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.

Evolution to a chronic disease niche correlates with increased sensitivity to tryptophan availability for the obligate intracellular bacterium Chlamydia pneumoniae

The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge.

Self-management programs in stage 1-4 chronic kidney disease : a literature review.

Background Chronic kidney disease (CKD) is a complex health problem, which requires individuals to invest considerable time and energy in managing their health and adhering to multifaceted treatment regimens. Objectives To review studies delivering self-management interventions to people with CKD (Stages 1–4) and assess whether these interventions improve patient outcomes. Design: Systematic review. Methods Nine electronic databases (MedLine, CINAHL, EMBASE, ProQuest Health & Medical Complete, ProQuest Nursing & Allied Health, The Cochrane Library, The Joanna Briggs Institute EBP Database, Web of Science and PsycINFO) were searched using relevant terms for papers published between January 2003 and February 2013. Results The search strategy identified 2,051 papers, of which 34 were retrieved in full with only 5 studies involving 274 patients meeting the inclusion criteria. Three studies were randomised controlled trials, a variety of methods were used to measure outcomes, and four studies included a nurse on the self-management intervention team. There was little consistency in the delivery, intensity, duration and format of the self-management programmes. There is some evidence that knowledge- and health-related quality of life improved. Generally, small effects were observed for levels of adherence and progression of CKD according to physiologic measures. Conclusion The effectiveness of self-management programmes in CKD (Stages 1–4) cannot be conclusively ascertained, and further research is required. It is desirable that individuals with CKD are supported to effectively self-manage day-to-day aspects of their health.

Challenges in improving chronic disease survivorship outcomes using tele-health and self-managed online solutions

The advances in modern information and communication (ICT) technology continue to address the challenges and improve` health outcomes for the survivors of chronic disease such as prostate cancer. The management of survivorship is increasingly becoming an important need for the survivors to manage their chronic conditions. The technology interventions such as tele-health as well as self-managed technology applications have shown a potential to improve survivorship outcomes. However, the application of these tools should be supported by strong health economics evidence. This work discusses the challenges of technology led survivorship care models and presents an integrated approach to address these challenges.

Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease

Chronic kidney disease (CKD) in ageing is a burden on health systems worldwide. Rat models of age-related CKD linked with obesity and hypertension were used to investigate alterations in oxidant handling and energy metabolism to identify gene targets or markers for age-related CKD. Young adult (3 months) and old (21–24 months) spontaneously-hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar rats (normotensive, obese in ageing) were compared for renal functional and physiological parameters, renal fibrosis and inflammation, oxidative stress (hemeoxygenase-1/HO-1), apoptosis and cell injury (including Bax:Bcl-2), phosphorylated and non-phosphorylated forms of oxidant and energy sensing proteins (p66Shc, AMPK), signal transduction proteins (ERK1/2, PKB), and transcription factors (NF-κB, FoxO1). All old rats were normoglycemic. Renal fibrosis, tubular epithelial apoptosis, interstitial macrophages and myofibroblasts (all p < 0.05), p66Shc/phospho-p66 (p < 0.05), Bax/Bcl-2 ratio (p < 0.05) and NF-κB expression (p < 0.01) were highest in old obese Wistars. Expression of phospho-FoxO/FoxO was elevated in old Wistars (p < 0.001) and WKYs (p < 0.01). SHRs had high levels in young and old rats. Expression of PKB, phospho-PKB, ERK1/2 and phospho-ERK1/2 were significantly elevated in all aged animals. These results suggest that obesity and hypertension have differing oxidant handling and signalling pathways that act in the pathogenesis of age-related CKD

The long and winding road : health services for clients with chronic leg ulcers in the community

The prevalence of leg ulcers of is 0.12%–1.1% and >3,000 lower limb amputations are performed yearly in Australia due to non-healing leg or foot ulcers. Although evidence on leg ulcer management is available, a significant evidence-practice gap exists. To identify current leg ulcer management, a cross-sectional retrospective study was undertaken in Brisbane, Australia. A sample of 104 clients was recruited from a community specialist wound clinic and a tertiary hospital outpatient’s specialist wound clinic. All clients had an ulcer below their knee or on their foot for ≥4 weeks. Data were collected on ulcer care, health service usage and clinical history for the year prior to admission. On admission, participants reported having their ulcer for a median of 25 weeks (range 2-728 weeks); with 51% (53/104) reporting an ulcer duration of ≥24 weeks. Including the wound clinic, participants sought ulcer care from a median of 3 health care providers (range 2-7). General Practitioners provided ulcer care to 82% of participants. Nearly half (42%) had self-cared for their ulcer; 29% (30/104) received treatment by a community nurse. A gap was found between the community-based ulcer care experienced by this population and evidence-based guidelines in regards to assessment, management, advice, and referrals.

