A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug-resistant uropathogenic Escherichia coli ST131

Background. Escherichia coli O25b:H4-ST131 represents a predominant clone of multidrug-resistant uropathogens currently circulating worldwide in hospitals and the community. Urinary tract infections (UTIs) caused by E. coli ST131 are typically associated with limited treatment options and are often recurrent. Methods. Using established mouse models of acute and chronic UTI, we mapped the pathogenic trajectory of the reference E. coli ST131 UTI isolate, strain EC958. Results. We demonstrated that E. coli EC958 can invade bladder epithelial cells and form intracellular bacterial communities early during acute UTI. Moreover, E. coli EC958 persisted in the bladder and established chronic UTI. Prophylactic antibiotic administration failed to prevent E. coli EC958–mediated UTI. However, 1 oral dose of a small-molecular-weight compound that inhibits FimH, the type 1 fimbriae adhesin, significantly reduced bacterial colonization of the bladder and prevented acute UTI. Treatment of chronically infected mice with the same FimH inhibitor lowered their bladder bacterial burden by >1000-fold. Conclusions. In this study, we provide novel insight into the pathogenic mechanisms used by the globally disseminated E. coli ST131 clone during acute and chronic UTI and establish the potential of FimH inhibitors as an alternative treatment against multidrug-resistant E. coli.

Molecular characterization of Escherichia coli strains that cause symptomatic and asymptomatic urinary tract infections

The differences between Escherichia coli strains associated with symptomatic and asymptomatic urinary tract infections (UTIs) remain to be properly determined. Here we examined the prevalence of plasmid types and bacteriocins, as well as genetic relatedness, in a defined collection of E. coli strains that cause UTIs. Comparative analysis identified a subgroup of strains with a high number of virulence genes (VGs) and microcins M/H47. We also identified associations between microcin genes, VGs, and specific plasmid types.

Oral contraceptives prevent the development of endometriosis in the chicken chorioallantoic membrane model

Background: Fundamental and genetic differences between women in the endometrium may cause some to develop endometriosis, whereas others (to not. Oral contraceptives (OC) may have in effect on the endometrium, rendering the development of endometriosis less likely. Study Design: Endometrium front women using CC (OCE) and menstrual endometrium (ME) from normal cycling women were transplanted onto the chicken chorioallantoic membrane (CAM), and endometriosis-like lesion formation was evalualed. Microarray gene expression profiling was performed to identify, differentially expressed genes in the endometrium front these groups. Microarray data were validated by real-time PCR. Results: Less endometriosis-like lesions were formed after transplantation of OCE than after transplantation of ME (p<.05). Most of the differentially expressed genes belong to the TGF beta superfamily. Real-time PCR validation revealed that inhibin beta A (INHBA) expression was significantly decreased in OCE its compared to ME. Conclusion: OC use affects the characteristics Of endometrium, rendering it less potent to develop into endometriosis. (C) 2008 Elsevier Inc. All rights reserved.

Diagnostic potential of saliva : current state and future applications

BACKGROUND: Over the past 10 years, the use of saliva as a diagnostic fluid has gained attention and has become a translational research success story. Some of the current nanotechnologies have been demonstrated to have the analytical sensitivity required for the use of saliva as a diagnostic medium to detect and predict disease progression. However, these technologies have not yet been integrated into current clinical practice and work flow. CONTENT: As a diagnostic fluid, saliva offers advantages over serum because it can be collected noninvasively by individuals with modest training, and it offers a cost-effective approach for the screening of large populations. Gland-specific saliva can also be used for diagnosis of pathology specific to one of the major salivary glands. There is minimal risk of contracting infections during saliva collection, and saliva can be used in clinically challenging situations, such as obtaining samples from children or handicapped or anxious patients, in whom blood sampling could be a difficult act to perform. In this review we highlight the production of and secretion of saliva, the salivary proteome, transportation of biomolecules from blood capillaries to salivary glands, and the diagnostic potential of saliva for use in detection of cardiovascular disease and oral and breast cancers. We also highlight the barriers to application of saliva testing and its advancement in clinical settings. SUMMARY: Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance. (C) 2011 American Association for Clinical Chemistry

Diagnostic potential of saliva : state of the art and future applications [Potenziale diagnostico della saliva: stato dell’arte e applicazioni future]

