Asymptomatic bacterial colonization of the urinary bladder (asymptomatic bacteriuria, ABU) can prevent bladder colonization by uropathogens and thus symptomatic urinary tract infection (UTI). Deliberate bladder colonization with Escherichia coli ABU isolate 83972 has been shown to outcompete uropathogens and prevent symptomatic UTI by bacterial interference. Many ABU isolates evolved from uropathogenic ancestors and, although attenuated, may still be able to express virulence-associated factors. Our aim was to screen for efficient and safe candidate strains that could be used as alternatives to E. coli 83972 for preventive and therapeutic bladder colonization. To identify ABU E. coli strains with minimal virulence potential but maximal interference efficiency, we compared nine ABU isolates from diabetic patients regarding their virulence- and fitness-associated phenotypes in vitro, their virulence in a murine model of sepsis and their genome content. We identified strains in competitive growth experiments, which successfully interfere with colonization of ABU isolate 83972 or uropathogenic E. coli strain 536. Six isolates were able to outcompete E. coli 83972 and two of them also outcompeted UPEC 536 during growth in urine. Superior competitiveness was not simply a result of better growth abilities in urine, but seems also to involve expression of antagonistic factors. Competitiveness in urine did not correlate with the prevalence of determinants coding for adhesins, iron uptake, toxins, and antagonistic factors. Three ABU strains (isolates 61, 106, and 123) with superior competitiveness relative to ABU model strain 83972 display low in vivo virulence in a murine sepsis model, and susceptibility to antibiotics. They belong to different phylogroups and differ in the presence of ExPEC virulence- and fitness-associated genes. Importantly, they all lack marked cytotoxic activity and exhibit a high LD50 value in the sepsis model. These strains represent promising candidates for a more detailed assessment of relevant fitness traits in urine and their suitability for therapeutic bladder colonization.

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A lthough the number of children and youth with type 2 diabetes is increasing, a clear case definition that describes children with type 2 diabetes at presentation remains elusive. Most initial diagnoses are decided on the clinical picture at presentation (1). Characteristics and risk factors have been outlined in several review and clinical articles (2-4). The purpose of this study was to describe the characteristics of youth presenting for an initial visit to the outpatient clinic of a large tertiary children's care center and diagnosed with type 2 diabetes.For this retrospective study, data were abstracted from a consecutive sample of 98 patients' medical records at Texas Children's Hospital starting 1 January 1998 and ending 31 October 2001. The sample's mean age at diagnosis was 13.6 years (SD 2.33; range 8.7-18.4 years). Fifty-one percent of the children were female and 49% were male (female: male ratio 1:1). For 43% race/ethnicity was not specified; the remaining participants were 28.6% African American, 22.4% Hispanic, 3.1% non-Hispanic white, and 3.1% Asian. Of those for whom data were available, a maternal history of type 2 diabetes was reported by 32.7% (18/55) and an unspecified type of diabetes by 12.7% (7/55). Twenty-seven percent (13/47) reported a father with type 2 diabetes and 21% (10/47) an unspecified type of diabetes.Mean BMI was 34.67 kg/m 2 (SD 6.91). Ninety-three percent had a BMI Ն95th percentile. All but three of the individuals had BMIs Ն85th percentile. Of those for whom data were recorded, acanthosis nigricans was identified in 94% (48/51). A Tanner stage of 3, 4, or 5 was identified in 73.2% (49/67).Blood pressure readings indicated that 49.4% (41/83) had a systolic (SBP) and 10.8% (9/83) a diastolic (DBP) Ն95th percentile for age, sex, and height (n ϭ 83). Fifty-five percent (46/83) had SBP and 19.3% (16/83) DBP readings Ն90th percentile for blood pressure. Of 72 pulse rates recorded, 2.6% were Ն95th percentile for age. Average HbA 1c was 10.38 (SD 3.52) (n ϭ 95).Of those who had symptoms documented in the medical record, 83.6% (56/ 67) reported polyuria, 83.9% (52/62) polydipsia , and 61% (36/59) polyphagia. Seventy-five percent reported both polyuria and polydipsia (46/61). Of the cases available, 46.2% (24/52) reported all three of the polys at initial presentation, 46.8% (29/62) had weight loss, and 62.5% (30/48) had ketones. Of those for whom islet cell antibody data were recorded (50/98), 49 had JDF units Ͻ5. Fifty-three percent were started on insulin, 46.3% on oral agents, and 13.7% on both insulin and oral agent (n ϭ 96). Initial mean insulin dose was 0.6 units/kg.Our sample is similar to those described in previous reports except for a more even ratio of female to male subjects, a greater percent with elevated SBP and/or DBP, and more individuals reporting weight loss. We are the first to report blood pressure by the 95th and 90th percentiles and the first to report pulse rate. These data contribute to the growing body of clinical evidence defining the characteristics of ...

