Amphiphilic block copolymer nanoparticles are conjugated with uropathogenic Escherichia coli type 1 pilus adhesin FimHA through amidation chemistry to enable bladder epithelial cell binding and internalization of the nanoparticles in vitro.
To determine prevalence and incidence of bacterial vaginosis (BV) and risk factors in young sexually-active Australian women.
1093 women aged 16–25 years were recruited from primary-care clinics. Participants completed 3-monthly questionnaires and self-collected vaginal smears 6-monthly for 12-months. The primary endpoint was a Nugent Score = 7–10 (BV) and the secondary endpoint was a NS = 4–10 (abnormal flora [AF]). BV and AF prevalence estimates and 95% confidence intervals (95%CI) were derived, and adjusted odds ratios (AOR) calculated to explore epidemiological associations with prevalent BV and AF. Proportional-hazards regression models were used to examine factors associated with incident BV and AF.
At baseline 129 women had BV [11.8% (95%CI: 9.4–14.2)] and 188 AF (17.2%; 15.1–19.5). Prevalent BV was associated with having a recent female partner [AOR = 2.1; 1.0–4.4] and lack of tertiary-education [AOR = 1.9; 1.2–3.0]; use of an oestrogen-containing contraceptive (OCC) was associated with reduced risk [AOR = 0.6; 0.4–0.9]. Prevalent AF was associated with the same factors, and additionally with >5 male partners (MSP) in 12-months [AOR = 1.8; 1.2–2.5)], and detection of C.trachomatis or M.genitalium [AOR = 2.1; 1.0–4.5]. There were 82 cases of incident BV (9.4%;7.7–11.7/100 person-years) and 129 with incident AF (14.8%; 12.5–17.6/100 person-years). Incident BV and AF were associated with a new MSP [adjusted rate ratio (ARR) = 1.5; 1.1–2.2 and ARR = 1.5; 1.1–2.0], respectively. OCC-use was associated with reduced risk of incident AF [ARR = 0.7; 0.5–1.0].
This paper presents BV and AF prevalence and incidence estimates from a large prospective cohort of young Australian women predominantly recruited from primary-care clinics. These data support the concept that sexual activity is strongly associated with the development of BV and AF and that use of an OCC is associated with reduced risk.
In many countries, low Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) screening rates among young people in primary-care have encouraged screening programs outside of clinics. Nucleic acid amplification tests (NAATs) make it possible to screen people in homes with self-collected specimens. We systematically reviewed the strategies and outcomes of home-based CT/NG screening programs.
Electronic databases were searched for home-based CT and/or NG screening studies published since January 2005. Screening information (e.g. target group, recruitment and specimen-collection method) and quantitative outcomes (e.g. number of participants, tests and positivity) were extracted. The screening programs were classified into seven groups on the basis of strategies used.
We found 29 eligible papers describing 32 home-based screening programs. In seven outreach programs, people were approached in their homes: a median of 97% participants provided specimens and 76% were tested overall (13717 tests). In seven programs, people were invited to receive postal test-kits (PTKs) at their homes: a median of 37% accepted PTKs, 79% returned specimens and 19% were tested (46225 tests). PTKs were sent along with invitation letters in five programs: a median of 33% returned specimens and 29% of those invited were tested (15126 tests). PTKs were requested through the internet or phone without invitations in four programs and a median of 32% returned specimens (2666 tests). Four programs involved study personnel directly inviting people to receive PTKs: a median of 46% accepted PTKs, 21% returned specimens and 9.1% were tested (341 tests). PTKs were picked-up from designated locations in three programs: a total of 6765 kits were picked-up and 1167 (17%) specimens were returned for screening. Two programs used a combination of above strategies (2395 tests) but the outcomes were not reported separately. The overall median CT positivity was 3.6% (inter-quartile range: 1.7-7.3%).
A variety of strategies have been used in home-based CT/NG screening programs. The screening strategies and their feasibility in the local context need to be carefully considered to maximize the effectiveness of home-based screening programs.
