Diabetes with hypertension as risk factors for adult dengue hemorrhagic fever in a predominantly dengue serotype 2 epidemic: a case control study

Background

Dengue hemorrhagic fever (DHF) is a severe form of dengue, characterized by bleeding and plasma leakage. A number of DHF risk factors had been suggested. However, these risk factors may not be generalized to all populations and epidemics for screening and clinical management of patients at risk of developing DHF. This study explored demographic and comorbidity risk factors for DHF in adult dengue epidemics in Singapore in year 2006 (predominantly serotype 1) and in year 2007–2008 (predominantly serotype 2).

Methods

A retrospective case-control study was conducted with 149 DHF and 326 dengue fever (DF) patients from year 2006, and 669 DHF and 1,141 DF patients from year 2007–2008. Demographic and reported comorbidity data were collected from patients previously. We performed multivariate logistic regression to assess the association between DHF and demographic and co-morbidities for year 2006 and year 2007–2008, respectively.

Results

Only Chinese (adjusted odds ratio [AOR] = 1.90; 95% confidence interval [CI]: 1.01–3.56) was independently associated with DHF in year 2006. In contrast, age groups of 30–39 years (AOR = 1.41; 95% CI:1.09–1.81), 40–49 years (AOR = 1.34; 95% CI:1.09–1.81), female (AOR = 1.57; 95% CI:1.28–1.94), Chinese (AOR = 1.67; 95% CI:1.24–2.24), diabetes (AOR = 1.78; 95% CI:1.06–2.97), and diabetes with hypertension (AOR = 2.16; 95%CI:1.18–3.96) were independently associated with DHF in year 2007–2008. Hypertension was proposed to have effect modification on the risk of DHF outcome in dengue patients with diabetes. Chinese who had diabetes with hypertension had 2.1 (95% CI:1.07–4.12) times higher risk of DHF compared with Chinese who had no diabetes and no hypertension.

Conclusions

Adult dengue patients in Singapore who were 30–49 years, Chinese, female, had diabetes or diabetes with hypertension were at greater risk of developing DHF during epidemic of predominantly serotype 2. These risk factors can be used to guide triaging of patients who require closer clinical monitoring and early hospitalization in Singapore, when confirmed in more studies.     

Derivatives of 1-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenyluracil and 5-Benzyluracil. Synthesis and Biological Properties

Abstract

A number of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil and -cytosine nucleosides substituted at the 5 position with a nitrophenyl or nitrobenzyl group were synthesized from 5-phenyl- and 5-benzyluracil via condensation of the fluorinated sugar, followed by nitration. The corresponding amino analogues were also prepared by reduction of the nitro nucleosides. The uracil nucleosides were converted into the corresponding cytosine nucleosides by way of the triazole intermediates. None of these nucleosides exhibited significant activity against herpes simplex virus type 1 in Vero cells. However, cytosine nucleosides containing the o-nitrophenyl, p-nitrophenyl, p-nitrobenzyl or p-aminobenzyl substituent were found to be toxic (even at 1 μM) to uninfected Vero cells, although they were essentially nontoxic in HL-60 cells. The 5′-monophosphates of the uracil nucleosides were inhibitors of the reaction catalyzed by purified Ehrlich ascites carcinoma thymidylate synthase, the 5-phenyluracil nucleotides causing a strong inhibition, competitive vs dUMP, described by the K_i value of 0.01 μM.     

The Microflora of Frozen Passionfruit Nectar Base

A considerable and varied microflora is introduced into passionfruit nectar base under present methods of production. In spite of the great acidity of the nectar base (pH range: 2.8 to 3.2), the high sucrose concentration (approximately 50%), and storage at -20 C, remnants of the microflora persist for a year or longer. During storage, however, there is a steady and gradual decrease, until after about 18 months the microflora is near to extinction. Sample regression lines show straight-line slopes for this diminution in numbers.

A battery of nine media was used to grow a representative aerobic flora. Purified cultures of isolates were identified to genera. Yeasts were the most numerous organisms in all samples, followed by molds, bacteria, and streptomycetes. The bacteria were the first group to disappear during storage. No fecal streptococci or gram-negative bacilli were found in any samples.

     

Nuclear targeting of IGF-1 receptor in orbital fibroblasts from Graves' disease: apparent role of ADAM17

Insulin-like growth factor-1 receptor (IGF-1R) comprises two subunits, including a ligand binding domain on extra- cellular IGF-1Rα and a tyrosine phosphorylation site located on IGF-1Rβ. IGF-1R is over-expressed by orbital fibroblasts in the autoimmune syndrome, Graves' disease (GD). When activated by IGF-1 or GD-derived IgG (GD-IgG), these fibroblasts produce RANTES and IL-16, while those from healthy donors do not. We now report that IGF-1 and GD-IgG provoke IGF-1R accumulation in the cell nucleus of GD fibroblasts where it co-localizes with chromatin. Nuclear IGF-1R is detected with anti-IGF-1Rα-specific mAb and migrates to approximately 110 kDa, consistent with its identity as an IGF-1R fragment. Nuclear IGF-1R migrating as a 200 kDa protein and consistent with an intact receptor was undetectable when probed with either anti-IGF-1Rα or anti-IGF-1Rβ mAbs. Nuclear redistribution of IGF-1R is absent in control orbital fibroblasts. In GD fibroblasts, it can be abolished by an IGF-1R-blocking mAb, 1H7 and by physiological concentrations of glucocorticoids. When cell-surface IGF-1R is cross-linked with (125)I IGF-1, (125)I-IGF-1/IGF-1R complexes accumulate in the nuclei of GD fibroblasts. This requires active ADAM17, a membrane associated metalloproteinase, and the phosphorylation of IGF-1R. In contrast, virally encoded IGF-1Rα/GFP fusion protein localizes equivalently in nuclei in both control and GD fibroblasts. This result suggests that generation of IGF-1R fragments may limit the accumulation of nuclear IGF-1R. We thus identify a heretofore-unrecognized behavior of IGF-1R that appears limited to GD-derived fibroblasts. Nuclear IGF-1R may play a role in disease pathogenesis.     

Effects of supercritical CO2 exposure and depressurization on immobilized lipase activity

Lipozyme IM20 from Novo Nordisk (Denmark) was examined after various treatments. Conditions were chosen to reflect those that would be considered in the design of an industrial process. A two-level factorial design was employed to assess the effects of pressurization/depressurization cycles, rate of depressurization and exposure length. A significant three-factor interaction was observed. Lowest residual activity was observed for runs in which the depressurization rate was 86–89 bar min^–1. Incubation for 12 h also yielded low residual activity but only when exposing the immobilized enzyme to one cycle. The highest residual activity was obtained for immobilized enzymes repeatedly exposed for periods of 12 h (5 times) with a depressurization rate of 4.3 to 4.45 bar min^–1. This effect may be due to the extraction of an inhibiting compound. Tuning process parameters can lead to a seven-fold change in residual activity.     

Aedes aegypti (L.) mosquitoes in Trinidad,West Indies: longevity case studies

Few laboratory and field studies have reported long survival periods for Ae. aegypti females and even fewer have designed experiments to characterize this important life history trait. This study was conducted under laboratory conditions to determine the number of blood meals taken by individual females, the number of eggs laid per individual female, the length of the gonotrophic cycle, and the duration of female survival. The results showed individual females oviposited between 670 and 1,500 eggs throughout their lifetimes, females undergoing large numbers of gonotrophic cycles and surviving up to 224 days. These results are discussed in the context of vector competence, unique alternating high and low oviposition patterns observed after week 14, and resource partitioning/allocation by older Ae. aegypti females after blood feeding.