Over the past 10 years, the use of saliva as a diagnostic fluid has gained attention and has become a translational research success story. Some of the current nanotechnologies have been demonstrated to have the analytical sensitivity required for the use of saliva as a diagnostic medium to detect and predict disease progression. However, these technologies have not yet been integrated into current clinical practice and work flow. As a diagnostic fluid, saliva offers advantages over serum because it can be collected noninvasively by individuals with modest training, and it offers a cost-effective approach for the screening of large populations. Gland-specific saliva can also be used for diagnosis of pathology specific to one of the major salivary glands. There is minimal risk of contracting infections during saliva collection, and saliva can be used in clinically challenging situations, such as obtaining samples from children or handicapped or anxious patients, in whom blood sampling could be a difficult act to perform. In this review we highlight the production of and secretion of saliva, the salivary proteome, transportation of biomolecules from blood capillaries to salivary glands, and the diagnostic potential of saliva for use in detection of cardiovascular disease and oral and breast cancers. We also highlight the barriers to application of saliva testing and its advancement in clinical settings. Saliva has the potential to become a first-line diagnostic sample of choice owing to the advancements in detection technologies coupled with combinations of biomolecules with clinical relevance.

miRNAs in head and neck cancer revisited

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world and the 5th most commonly occurring cancer. Tobacco smoking, alcohol consumption and human papilloma virus (HPV) infections have been associated with the occurrence of HNSCC. Despite advances that have been made in HNSCC treatment, smoking-associated HNSCC patients still exhibit a poor 5 year survival rate (30-50 %) and a concomitant poor quality of life. The major clinical challenge to date lies in the early detection of dysplastic lesions,which can progress to malignancy. In addition, there are currently no tools available to monitor HNSCC patients for early stages of local recurrences or distant metastases. In the recent past, micro-RNAs (miRNA) have been assessed for their role in cancer initiation and progression, including HNSCC. It is now well-established that deregulation of these single stranded, small non-coding, 19-25 nt RNAs can e.g. enhance the expression of oncogenes or subdue the expression of tumor suppressor genes. The aims of this review are three-fold: first to retrieve from the literature miRNAs that have specifically been associated with HNSCC, second to group these miRNAs into those regulating tumor initiation, progression and metastasis, and third to discern miRNAs related to smoking-associated HNSCC versus HPV-associated HNSCC development. This review gives an overview on the miRNAs regulating the development of head and neck cancers. The ultimate establishment of miRNA expression profiles that are HNSCC specific, and miRNAs that orchestrate altered gene and protein expression levels in HNSCC, could pave the way for a better understanding of the mechanism underlying its pathogenesis and the development of novel, targeted therapies.

Healthcare-associated infections in Australia : time for national surveillance

Abstract Objective. Healthcare-associated infection (HAI) surveillance programs are critical for infection prevention. Australia does not have a comprehensive national HAI surveillance program. The purpose of this paper is to provide an overview of established international and Australian statewide HAI surveillance programs and recommend a pathway for the development of a national HAI surveillance program in Australia. Methods. This study examined existing HAI surveillance programs through a literature review, a review of HAI surveillance program documentation, such as websites, surveillance manuals and data reports and direct contact with program representatives. Results. Evidence from international programs demonstrates national HAI surveillance reduces the incidence of HAIs. However, the current status of HAI surveillance activity in Australian states is disparate, variation between programs is not well understood, and the quality of data currently used to compose national HAI rates is uncertain. Conclusions. There is a need to develop a well-structured, evidence-based national HAI program in Australia to meet the increasing demand for validated reliable national HAI data. Such a program could be leveraged off the work of existing Australian and international programs.

The effectiveness of dietary counselling versus oral nutrition supplements in improving nutritional intake in malnourished patients with Chronic Obstructive Pulmonary Disease (COPD)

The evidence for nutritional support in COPD is almost entirely based on oral nutritional supplements (ONS) yet despite this dietary counseling and food fortification (DA) are often used as the first line treatment for malnutrition. This study aimed to investigate the effectiveness of ONS vs. DA in improving nutritional intake in malnourished outpatients with COPD. 70 outpatients (BMI 18.4 SD 1.6 kg/m2, age 73 SD 9 years, severe COPD) were randomised to receive a 12-week intervention of either ONS or DA (n 33 ONS vs. n 37 DA). Paired t-test analysis revealed total energy intakes significantly increased with ONS at week 6 (+302 SD 537 kcal/d; p = 0.002), with a slight reduction at week 12 (+243 SD 718 kcal/d; p = 0.061) returning to baseline levels on stopping supplementation. DA resulted in small increases in energy that only reached significance 3 months post-intervention (week 6: +48 SD 623 kcal/d, p = 0.640; week 12: +157 SD 637 kcal/d, p = 0.139; week 26: +247 SD 592 kcal/d, p = 0.032). Protein intake was significantly higher in the ONS group at both week 6 and 12 (ONS: +19.0 SD 25.0 g/d vs. DA: +1.0 SD 13.0 g/d; p = 0.033 ANOVA) but no differences were found at week 26. Vitamin C, Iron and Zinc intakes significantly increased only in the ONS group. ONS significantly increased energy, protein and several micronutrient intakes in malnourished COPD patients but only during the period of supplementation. Trials investigating the effects of combined nutritional interventions are required.