Sexually transmitted infections; Chlamydia trachomatis; Screening; Home
Nuocytes are essential in innate type-2 immunity and contribute to the exacerbation of asthma responses. Here we show that nuocytes arise in the bone marrow and differentiate from common lymphoid progenitors, which makes them distinct new members of the lymphoid lineage. Nuocytes required interleukin 7 (IL-7), IL-33 and Notch signalling for development in vitro. Double negative 1 (DN1) and DN2 pro-T-cell progenitors maintained nuocyte potential in vitro, although the thymus was not essential for nuocyte development. Notably, the transcription factor Rorα was critical for nuocyte development and their role in parasitic worm expulsion.
The ubiquitously expressed phosphatidylinositol binding clathrin assembly (PICALM) protein associates with the plasma membrane, binds clathrin, and plays a role in clathrin-mediated endocytosis. Alterations of the human PICALM gene are present in aggressive hematopoietic malignancies, and genome-wide association studies have recently linked the PICALM locus to late-onset Alzheimer's disease. Inactivating and hypomorphic Picalm mutations in mice cause different degrees of severity of anemia, abnormal iron metabolism, growth retardation and shortened lifespan. To understand PICALM’s function, we studied the consequences of PICALM overexpression and characterized PICALM-deficient cells derived from mutant fit1 mice. Our results identify a role for PICALM in transferrin receptor (TfR) internalization and demonstrate that the C-terminal PICALM residues are critical for its association with clathrin and for the inhibitory effect of PICALM overexpression on TfR internalization. Murine embryonic fibroblasts (MEFs) that are deficient in PICALM display several characteristics of iron deficiency (increased surface TfR expression, decreased intracellular iron levels, and reduced cellular proliferation), all of which are rescued by retroviral PICALM expression. The proliferation defect of cells that lack PICALM results, at least in part, from insufficient iron uptake, since it can be corrected by iron supplementation. Moreover, PICALM-deficient cells are particularly sensitive to iron chelation. Taken together, these data reveal that PICALM plays a critical role in iron homeostasis, and offer new perspectives into the pathogenesis of PICALM-associated diseases.
To examine the association of social and environmental factors with levels of second hand smoke (SHS) exposure, as measured by salivary cotinine, in young inner city children with asthma.
We used data drawn from a home-based behavioral intervention for young high risk children with persistent asthma post emergency department (ED) treatment (N=198). SHS exposure was measured by salivary cotinine and caregiver report. Caregiver demographic and psychological functioning, household smoking behavior and asthma morbidity were compared with child cotinine concentrations. Chi-square and ANOVA tests and multivariate regression models were used to determine the association between cotinine concentrations with household smoking behavior and asthma morbidity.
Over half (53%) of the children had cotinine levels compatible with SHS exposure and mean cotinine concentrations were high at 2.42 ng/ml (SD 3.2). The caregiver was the predominant smoker in the home (57%) and (63%) reported a total home smoking ban. Preschool age children, and those with caregivers reporting depressive symptoms and high stress had higher cotinine concentrations than their counterparts. Among children living in a home with a total home smoking ban, younger children had significantly higher mean cotinine concentration than older children (Cotinine: 3–5 year olds, 2.24 ng/ml (SD 3.5); 6–10 year olds, 0.63 ng/ml (SD 1.0); p <0.05). In multivariate models, the factors most strongly associated with high child cotinine concentrations were increased number of household smokers (β = 0.24) and younger child age (3–5 years) (β = 0.23; P <0.001, R2 = 0.35).
Over half of young inner-city children with asthma were exposed to second hand smoke and caregivers are the predominant household smoker. Younger children and children with depressed and stressed caregivers are at significant risk of smoke exposures, even when a household smoking ban is reported. Further advocacy for these high-risk children is needed to help caregivers quit and to mitigate smoke exposure.
asthma; children; cotinine; second hand smoke
This study aimed to estimate rates of chlamydia incidence and re-infection and to investigate the dynamics of chlamydia organism load in prevalent, incident and re-infections among young Australian women.
1,116 women aged 16 to 25 years were recruited from primary care clinics in Australia. Vaginal swabs were collected at 3 to 6 month intervals for chlamydia testing. Chlamydia organism load was measured by quantitative PCR.
