Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic E. coli (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology – especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority of in vitro UTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder’s biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-based in vitro models have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments

Purification and Immunophenotypic Characterization of Human CD19+CD24hiCD38hi and CD19+CD24hiCD27+ B Cells.

Regulatory B cells (Bregs) have immunosuppressive capacity, primarily via the production of IL-10. IL-10 expression and immunosuppression have been described in a number of human B cell subsets, two of which include the CD19+CD24hiCD38hi and CD19+CD24hiCD27+ populations. In this chapter, we describe how to identify and isolate these subsets from peripheral blood B cells via flow cytometry. We also explain how to expand Bregs in culture and how to identify them based on intracellular expression of IL-10

Increasing Short-Stay Unplanned Hospital Admissions among Children in England; Time Trends Analysis '97-'06

BACKGROUND: Timely care by general practitioners in the community keeps children out of hospital and provides better continuity of care. Yet in the UK, access to primary care has diminished since 2004 when changes in general practitioners' contracts enabled them to 'opt out' of providing out-of-hours care and since then unplanned pediatric hospital admission rates have escalated, particularly through emergency departments. We hypothesised that any increase in isolated short stay admissions for childhood illness might reflect failure to manage these cases in the community over a 10 year period spanning these changes. METHODS AND FINDINGS: We conducted a population based time trends study of major causes of hospital admission in children 2 days. By 2006, 67.3% of all unplanned admissions were isolated short stays <2 days. The increases in admission rates were greater for common non-infectious than infectious causes of admissions. CONCLUSIONS: Short stay unplanned hospital admission rates in young children in England have increased substantially in recent years and are not accounted for by reductions in length of in-hospital stay. The majority are isolated short stay admissions for minor illness episodes that could be better managed by primary care in the community and may be evidence of a failure of primary care services

What are the living conditions and health status of those who don't report their migration status? a population-based study in Chile

BACKGROUND: Undocumented immigrants are likely to be missing from population databases, making it impossible to identify an accurate sampling frame in migration research. No population-based data has been collected in Chile regarding the living conditions and health status of undocumented immigrants. However, the CASEN survey (Caracterizacion Socio- Economica Nacional) asked about migration status in Chile for the first time in 2006 and provides an opportunity to set the base for future analysis of available migration data. We explored the living conditions and health of self-reported immigrants and respondents who preferred not to report their migration status in this survey. METHODS: Cross-sectional secondary analysis of CASEN survey in Chile in 2006. Outcomes: any disability, illness/accident, hospitalization/surgery, cancer/chronic condition (all binary variables); and the number of medical/emergency attentions received (count variables). Covariates: Demographics (age, sex, marital status, urban/rural, ethnicity), socioeconomic status (education level, employment status and household income), and material standard of living (overcrowding, sanitation, housing quality). Weighted regression models were estimated for each health outcome, crude and adjusted by sets of covariates, in STATA 10.0. RESULTS: About 1% of the total sample reported being immigrants and 0.7% preferred not to report their migration status (Migration Status - Missing Values; MS-MV). The MS-MV lived in more deprived conditions and reported a higher rate of health problems than immigrants. Some gender differences were observed by health status among immigrants and the MS-MV but they were not statistically significant. Regressions indicated that age, sex, SES and material factors consistently affected MS-MVs’ chance of presenting poor health and these patterns were different to those found among immigrants. Great heterogeneity in both the MS-MV and the immigrants, as indicated by wide confidence intervals, prevented the identification of other significantly associated covariates. CONCLUSION: This is the first study to look at the living conditions and health of those that preferred not to respond their migration status in Chile. Respondents that do not report their migration status are vulnerable to poor health and may represent undocumented immigrants. Surveys that fail to identify these people are likely to misrepresent the experiences of immigrants and further quantitative and qualitative research is urgently required

Implementation of immunohistochemistry on frozen ear notch tissue samples in diagnosis of bovine viral diarrhea virus in persistently infected cattle

