Giardia infections in Cuban children: the genotypes circulating in a rural population

Stool samples containing Giardia duodenalis cysts were collected from 95 primary-school children in central Cuba, and preserved by storing at -20 degrees C in 70% ethanol. Clinical data were collected for each child. Although 57% of the children were asymptomatic, the remaining 43% each reported between one and three symptoms. Following cyst quantification and isolation, molecular analyses were attempted on all cyst isolates, with the focus on the parasite's beta-giardin and glutamate-dehydrogenase (gdh) genes. Unfortunately, the cyst-preservation procedure appeared to have a deleterious effect on the cysts, since genotyping data could only be obtained for 20 of the 95 isolates. These data indicated, however, an approximately equal distribution between assemblage A (nine isolates) and assemblage B (11 isolates). Children found to be excreting relatively large numbers of cysts were more likely to be symptomatic than children who were excreting fewer cysts, and children with Giardia isolates from assemblage B were more likely to have symptomatic infections than children with isolates from assemblage A. Although considerable sequence variability was seen in the assemblage-B isolates, the assemblage-A isolates were relatively genetically homogeneous. This is the first publication from the Caribbean in which the Giardia genotypes circulating within the population have been identified, the first from the Americas providing information on associations between clinical presentation and the assemblage of the infecting Giardia, and the first to indicate that levels of cyst excretion may have clinical significance.     

Colonization by S. Aureus increases the EASI and the number of appointments by patients with atopic dermatitis: cohort with 93 patients

BACKGROUND

Atopic dermatitis leads to epidermal barrier dysfunction and bacteria colonization. The relationship of the last factor with the severity of the disease and the frequency of exacerbation is not fully known.

OBJECTIVES

Verify the severity of the atopic dermatitis and the number of appointments generated by dermatosis, comparing patients colonized with patients not colonized by S. aureus. Verify the frequency of colonization by methicillin resistant Staphylococcus aureus acquired in the community.

METHODS

Cohort study with a 12 months follow-up, in a sample of patients from Porto Alegre, RS public network. Cultures in active injuries and nasal cavities were carried out as well as methicillin sensitivity tests to S. aureus. The severity of atopic dermatitis was defined by Eczema Area and Severity Index (EASI).

RESULTS

We included 93 patients, 43% female and 56% male, 26 colonized by S. aureus in the nasal orifices, 56 in the skin damage. The mean of initial Eczema Area and Severity Index was 5.5 and final 3.9. The initial Eczema Area and Severity Index of patients colonized by S. aureus in the skin and nasal cavity was larger than the number of patients without colonization(p< 0.05). During the period of one year, in average, there were six appointments/patient. There was linear correlation between the number of appointments during one year and the inicial Eczema Area and Severity Index (r = 0,78). There were no patients with methicillin resistant Staphylococcus aureus acquired in the community.

CONCLUSION

There is a relevant influence of staphylococcal colonization on the severity of atopic dermatitis and the number of appointments required by its exacerbation. Methicillin resistance among those affected by S. aureus does not seem to be an emergent problem, in this Brazilian sample.     

Dasatinib overrides imatinib resistance mediated by the F359I residue mutation in two patients with chronic myeloid leukemia

Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard-dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic regimen to dasatinib at a dose of 100 mg once daily in both patients. This change resulted in the achievement of complete cytogenetic remission in patient 1 after 4 months and a major molecular response within 2 and 3 months in both patients. Detection of the F359I mutation in our two cases likely explains the suboptimal response to imatinib in case 1 and the failure in case 2. This implies that in such cases dasatinib should be considered to effectively suppress the mutated clones.     