There were 47 incident cases of chlamydia diagnosed and 1,056.34 person years of follow up with a rate of 4.4 per 100 person years (95% CI: 3.3, 5.9). Incident infection was associated with being aged 16 to 20 years [RR = 3.7 (95%CI: 1.9, 7.1)], being employed [RR = 2.4 (95%CI: 1.1, 4.9)] and having two or more new sex partners [RR = 5.5 (95%CI: 2.6, 11.7)]. Recent antibiotic use was associated with a reduced incidence [RR:0.1 (95%CI: 0.0, 0.5)]. There were 14 re-infections with a rate of 22.3 per 100 person years (95%CI: 13.2, 37.6). The median time to re-infection was 4.6 months. Organism load was higher for prevalent than incident infections (p<0.01) and for prevalent than re-infections (p<0.01).
Chlamydia is common among young women and a high proportion of women are re-infected within a short period of time, highlighting the need for effective partner treatment and repeat testing. The difference in organism load between prevalent and incident infections suggests prevalent infection may be more important for ongoing transmission of chlamydia.
We developed a high speed voice coil based whisker stimulator that delivers precise deflections of a single whisker or group of whiskers in a repeatable manner. The device is miniature, quiet, and inexpensive to build. Multiple stimulators fit together for independent stimulation of four or more whiskers. The system can be used with animals under anesthesia as well as awake animals with head-restraint, and does not require trimming the whiskers. The system can deliver 1–2 mm deflections in 2 ms resulting in velocities up to 900 mm/s to attain a wide range of evoked responses. Since auditory artifacts can influence behavioral studies using whisker stimulation, we tested potential effects of auditory noise by recording somatosensory evoked potentials (SEP) with varying auditory click levels, and with/without 80 dBa background white noise. We found that auditory clicks as low as 40 dBa significantly influence the SEP. With background white noise, auditory clicks as low as 50 dBa were still detected in components of the SEP. For behavioral studies where animals must learn to respond to whisker stimulation, these sounds must be minimized. Together, the stimulator and data system can be used for psychometric vigilance tasks, mapping of the barrel cortex and other electrophysiological paradigms.
evoked response; voice coil; rodent; vibrissae; auditory
Investigations into the physiological mechanisms of sleep control require an animal psychomotor vigilance task (PVT) with fast response times (<300ms). Rats provide a good PVT model since whisker stimulation produces a rapid and robust cortical evoked response, and animals can be trained to lick following stimulation. Our prior experiments used deprivation-based approaches to maximize motivation for operant conditioned responses. However, deprivation can influence physiological and neurobehavioral effects. In order to maintain motivation without water deprivation, we conditioned rats for immobilization and head restraint, then trained them to lick for a 10% sucrose solution in response to whisker stimulation. After approximately 8 training sessions, animals produced greater than 80% correct hits to the stimulus. Over the course of training, reaction times became faster and correct hits increased. Performance in the PVT was examined after 3, 6 and 12 hours of sleep deprivation achieved by gentle handling. A significant decrease in percent correct hits occurred following 6 and 12 hours of sleep deprivation and reaction times increased significantly following 12 hours of sleep deprivation. While behaviorally the animals appeared to be awake, we observed significant increases in EEG delta power prior to misses. The rat PVT with fast response times allows investigation of sleep deprivation effects, time on task and pharmacological agents. Fast response times also allow closer parallel studies to ongoing human protocols.
PVT; restraint; conditioned learning; lick; somatosensory cortex; electrophysiology; sleep deprivation; reaction time
The ability of the opportunistic pathogen, Staphylococcus aureus, to form biofilms is increasingly being viewed as an important contributor to chronic infections. In vitro methods for analyzing S. aureus biofilm formation have focused on bacterial attachment and accumulation on abiotic surfaces, such as in microtiter plate and flow cell assays. Microtiter plates provide a rapid measure of relative biomass levels, while flow cells have limited experimental throughput but are superior for confocal microscopy biofilm visualization. Although these assays have proven effective at identifying mechanisms involved in cell attachment and biofilm accumulation, the significance of these assays in vivo remains unclear. Studies have shown that when medical devices are implanted they are coated with host factors, such as matrix proteins, that facilitate S. aureus attachment and biofilm formation. To address the challenge of integrating existing biofilm assay features with a biotic surface, we have established an in vitro biofilm technique utilizing UV-sterilized coverslips coated with human plasma. The substratum more closely resembles the in vivo state and provides a platform for S. aureus to establish a robust biofilm. Importantly, these coverslips are amenable to confocal microscopy imaging to provide a visual reference of the biofilm growth stage, effectively merging the benefits of the microtiter and flow cell assays. We confirmed the approach using clinical S. aureus isolates and mutants with known biofilm phenotypes. Altogether, this new biofilm assay can be used to assess the function of S. aureus virulence factors associated with biofilm formation and for monitoring the efficacy of biofilm treatment modalities.