Preventing infections through cleaner hospitals project

While many Australian hospitals have good infection control practices, research about the role cleaning in the hospital environment plays in preventing infections is limited.

Changes in healthcare-associated infections after the introduction of a national hand hygiene initiative

Introduction: Interventions that prevent healthcare-associated infections should lead to fewer deaths and shorter hospital stays. Cleaning hands with soap and water or alcohol rub is an effectiveway to prevent the transmission of organisms, but compliance is sometimes low. The National Hand Hygiene Initiative in Australia aimed to improve hand hygiene compliance among healthcare workers, with the goal of reducing rates of healthcare-associated infections. Methods: We examined if the introduction of the National Hand Hygiene Initiative was associated with a change in infection rates. Monthly infection rates for six types of healthcare-associated infections were examined in 38 Australian hospitals across six states. Infection categories were: bloodstream infections, centralline associated bloodstream infections, methicillin-resistant and methicillin-sensitive Staphylococcus aureus, Staphylococcus aureus bacteraemia and surgical site infections. Results: The National Hand Hygiene Initiative was associated with a statistically significant reduction in infection rates in 11 out of 23 state and infection combinations studied. There was no change in infection rates for nine combinations, and there was an increase in three infection rates in South Australia. Conclusions: The intervention was associated with reduced infection rates in many cases. The lack of improvement in nine cases may have been because they already had effective initiatives before the national initiative’s introduction.

Systematic review of sub-microscopic P. vivax infections : prevalence and determining factors

Background Sub-microscopic (SM) Plasmodium infections represent transmission reservoirs that could jeopardise malaria elimination goals. A better understanding of the epidemiology of these infections and factors contributing to their occurrence will inform effective elimination strategies. While the epidemiology of SM P. falciparum infections has been documented, that of SM P. vivax infections has not been summarised. The objective of this study is to address this deficiency. Methodology/Principal Findings A systematic search of PubMed was conducted, and results of both light microscopy (LM) and polymerase chain reaction (PCR)-based diagnostic tests for P. vivax from 44 cross-sectional surveys or screening studies of clinical malaria suspects were analysed. Analysis revealed that SM P. vivax is prevalent across different geographic areas with varying transmission intensities. On average, the prevalence of SM P. vivax in cross-sectional surveys was 10.9%, constituting 67.0% of all P. vivax infections detected by PCR. The relative proportion of SM P. vivax is significantly higher than that of the sympatric P. falciparum in these settings. A positive relationship exists between PCR and LM P. vivax prevalence, while there is a negative relationship between the proportion of SM P. vivax and the LM prevalence for P. vivax. Amongst clinical malaria suspects, however, SM P. vivax was not identified. Conclusions/Significance SM P. vivax is prevalent across different geographic areas, particularly areas with relatively low transmission intensity. Diagnostic tools with sensitivity greater than that of LM are required for detecting these infection reservoirs. In contrast, SM P. vivax is not prevalent in clinical malaria suspects, supporting the recommended use of quality LM and rapid diagnostic tests in clinical case management. These findings enable malaria control and elimination programs to estimate the prevalence and proportion of SM P. vivax infections in their settings, and develop appropriate elimination strategies to tackle SM P. vivax to interrupt transmission.

Interventions to control nosocomial infections : study designs and statistical issues

There is a wide range of potential study designs for intervention studies to decrease nosocomial infections in hospitals. The analysis is complex due to competing events, clustering, multiple timescales and time-dependent period and intervention variables. This review considers the popular pre-post quasi-experimental design and compares it with randomized designs. Randomization can be done in several ways: randomization of the cluster [intensive care unit (ICU) or hospital] in a parallel design; randomization of the sequence in a cross-over design; and randomization of the time of intervention in a stepped-wedge design. We introduce each design in the context of nosocomial infections and discuss the designs with respect to the following key points: bias, control for nonintervention factors, and generalizability. Statistical issues are discussed. A pre-post-intervention design is often the only choice that will be informative for a retrospective analysis of an outbreak setting. It can be seen as a pilot study with further, more rigorous designs needed to establish causality. To yield internally valid results, randomization is needed. Generally, the first choice in terms of the internal validity should be a parallel cluster randomized trial. However, generalizability might be stronger in a stepped-wedge design because a wider range of ICU clinicians may be convinced to participate, especially if there are pilot studies with promising results. For analysis, the use of extended competing risk models is recommended.