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It has been reported that urinary interleukin-6 (IL-6) and IL-8 levels are decreased in adult diabetic women with asymptomatic bacteriuria (ASB) when compared with non-diabetic women with ASB. Such impaired cytokine excretion might play a role in the higher prevalence of ASB among diabetic subjects. The aim of this study was to examine the urinary IL profile in children and young adults with type 1 diabetes mellitus (T1DM) with and without ASB. Midstream clean voiding urine samples were collected and cultured from 133 patients with T1DM (age: 15.6 +/- 5.7 yr) and 178 controls (14.1 +/- 4.7 yr) for two consecutive days. ASB was diagnosed in the case of >or=10(5) bacteria/mL. The urinary IL-6 and IL-8 concentrations were determined, and the presence of leukocyturia was also recorded. The prevalence of ASB was 16.5% in diabetic subjects and 2.8% in controls (p = 0.001). There was no difference between the diabetic and the control groups in the prevalence of 'IL-6-uria' (21.9 vs. 18.0%; p = 0.41), but IL-8 was more frequently detectable in the diabetic group (47.4 vs. 27.5%; p = 0.001). In individuals with ASB, the IL-8 level was similar in the diabetic (median: 70.0 pg/mg creatinine) and control group (42.3 pg/mg creatinine; p = 0.8). Indeed, the IL-8 levels were higher in diabetic subjects with ASB as compared with those without it (70.0 vs. <3.1 pg/mg creatinine; p = 0.001), and there was a significant association between the urinary IL-8 concentration and the bacterial count (p = 0.001). Diabetic patients with leukocyturia had higher IL-8 concentration than those without it (20.9 vs. <3.1 pg/mg creatinine; p = 0.003). Weak significant correlation was found between urinary IL-8 and hemoglobin A1c (HbA1c) (r = 0.4; p = 0.002). The sensitivity and specificity of leukocyturia were 50 and 89.9% in the whole population and those of IL-8 were 74.1 and 67.5%, respectively. In diabetic patients, 36.4% of the bacteriuria were gram-negative and 63.6% gram-positive. Our results suggest that diabetic children with ASB mount an IL-8 response to pathogens, which is comparable to non-diabetic children with bacteriuria. Thus, early in the natural history of diabetes, there are no significant changes in the IL response of children with ASB, as previously reported in adults.

Apart from retinopathy and hypertension, the prevalence of microvascular complications was relatively low. Considering the limitations of questionnaire studies, laboratory screening is warranted to assess the true prevalence of comorbidities and complications.

Escherichia coli can colonize the urinary bladder without causing a disease response in the host. This asymptomatic bacteriuria (ABU) can protect against recurrent symptomatic urinary tract infection by virulent bacteria. Here, we report the whole-genome sequences of nine E. coli ABU isolates from diabetic patients.

We present the case history of a 3-year-old girl who was examined because of severe dystrophy. In the background, cow's milk allergy was found, but her body weight was unchanged after eliminating milk from her diet. Other types of malabsorption were excluded. Based on nasal regurgitation and facial dysmorphisms, the possibility of DiGeorge syndrome was suspected and was confirmed by fluorescence in situ hybridization. The authors suggest a new feature associated with DiGeorge syndrome.