Staphylococcus aureus; MRSA; biofilm; assay
Llama derived single domain antibodies (sdAb), the recombinantly expressed variable heavy domains from the unique heavy-chain only antibodies of camelids, were isolated from a library derived from llamas immunized with a commercial abrin toxoid preparation. Abrin is a potent toxin similar to ricin in structure, sequence and mechanism of action. The selected sdAb were evaluated for their ability to bind to commercial abrin as well as abrax (a recombinant abrin A-chain), purified abrin fractions, Abrus agglutinin (a protein related to abrin but with lower toxicity), ricin, and unrelated proteins. Isolated sdAb were also evaluated for their ability to refold after heat denaturation and ability to be used in sandwich assays as both capture and reporter elements. The best binders were specific for the Abrus agglutinin, showing minimal binding to purified abrin fractions or unrelated proteins. These binders had sub nM affinities and regained most of their secondary structure after heating to 95 °C. They functioned well in sandwich assays. Through gel analysis and the behavior of anti-abrin monoclonal antibodies, we determined that the commercial toxoid preparation used for the original immunizations contained a high percentage of Abrus agglutinin, explaining the selection of Abrus agglutinin binders. Used in conjunction with anti-abrin monoclonal and polyclonal antibodies, these reagents can fill a role to discriminate between the highly toxic abrin and the related, but much less toxic, Abrus agglutinin and distinguish between different crude preparations.
abrin; single domain antibody; reversible refolding
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Recent studies suggest that pericardial adipose tissue (PCAT) secretes inflammatory factors that contribute to the development of CVD. To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between PCAT and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. As it was unknown whether PCAT-secreted factors are produced by adipocytes or cells in the supporting stromal fraction, we also sought to identify differentially expressed genes in isolated pericardial adipocytes vs. isolated subcutaneous adipocytes. Using microarray analysis, we found that: 1) pericardial adipose tissue and isolated pericardial adipocytes both overexpress atherosclerosis-promoting chemokines and 2) pericardial and subcutaneous fat depots, as well as isolated pericardial adipocytes and subcutaneous adipocytes, express specific patterns of homeobox genes. In contrast, a core set of lipid processing genes showed no significant overlap with differentially expressed transcripts. These depot-specific homeobox signatures and transcriptional profiles strongly suggest different functional roles for the pericardial and subcutaneous adipose depots. Further characterization of these inter-depot differences should be a research priority.
Depressive symptoms in alcohol-dependent individuals are well recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol-induced. In order to contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin releasing factor (CRF) levels in specific brain regions. Adult male Wistar rats were subjected to intermittent ethanol vapor (14 hours on / 10 hours off) or air exposure for two weeks and were then tested at three time points corresponding to acute withdrawal (8–12 hours into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five minute FST consisted of latency to immobility, swim time, immobility time and climbing time. The FST results showed that the vapor-exposed animals displayed depressive-like behaviors, for instance decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60 day withdrawal period. NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared to the control animals and CRF levels in the amygdala were correlated with increased immobility time. Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain.
Alcohol; CRF; Dependence; Depression; Forced Swim Test; NPY
Established in-house quantitative PCR (qPCR) assays to detect the Mycoplasma genitalium adhesion protein (MgPa) and the 16S rRNA gene were found to be comparable for screening purposes, with a kappa value of 0.97 (95% confidence interval [CI], 0.94 to 1.01) and no difference in bacterial load quantified (P = 0.4399).
To determine whether chlamydia positivity among heterosexual men (MSW) and chlamydia and gonorrhea positivity among men who have sex with men (MSM), are changing.
Computerized records for men attending a large sexual health clinic between 2002 and 2009 were analyzed. Chlamydia and gonorrhea positivity were calculated and logistic regression used to assess changes over time.
