay appropriate organs at various time points after infection to evaluate the viral replication. By following the bioluminescence and fluorescence of Rift Valley fever viruses expressing light reporters, we were able to track the real-time dissemination of the viruses in live immunodeficient mice. We showed that the first infected organs were the thymus, spleen and liver, but the liver rapidly became the main location of viral replication. Phagocytes also appeared as important targets, and their systemic depletion by use of clodronate liposomes decreased the number of viruses in the blood, delayed the viral dissemination and prolonged the survival of the infected mice

Sialyl-Lewis(X) Glycoantigen Is Enriched on Cells with Persistent HIV Transcription during Therapy

A comprehensive understanding of the phenotype of persistent HIV-infected cells, transcriptionally active and/or transcriptionally inactive, is imperative for developing a cure. The relevance of cell-surface glycosylation to HIV persistence has never been explored. We characterize the relationship between cell-surface glycomic signatures and persistent HIV transcription in vivo. We find that the cell surface of CD4+ T cells actively transcribing HIV, despite suppressive therapy, harbors high levels of fucosylated carbohydrate ligands, including the cell extravasation mediator Sialyl-LewisX (SLeX), compared with HIV-infected transcriptionally inactive cells. These high levels of SLeX are induced by HIV transcription in vitro and are maintained after therapy in vivo. Cells with high-SLeX are enriched with markers associated with HIV susceptibility, signaling pathways that drive HIV transcription, and pathways involved in leukocyte extravasation. We describe a glycomic feature of HIV-infected transcriptionally active cells that not only differentiates them from their transcriptionally inactive counterparts but also may affect their trafficking abilities

Renal and vascular diseases are under-counted as underlying causes of death in diabetic populations: Prospective study of 150,000 Mexicans followed for 10 years

Conventional coding rules for death certificates substantially over-count diabetes mellitus as the underlying cause, and correspondingly under-count other conditions such as vascular or renal disease. For, among patients with diabetes reported on the death certificate, conventional rules ascribe vascular or renal deaths to the accompanying diabetes. Thus, although “underlying cause” is defined appropriately by the World Health Organization (WHO) as “the disease or injury which initiated the train of morbid events leading directly to death”, conventional WHO coding rules do not necessarily provide it. We explore the relevance of this to renal and vascular mortality in Mexico, where diabetes is common, and assess separately the substantial overall importance of diabetes

Renal and vascular diseases are under-counted as underlying causes of death in diabetic populations: Prospective study of 150,000 Mexicans followed for 10 years

Conventional coding rules for death certificates substantially over-count diabetes mellitus as the underlying cause, and correspondingly under-count other conditions such as vascular or renal disease. For, among patients with diabetes reported on the death certificate, conventional rules ascribe vascular or renal deaths to the accompanying diabetes. Thus, although “underlying cause” is defined appropriately by the World Health Organization (WHO) as “the disease or injury which initiated the train of morbid events leading directly to death”, conventional WHO coding rules do not necessarily provide it. We explore the relevance of this to renal and vascular mortality in Mexico, where diabetes is common, and assess separately the substantial overall importance of diabetes

Diabetes and premature mortality in Mexico City: Blood-based prospective study of 15,000 Mexican adults with 12 years’ mortality follow-up

Most large prospective studies of the effects of diabetes on mortality have focused on high-income countries with good glycemic control, and in those countries diabetes less than doubles all-cause mortality rates. Few large, prospective studies have been conducted in middle-income countries where obesity and diabetes have become common and glycemic control may be poor

Diabetes and premature mortality in Mexico City: Blood-based prospective study of 15,000 Mexican adults with 12 years’ mortality follow-up

Most large prospective studies of the effects of diabetes on mortality have focused on high-income countries with good glycemic control, and in those countries diabetes less than doubles all-cause mortality rates. Few large, prospective studies have been conducted in middle-income countries where obesity and diabetes have become common and glycemic control may be poor

Adiposity and blood pressure in 110,000 Mexican adults

Previous studies have reached differing conclusions about the importance of general versus central markers of adiposity to blood pressure, leading to suggestions that population-specific adiposity thresholds may be needed. We examined the relevance of adiposity to blood pressure among 111,911 men and women who, when recruited into the Mexico City Prospective Study, were aged 35-89, had no chronic disease, and were not taking antihypertensives. Linear regression was used to estimate the effects on systolic (SBP) and diastolic (DBP) blood pressure of two markers of general adiposity (body-mass index [BMI, height-adjusted-weight [HtaW]) and four markers of central adiposity (waist-circumference [WC], hip-circumferences [HC], their ratio [WHR] and waist-height ratio [WHtR]), adjusted for relevant confounders. Mean (SD) adiposity levels were: BMI (28.7±4.5 kg/m2); HtaW (70.2±11.2 kgs); WC (93.3±10.6 cms); HC (104.0±9.0 cms); WHR (0.90±0.06); and WHtR (0.60±0.07). Associations with blood pressure were linear with no threshold levels below which lower general or central adiposity was not associated with lower blood pressure. On average, each 1 standard deviation (SD) higher measured adiposity marker was associated with a 3 mmHg higher SBP and 2 mmHg higher DBP (SEs <0.1 mmHg), but for the WHR, associations were only half as strong. General adiposity associations were independent of central adiposity, but central adiposity associations were substantially reduced by adjustment for general adiposity. Findings were similar for men and women. In Mexican adults, often overweight or obese, markers of general adiposity were stronger predictors of blood pressure than measured markers of central adiposity, with no threshold effects

Adiposity and blood pressure in 110,000 Mexican adults

Previous studies have reached differing conclusions about the importance of general versus central markers of adiposity to blood pressure, leading to suggestions that population-specific adiposity thresholds may be needed. We examined the relevance of adiposity to blood pressure among 111,911 men and women who, when recruited into the Mexico City Prospective Study, were aged 35-89, had no chronic disease, and were not taking antihypertensives. Linear regression was used to estimate the effects on systolic (SBP) and diastolic (DBP) blood pressure of two markers of general adiposity (body-mass index [BMI, height-adjusted-weight [HtaW]) and four markers of central adiposity (waist-circumference [WC], hip-circumferences [HC], their ratio [WHR] and waist-height ratio [WHtR]), adjusted for relevant confounders. Mean (SD) adiposity levels were: BMI (28.7±4.5 kg/m2); HtaW (70.2±11.2 kgs); WC (93.3±10.6 cms); HC (104.0±9.0 cms); WHR (0.90±0.06); and WHtR (0.60±0.07). Associations with blood pressure were linear with no threshold levels below which lower general or central adiposity was not associated with lower blood pressure. On average, each 1 standard deviation (SD) higher measured adiposity marker was associated with a 3 mmHg higher SBP and 2 mmHg higher DBP (SEs <0.1 mmHg), but for the WHR, associations were only half as strong. General adiposity associations were independent of central adiposity, but central adiposity associations were substantially reduced by adjustment for general adiposity. Findings were similar for men and women. In Mexican adults, often overweight or obese, markers of general adiposity were stronger predictors of blood pressure than measured markers of central adiposity, with no threshold effects