Poverty by acronym in Australia : welcome to CIM, VIM, PBIM, CPIM and SEAM

This paper discusses Compulsory Income Management (CIM) in Australia and the implications of technology backed forms of surveillance and increasingly conditional benefit payments. The CIM project raises important questions about requiring people to take greater responsibility for their personal behaviour when they no longer have control over key financial aspects of their lives. Some Indigenous communities have resisted the BasicsCard, because CIM was imposed with little prior consultation or subsequent independent evaluation. The compulsory income management of individuals by a paternalist welfare state contradicts and undermines the purported policy aims that they become less welfare dependent and more positively engaged with the world of paid employment and does little to address the growing condition of poverty in Australia.

Teacher education for high-poverty schools : keeping the bar high

For some time now, there has been a focus, both in Australia and internationally, on quality teaching as a fundamental component that affects the educational outcomes of all students. The question of how teacher education programs in Australia prepare effective teachers to work across all school settings-including low-SES schools-has been elevated to national prominence by data from the 20 12 Programme for International Student Assessment (PIS A), which revealed a fall in Australian students' world ranking across Mathematics, Reading and Science. Education is commonly acknowledged as a "foundation capability" that improves a person's life chances, including employment prospects, and it is widely understood to be a "route out of disadvantage" (McLachlan, Gilfillan, and Gordon 20 13). The Australian Bureau of Statistics 201 1- 12 data suggest that around 2.6 million (11.8%) Australians currently live under the poverty line (Phillips et a!. 2012, 8). According to the Organisation for Economic Cooperation and Development (OECD), despite the significant effects teachers have on student performance, disadvantaged schools are not always staffed with the highest quality teachers (see Darling-Hammond, 2006).

Nutritional support in chronic obstructive Pulmonary Disease (COPD) a randomised trial

Rationale Nutritional support is effective in managing malnutrition in COPD (Collins et al., 2012) leading to functional improvements (Collins et al., 2013). However, comparative trials of first line interventions are lacking. This randomised trial compared the effectiveness of individualised dietary advice by a dietitian (DA) versus oral nutritional supplements (ONS). Methods A target sample of 200 stable COPD outpatients at risk of malnutrition (‘MUST’; medium + high risk) were randomised to either a 12-week intervention of ONS (ONS: ~400 kcal/d, ~40 g/d protein) or DA with supportive written advice. The primary outcome was quality of life (QoL) measured using St George’s Respiratory Questionnaire with secondary outcomes including handgrip strength, body weight and nutritional intake. Both the change from baseline and the differences between groups was analysed using SPSS version 20. Results 84 outpatients were recruited (ONS: 41 vs. DA: 43), 72 completed the intervention (ONS: 33 vs. DA: 39). Mean BMI was 18.2 SD 1.6 kg/m2, age 72.6 SD 10 years, FEV1% predicted 36 SD 15% (severe COPD). In comparison to the DA group, the ONS group experienced significantly greater improvements in protein intakes above baseline values at both week 6 (+21.0 SEM 4.3 g/d vs. +0.52 SEM 4.3 g/d; p < 0.001) and week 12 (+19.0 SEM 5.0 g/d vs. +1.0 SEM 3.6 g/d; p = 0.033;ANOVA). QoL and secondary outcomes remained stable at 12 weeks in both groups with slight improvements in the ONS group but no differences between groups. Conclusion In outpatients at risk of malnutrition with severe COPD, nutritional support involving either ONS or DA appears to maintain in tritional status, functional capacity and QoL. However, larger trials, and earlier, multi-modal nutritional interventions for an extended duration should be explored.

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.

The effect of deprivation and disease-severity on malnutrition risk in chronic obstructive pulmonary disease (COPD)

Deprivation has previously been shown to be an independent risk factor for the high prevalence of malnutrition observed in COPD (Collins et al., 2010). It has been suggested the socioeconomic gradient observed in COPD is greater than any other chronic disease (Prescott & Vestbo, 1999). The current study aimed to examine the infl uence of disease severity and social deprivation on malnutrition risk in outpatients with COPD. 424 COPD outpatients were screened using the ‘Malnutrition Universal Screening Tool’ (‘MUST’). COPD disease severity was recorded in accordance with the GOLD criteria and deprivation was established according to the patient’s geographical location (postcode) at the time of nutritional screening using the UK Government’s Index of Multiple Deprivation (IMD). IMD ranks postcodes from 1 (most deprived) to 32,482 (least deprived). Disease severity was posi tively associated with an increased prevalence of malnutrition risk (p < 0.001) both within and between groups, whilst rank IMD was negatively associated with malnutrition (p = 0.020), i.e. those residing in less deprived areas were less likely to be malnourished. Within each category of disease severity the prevalence of malnutrition was two-fold greater in those residing in the most deprived areas compared to those residing in the least deprived areas. This study suggests that deprivation and disease severity are independent risk factors for malnutrition in COPD both contributing to the widely variable prevalence of malnutrition. Consideration of these issues could assist with the targeted nutritional management of these patients.