17769 MSW and 8328 MSM tested for chlamydia and 7133 MSM tested for gonorrhea. In MSW, 7.37% (95% CI: 6.99-7.77) were chlamydia positive; the odds of chlamydia positivity increased by 4% per year (OR = 1.04; 95% CI: 1.01-1.07; p = 0.02) after main risk factors were adjusted for. In MSM, 3.70% (95% CI: 3.30-4.14) were urethral chlamydia positive and 5.36% (95% CI: 4.82-5.96) were anal chlamydia positive; positivity could not be shown to have changed over time. In MSM, 3.05% (95% CI: 2.63-3.53) tested anal gonorrhea positive and 1.83% (95% CI: 1.53-2.18) tested pharyngeal gonorrhea positive. Univariate analysis found the odds of anal gonorrhea positivity had decreased (OR = 0.93; 95% CI: 0.87-1.00; p = 0.05), but adjusting for main risk factors resulted in no change. Urethral gonorrhea cases in MSM as a percentage of all MSM tested for gonorrhea also fell (p < 0.001).
These data suggest that chlamydia prevalence in MSW is rising and chlamydia and gonorrhea prevalence among MSM is stable or declining. High STI testing rates among MSM in Australia may explain differences in STI trends between MSM and MSW.
Chlamydia; Gonorrhea; Men who have sex with men; Heterosexual men; Positivity
Care transitions are a common and frequently adverse aspect of health care, resulting in a high-risk period for both care quality and patient safety. Patients who have complex care needs and undergo treatment in multiple care settings, such as older patients with musculoskeletal disorders, may be at higher risk for poor care transitions.
Key informant interviews were used to gather in-depth information on transitional care issues, particularly those which impact informational continuity, from the perspective of a range of health professionals (η=17) in care settings relevant to the care continuum of older patients with hip fractures.
Three transitional care themes were identified; medical complexity impacts care trajectories, larger circles of care can be both beneficial and challenging, and a variety of channels and modes are required for meaningful information exchange. Many issues cut across each care setting, and address challenges to informational continuity among and between health care providers, patients, and caregivers.
Medical complexity enlarges the circle of care which challenges care continuity. There may be fundamental elements which, regardless of care setting, strengthen transitional care quality. Standardized transitional care processes might help to offset informational discontinuity across care settings as a result of this population’s larger circles of care.
care transitions; musculoskeletal disorder; information exchange; care continuity
Cohort studies are an important study design however they are difficult to implement, often suffer from poor retention, low participation and bias. The aims of this paper are to describe the methods used to recruit and retain young women in a longitudinal study and to explore factors associated with loss to follow up.
The Chlamydia Incidence and Re-infection Rates Study (CIRIS) was a longitudinal study of Australian women aged 16 to 25 years recruited from primary health care clinics. They were followed up via the post at three-monthly intervals and required to return questionnaires and self collected vaginal swabs for chlamydia testing. The protocol was designed to maximise retention in the study and included using recruiting staff independent of the clinic staff, recruiting in private, regular communication with study staff, making the follow up as straightforward as possible and providing incentives and small gifts to engender good will.
The study recruited 66% of eligible women. Despite the nature of the study (sexual health) and the mobility of the women (35% moved address at least once), 79% of the women completed the final stage of the study after 12 months. Loss to follow up bias was associated with lower education level [adjusted hazard ratio (AHR): 0.7 (95% Confidence Interval (CI): 0.5, 1.0)], recruitment from a sexual health centre as opposed to a general practice clinic [AHR: 1.6 (95% CI: 1.0, 2.7)] and previously testing positive for chlamydia [AHR: 0.8 (95% CI: 0.5, 1.0)]. No other factors such as age, numbers of sexual partners were associated with loss to follow up.
The methods used were considered effective for recruiting and retaining women in the study. Further research is needed to improve participation from less well-educated women.
Differences in the determinants of Chlamydia trachomatis ('chlamydia') and Mycoplasma genitalium (MG) genital infection in women are not well understood.
A cohort study of 16 to 25 year old Australian women recruited from primary health care clinics, aimed to determine chlamydia and MG prevalence and incidence. Vaginal swabs collected at recruitment were used to measure chlamydia and MG prevalence, organism-load and chlamydia-serovar a cross-sectional analysis undertaken on the baseline results is presented here.