Epidemiology and risk factors of oral cancer in South Africa

Head and neck cancers are some of the leading cancers in the coloured and black South African male population and the perception exists that the incidence rates are rising. Aims: To determine the standardised morbidity rates and some of the risk factors for oral cancer in South Africa. Methods: Using histologically verified data from the National Cancer Registry, the age standardised incidence rates (ASIR) and life-time risks (LR) of oral cancer in South Africa were calculated for 1988-1991.2. In an ongoing case control study (1995 +) among black patients in Johannesburg/Soweto, adjusted odds ratios for developing oral cancers in relation to tobacco and alcohol consumption were calculated. Results: Coloured males vs. females: ASIR 13.13 vs. 3.5 (/100,000/year), LR 1:65 vs. 1:244. Black males vs. females: ASIR 9.06 vs. 1.75, LR 1:86 and 1:455. White males vs. females: ASIR 8.06 vs. 3.18, LR 1:104 vs. 1:278. Asian males vs. females: ASIR 5.24 vs. 6.66, LR 1:161 vs. 1:125. The odds ratio for oral cancer in black males in relation to smoking was 7.0 (95% CI 3.0-14.6) and daily alcohol consumption 1.3 (95% CI 0.6-2.8). In black females the odds ratios in relation to smoking were 3.9 (95% CI 1.7 8.9) and daily alcohol consumption 1.7(95% CI 0.7-4.1). Conclusions: The risk factors for oral cancer in South Africa are multiple and gender discrepancies in ASIR and LR signal differences in exposure to carcinogens. It is unclear whether the incidence of oral cancers will rise in the future.

Pathogenesis of Fallopian tube damage caused by Chlamydia trachomatis infections

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide resulting in 4–5 million new cases of Chlamydia annually and an estimated 100 million cases per annum. Infections of the lower female genital tract (FGT) frequently are asymptomatic so they often remain undiagnosed or untreated. If infections are either not resolved, or are left untreated, chlamydia can ascend to the upper FGT and infect the fallopian tubes (FTs) causing salpingitis that may lead to functional damage of the FTs and tubal factor infertility (TFI). Clinical observations and experimental data have indicated a role for antibodies against C. trachomatis proteins such as the 60 kDa heat-shock protein 60 (cHSP60) in the immunopathogenesis of TFI. When released from infected cells cHSP60 can induce pro-inflammatory immune responses that may functionally impair the FTs leading to fibrosis and luminal occlusion. Chlamydial pathogenesis of irreversible and permanent tubal damage is a consequence of innate and adaptive host immune responses to ongoing or repeated infections. The extracellular matrix (ECM) that is regulated by metalloproteinases (MMPs) may also be modified by chlamydial infections of the FGT. This review will highlight protective and pathogenic immune responses to ongoing and repeated chlamydial infections of the FGT. It will also present two recent hypotheses to explain mechanisms that may contribute to FT damage during a C. trachomatis infection. If Chlamydia immunopathology can be controlled it might yield a method of inducing fibrosis and thus provide a means of non-surgical permanent contraception for women.

Risk factors for oesophageal, lung, oral and laryngeal cancers in black South Africans

The authors used data collected from 1995 to 1999, from an on-going cancer case–control study in greater Johannesburg, to estimate the importance of tobacco and alcohol consumption and other suspected risk factors with respect to cancer of the oesophagus (267 men and 138 women), lung (105 men and 41 women), oral cavity (87 men and 37 women), and larynx (51 men). Cancers not associated with tobacco or alcohol consumption were used as controls (804 men and 1370 women). Tobacco smoking was found to be the major risk factor for all of these cancers with odds ratios ranging from 2.6 (95% CI 1.5–4.5) for oesophageal cancer in female ex-smokers to 50.9 (95% CI 12.6–204.6) for lung cancer in women, and 23.9 (95% CI 9.5–60.3) for lung cancer and 23.6 (95% CI 4.6–121.2) for laryngeal cancer in men who smoked 15 or more grams of tobacco a day. This is the first time an association between smoking and oral and laryngeal cancers has been shown in sub-Saharan Africa. Long-term residence in the Transkei region in the southeast of the country continues to be a risk factor for oesophageal cancer, especially in women (odds ratio=14.7, 95% CI 4.7–46.0), possibly due to nutritional factors. There was a slight increase in lung cancer (odds ratio=2.9, 95% CI 1.1–7.5) in men working in ‘potentially noxious’ industries. ‘Frequent’ alcohol consumption, on its own, caused a marginally elevated risk for oesophageal cancer (odds ratio=1.7, 95% CI 1.0–2.9, for women and odds ratio=1.8, 95% CI 1.2–2.8, for men). The risks for oesophageal cancer in relation to alcohol consumption increased significantly in male and female smokers (odds ratio=4.7, 95% CI=2.8–7.9 in males and odds ratio=4.8, 95% CI 3.2–6.1 in females). The above results are broadly in line with international findings.