Teacher education for high poverty schools : the National Exceptional Teachers for Disadvantaged Schools program

A vital element to improve outcomes for disadvantaged students is outstanding teachers. A reality, however, is that teacher graduates in the top quartile of academic scores are far less likely to accept positions in tough urban, regional, rural and remote schools. Further, because high poverty schools can be challenging environments, these teachers are retained for much shorter periods of time. In response to this challenge, the National Exceptional Teachers for Disadvantaged Schools program (NETDS) creates a pathway for the highest quality pre-service teachers to be fully prepared, professionally and personally, for roles within high poverty schools. The program identifies the highest-achieving mainstream preservice teachers in university programs across the country and offers them a specialised curriculum and supported practicum experience in a network of disadvantaged partner schools. By working closely with government, philanthropy and partner schools, the program also works to channel these exceptional pre-service teachers into employment in schools where they will have the greatest impact. Its initial results have been exceptional: over 90% of graduates are now employed as teachers in high poverty schools. This paper will discuss their research on how they are working to build the infrastructure and capacity for research on innovations that prepare teachers for 21st century schools in the Australian context.

The Sawa World model : addressing extreme poverty through local solutions and youth empowerment

With an estimated 1.2 billion people worldwide living in extreme poverty, it is critical to find effective long-term solutions. Sawa World is a non-profit organization founded by Daphne Nederhorst in 2005 to empower marginalized youth to document simple, locally created solutions that address this pressing issue. Currently working primarily in Uganda, Sawa World has created a unique model that celebrates powerful solutions generated from within the community to help people living in poverty help themselves. Using inspiring local leaders who themselves come from extreme poverty, Sawa World aims to end extreme poverty from the ground up.

Initial burden of disease estimates for South Africa, 2000

BACKGROUND This paper describes the first national burden of disease study for South Africa. The main focus is the burden due to premature mortality, i.e. years of life lost (YLLs). In addition, estimates of the burden contributed by morbidity, i.e. the years lived with disability (YLDs), are obtained to calculate disability-adjusted life years (DALYs); and the impact of AIDS on premature mortality in the year 2010 is assessed. METHOD Owing to the rapid mortality transition and the lack of timely data, a modelling approach has been adopted. The total mortality for the year 2000 is estimated using a demographic and AIDS model. The non-AIDS cause-of-death profile is estimated using three sources of data: Statistics South Africa, the National Department of Home Affairs, and the National Injury Mortality Surveillance System. A ratio method is used to estimate the YLDs from the YLL estimates. RESULTS The top single cause of mortality burden was HIV/AIDS followed by homicide, tuberculosis, road traffic accidents and diarrhoea. HIV/AIDS accounted for 38% of total YLLs, which is proportionately higher for females (47%) than for males (33%). Pre-transitional diseases, usually associated with poverty and underdevelopment, accounted for 25%, non-communicable diseases 21% and injuries 16% of YLLs. The DALY estimates highlight the fact that mortality alone underestimates the burden of disease, especially with regard to unintentional injuries, respiratory disease, and nervous system, mental and sense organ disorders. The impact of HIV/AIDS is expected to more than double the burden of premature mortality by the year 2010. CONCLUSION This study has drawn together data from a range of sources to develop coherent estimates of premature mortality by cause. South Africa is experiencing a quadruple burden of disease comprising the pre-transitional diseases, the emerging chronic diseases, injuries, and HIV/AIDS. Unless interventions that reduce morbidity and delay morbidity become widely available, the burden due to HIV/AIDS can be expected to grow very rapidly in the next few years. An improved base of information is needed to assess the morbidity impact more accurately.

Predictors of chronic bronchitis in South African adults

SETTING National household survey of adults in South Africa, a middle income country. OBJECTIVE To determine the prevalence and predictors of chronic bronchitis. DESIGN A stratified national probability sample of households was selected. All adults in the selected households were interviewed. Chronic bronchitis was defined as chronic productive cough. Socio-demographic predictors were wealth, education, race, age and urban residence. Personal and exposure variables included history of tuberculosis, domestic exposure to smoky fuels, occupational exposures, smoking and body mass index. RESULTS The overall prevalence of chronic bronchitis was 2.3% in men and 2.8% in women. The strongest predictor of chronic bronchitis was a history of tuberculosis (men, odds ratio [OR] 4.9; 95% confidence interval [CI] 2.6-9.2; women, OR 6.6; 95% CI 3.7-11.9). Other risk factors were smoking, occupational exposure (in men), domestic exposure to smoky fuel (in women) and (in univariate analysis only) being underweight. Wealth and particularly education were protective. CONCLUSION The pattern of chronic bronchitis in South Africa suggests a combination of risk factors that includes not only smoking but also tuberculosis, occupational exposures in men and domestic fuel exposure in women. Control of these risk factors requires public health action across a broad front. The protective role of education requires elucidation.