<p>Abstract</p> <p>Background</p> <p>Bovine viral diarrhea is a contagious disease of domestic and wild ruminants and one of the most economically important diseases in cattle. Bovine viral diarrhea virus belongs to the genus <it>Pestivirus</it>, within the family <it>Flaviviridae</it>. The identification and elimination of the persistently infected animals from herds is the initial step in the control and eradication programs. It is therefore necessary to have reliable methods for diagnosis of bovine viral diarrhea virus. One of those methods is immunohistochemistry. Immunohistochemistry on formalin fixed, paraffin embedded tissue is a routine technique in diagnosis of persistently infected cattle from ear notch tissue samples. However, such technique is inappropriate due to complicated tissue fixation process and it requires more days for preparation. On the contrary, immunohistochemistry on frozen tissue was usually applied on organs from dead animals. In this paper, for the first time, the imunohistochemistry on frozen ear notch tissue samples was described.</p> <p>Findings</p> <p>Seventeen ear notch tissue samples were obtained during the period 2008-2009 from persistently infected cattle. Samples were fixed in liquid nitrogen and stored on -20°C until testing. Ear notch tissue samples from all persistently infected cattle showed positive results with good section quality and possibility to determinate type of infected cells.</p> <p>Conclusions</p> <p>Although the number of samples was limited, this study indicated that immunohistochemistry on formalin fixed paraffin embedded tissue can be successfully replaced with immunohistochemistry on frozen ear notch tissue samples in diagnosis of persistently infected cattle.</p

A p53-Dependent Response Limits Epidermal Stem Cell Functionality and Organismal Size in Mice with Short Telomeres

Telomere maintenance is essential to ensure proper size and function of organs with a high turnover. In particular, a dwarf phenotype as well as phenotypes associated to premature loss of tissue regeneration, including the skin (hair loss, hair graying, decreased wound healing), are found in mice deficient for telomerase, the enzyme responsible for maintaining telomere length. Coincidental with the appearance of these phenotypes, p53 is found activated in several tissues from these mice, where is thought to trigger cellular senescence and/or apoptotic responses. Here, we show that p53 abrogation rescues both the small size phenotype and restitutes the functionality of epidermal stem cells (ESC) of telomerase-deficient mice with dysfunctional telomeres. In particular, p53 ablation restores hair growth, skin renewal and wound healing responses upon mitogenic induction, as well as rescues ESCmobilization defects in vivo and defective ESC clonogenic activity in vitro. This recovery of ESC functions is accompanied by a downregulation of senescence markers and an increased proliferation in the skin and kidney of telomerase-deficient mice with critically short telomeres without changes in apoptosis rates. Together, these findings indicate the existence of a p53-dependent senescence response acting on stem/progenitor cells with dysfunctional telomeres that is actively limiting their contribution to tissue regeneration, thereby impinging on tissue fitness

Understanding Liver Health Using the National Center for Health Statistics

The National Center for Health Statistics (NCHS) is the principal health statistics agency for the United States. It seeks to provide accurate, relevant, and timely data on health status and utilization of health care. As such, the NCHS represents a tremendous repository of behavioral, biological, and clinical data that can be employed to identify issues and effect change in public policy related to liver health and disease. By providing an understanding of the rich, publicly available data systems within the NCHS, investigators may capitalize on an efficient means to shape current knowledge of liver disease

Computer-Based Screening of Functional Conformers of Proteins

A long-standing goal in biology is to establish the link between function, structure, and dynamics of proteins. Considering that protein function at the molecular level is understood by the ability of proteins to bind to other molecules, the limited structural data of proteins in association with other bio-molecules represents a major hurdle to understanding protein function at the structural level. Recent reports show that protein function can be linked to protein structure and dynamics through network centrality analysis, suggesting that the structures of proteins bound to natural ligands may be inferred computationally. In the present work, a new method is described to discriminate protein conformations relevant to the specific recognition of a ligand. The method relies on a scoring system that matches critical residues with central residues in different structures of a given protein. Central residues are the most traversed residues with the same frequency in networks derived from protein structures. We tested our method in a set of 24 different proteins and more than 260,000 structures of these in the absence of a ligand or bound to it. To illustrate the usefulness of our method in the study of the structure/dynamics/function relationship of proteins, we analyzed mutants of the yeast TATA-binding protein with impaired DNA binding. Our results indicate that critical residues for an interaction are preferentially found as central residues of protein structures in complex with a ligand. Thus, our scoring system effectively distinguishes protein conformations relevant to the function of interest