White blood cell count is associated with carotid and femoral atherosclerosis

ObjectiveRelationship of high sensitivity C-reactive protein (hsCRP) with Metabolic Syndrome (MetS) is well documented in many populations, but comprehensive data is lacking in Indian population. Thus, we set out to investigate the association of hsCRP levels with MetS and its features and the effect of obesity and insulin resistance on this association in urban Indians.MethodsThis is a cross-sectional study that included 9517 subjects comprising 4066 subjects with MetS. MetS was defined according to the modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria for Asians.ResultsMedian levels of hsCRP were considerably higher in individuals with MetS with higher levels in women compared to men. Among the features of MetS, waist circumference was most strongly correlated with hsCRP levels (r = 0.28) and contributed maximally (β = 0.025 mg/l ln hsCRP, P = 7.4 × 10^?147). Subjects with high risk hsCRP levels (>3 mg/l) were at high risk of MetS (OR (95% CI) = 1.65(1.41–1.92), P = 1.7 × 10^?10). Risk of MetS increased in a dose dependent manner from low risk to high risk hsCRP category with increase in BMI and HOMA-IR.ConclusionsOur findings suggest that hsCRP predicts the risk of MetS, independent of obesity and insulin resistance, and therefore, can be a valuable tool to aid the identification of individuals at risk of MetS. The study provides a lead for future investigation for effects of hsCRP, obesity, and insulin resistance on MetS in this population.     

Rapid Screening Tests for Determining In Vitro Susceptibility of Herpes Simplex Virus Clinical Isolates

The susceptibility of human herpes simplex virus (HSV) to acyclovir (ACV) was determined with the use of a single dose of the drug (1 and 2 μg of ACV per ml for HSV-1 and HSV-2, respectively) in two rapid assays: a rapid cytopathic effect inhibitory assay (Rapid CIA) and a rapid dye uptake assay (Rapid DUA). These tests allow the simultaneous determination of virus titer and susceptibility to ACV at a determined viral concentration (100 50% tissue culture infective doses and 100 50% dye uptake units). These tests were compared with a conventional susceptibility assay (dye uptake assay) and showed similar results. Indeterminate results with the Rapid CIA appeared in 3 of 30 samples. With the use of both Rapid CIA and Rapid DUA, we were able to determine the susceptibility of 100% of the isolates. The rapid tests, unlike conventional assays, are able to provide susceptibility results within 3 days after the virus has been isolated from a clinical specimen and could thus play a direct role in therapeutic decisions.     

不同方法校正的肌肉质量与老年2型糖尿病躯体功能的相关性比较

目的 探索不同方法校正的肌肉质量与老年2型糖尿病(type 2 diabetes mellitus, T2DM)躯体功能的相关性。方法 纳入首都医科大学宣武医院内分泌科≥60岁的T2DM患者248例,测定血红蛋白(hemoglobin, Hb),糖化血红蛋白(glycosylated hemoglobin A1c, HbA1c)、空腹血糖(fasting plasma glucose, FPG),维生素D、握力、步速、起立行走计时(timed go and up, TUG)测试时间,计算体质量指数(body mass index, BMI)。并用双能X线吸收检测仪测定四肢骨骼肌肌肉质量(appendicular skeletal muscle mass, ASM),分别用身高(height, ht)的平方(ASM/ht²)和BMI(ASM/BMI)两种方法对肌肉质量校正,分析躯体功能的影响因素。结果 偏相关分析结果显示, ASM/BMI均与握力、步速、TUG时间显著相关(分别为r=0.636, P<0.001;r=0.191, P=0.003;r=- 0.143, P=0.026),而ASM/ht²仅与握力相关(r=0.513, P<0.001)。多元Logistic回归分析结果显示,低ASM/BMI显著影响患者的步速和TUG时间(分别为OR=4.73,95%CI: 1.54~14.60,P=0.007; OR=2.92,95%CI: 1.12~7.63,P=0.029),而ASM/ht²对患者躯体功能无显著影响。结论 低ASM/BMI而不是低ASM/ht²与老年T2DM患者差的躯体功能相关,ASM/BMI可能是更适合于T2DM患者的肌肉质量校正方法。     

基于合成致死的抗肿瘤药物研发进展

合成致死是指在两个非致死基因中任何一个基因发生突变均不影响细胞存活,但当两个基因同时发生突变时,能够特异性导致细胞死亡。恶性肿瘤由于DNA复制和修复的错误积累了大量的基因突变,因此可抑制与这些基因具有合成致死关系的另一个基因,从而选择性地杀死肿瘤细胞,而不影响正常细胞。近年来,合成致死原理已经成功应用于肿瘤的靶向治疗。本文综述了合成致死的基本原理、合成致死相互作用的筛选方法、合成致死在DNA损伤修复领域的研究现状、合成致死在抗肿瘤药物研发中的挑战及展望。