Antimicrobial activity of apple cider vinegar against Escherichia coli, Staphylococcus aureus and Candida albicans; downregulating cytokine and microbial protein expression

The global escalation in antibiotic resistance cases means alternative antimicrobials are essential. The aim of this study was to investigate the antimicrobial capacity of apple cider vinegar (ACV) against E. coli, S. aureus and C. albicans. The minimum dilution of ACV required for growth inhibition varied for each microbial species. For C. albicans, a 1/2 ACV had the strongest effect, S. aureus, a 1/25 dilution ACV was required, whereas for E-coli cultures, a 1/50 ACV dilution was required (p < 0.05). Monocyte co-culture with microbes alongside ACV resulted in dose dependent downregulation of inflammatory cytokines (TNFα, IL-6). Results are expressed as percentage decreases in cytokine secretion comparing ACV treated with non-ACV treated monocytes cultured with E-coli (TNFα, 99.2%; IL-6, 98%), S. aureus (TNFα, 90%; IL-6, 83%) and C. albicans (TNFα, 83.3%; IL-6, 90.1%) respectively. Proteomic analyses of microbes demonstrated that ACV impaired cell integrity, organelles and protein expression. ACV treatment resulted in an absence in expression of DNA starvation protein, citrate synthase, isocitrate and malate dehydrogenases in E-coli; chaperone protein DNak and ftsz in S. aureus and pyruvate kinase, 6-phosphogluconate dehydrogenase, fructose bisphosphate were among the enzymes absent in C.albican cultures. The results demonstrate ACV has multiple antimicrobial potential with clinical therapeutic implications

Effects of intrauterine food restriction and long-term dietary supplementation with L-arginine on age-related changes in renal function and structure of rats

We have previously demonstrated that restricting intrauterine food by 50% in 3-mo-old rats produced lower nephron numbers and early-onset hypertension, the latter being normalized by L-arginine administration. in 18-mo-old rats, such restriction increased glomerulosclerosis. in this study, we expanded our investigation, evaluating functional, morphologic, and immunohistochemical parameters in intrauterine-food-restricted 18-mo-old rats, either receiving L-arginine (RA18) or not (R18). Age-matched, non-food-restricted controls were assigned to similar groups with L-arginine (CA18) and without (C18). After weaning, L-arginine was given daily for 17 mo. No functional or morphologic changes were observed in C IS rats. the R18 rats developed early-onset hypertension, which persisted throughout the observation period, as well its significant proteinuria from 12 mo on. in RA18 rats, L-arginine decreased both blood pressure levels and proteinuria, and glomerular diameter was si,significantly smaller than in R18 rats (115.63 +/- 2.2 versus 134.8 +/- 1.0 mu m, p < 0.05). However, in RA18 rats, glomerular filtration rate remained depressed. Although L-arginine prevented glomerulosclerosis (R18 = 14%, RA18 = 4%; p < 0.05), glomerular expression of fibronectin and desmin was still greater in RA18 rats than in controls. Our data show that, although L-arginine prevented hypertension and proteinuria, glomerular injury still occurred, suggesting that intrauterine food restriction may be one of the leading causes of impaired renal function in adult life.Universidade Federal de São Paulo, Dept Physiol, EPM, Dept Physiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Morphol,Embrol Div, BR-04023900 São Paulo, BrazilUniv São Paulo, Ribeirao Preto Sch Med, Dept Physiol & Biophys, Brookline, MA 02146 USAUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Physiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Morphol,Embrol Div, BR-04023900 São Paulo, BrazilWeb of Scienc