Of 1116 participants, chlamydia prevalence was 4.9% (95% CI: 2.9, 7.0) (n = 55) and MG prevalence was 2.4% (95% CI: 1.5, 3.3) (n = 27). Differences in the determinants were found - chlamydia not MG, was associated with younger age [AOR:0.9 (95% CI: 0.8, 1.0)] and recent antibiotic use [AOR:0.4 (95% CI: 0.2, 1.0)], and MG not chlamydia was associated with symptoms [AOR:2.1 (95% CI: 1.1, 4.0)]. Having two or more partners in last 12 months was more strongly associated with chlamydia [AOR:6.4 (95% CI: 3.6, 11.3)] than MG [AOR:2.2 (95% CI: 1.0, 4.6)] but unprotected sex with three or more partners was less strongly associated with chlamydia [AOR:3.1 (95%CI: 1.0, 9.5)] than MG [AOR:16.6 (95%CI: 2.0, 138.0)]. Median organism load for MG was 100 times lower (5.7 × 104/swab) than chlamydia (5.6 × 106/swab) (p < 0.01) and not associated with age or symptoms for chlamydia or MG.
These results demonstrate significant chlamydia and MG prevalence in Australian women, and suggest that the differences in strengths of association between numbers of sexual partners and unprotected sex and chlamydia and MG might be due to differences in the transmission dynamics between these infections.
Despite well-documented evidence that physical activity is beneficial to children, average fitness levels of US children have declined. Lack of physical activity has been associated with childhood obesity. We evaluated the effects of a physical activity program in the elementary school classroom on health outcomes.
Three schools in the Independence School District in Independence, Missouri, were assigned to receive the ABC (Activity Bursts in the Classroom) for Fitness program, and 2 comparable schools served as controls. The program, led by classroom teachers, provides multiple, brief, structured physical activity breaks throughout the day. Baseline data for the study were collected in September 2007, and follow-up data were collected in April 2008.
Physical fitness measures of upper-body strength, abdominal strength, and trunk extensor improved (P <.001). Medication use for asthma (P = .03), attention-deficit hyperactivity disorder (P = .07), or either medication combined (P = .005) decreased.
The effects of the program on daily physical activity, fitness, and measures of health are beneficial.
Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type 1 pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1–dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1 pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1 pili endows unique anti-biofilm and anti-virulence activities on these compounds.
The transitional epithelium of the bladder normally turns over slowly but, upon injury, undergoes rapid regeneration, fueled by basal uroepithelial stem and/or early progenitor cells (USCs). Little is known about the mechanisms underlying the injury response. Here, we investigate the mechanism of bladder epithelial regeneration in response to infection with uropathogenic E. coli (UPEC). We show that infection resulted in rapid sloughing of superficial cells, a marked inflammatory response, and a substantial spike in basal cell proliferation. Epithelial renewal following infectious injury was mediated in part by Bmp signaling. In mice with Cre-recombinase-mediated ablation of the Bmp4 receptor, Bmpr1a, infection leads to aberrant urothelial renewal resulting in a block in USC differentiation into superficial cells. The response to chemical injury with protamine sulfate (PS) also caused sloughing but no inflammation or USC activation. Together, our study indicates that UPEC infection activates the USC niche, and Bmp signaling is required for regulation of the USC response to infection.
bladder; Bmp4; bone morphogenetic protein; uropathogenic E. coli; injury; repair; stem cell; niche; urinary tract infections; interstitial cystitis; urothelium
Financial incentives have been used for many years internationally to improve quality of care in general practice. The aim of this pilot study was to determine if offering general practitioners (GP) a small incentive payment per test would increase chlamydia testing in women aged 16 to 24 years, attending general practice.
General practice clinics (n = 12) across Victoria, Australia, were cluster randomized to receive either a $AUD5 payment per chlamydia test or no payment for testing 16 to 24 year old women for chlamydia. Data were collected on the number of chlamydia tests and patient consultations undertaken by each GP over two time periods: 12 month pre-trial and 6 month trial period. The impact of the intervention was assessed using a mixed effects logistic regression model, accommodating for clustering at GP level.
Testing increased from 6.2% (95% CI: 4.2, 8.4) to 8.8% (95% CI: 4.8, 13.0) (p = 0.1) in the control group and from 11.5% (95% CI: 4.6, 18.5) to 13.4% (95% CI: 9.5, 17.5) (p = 0.4) in the intervention group. Overall, the intervention did not result in a significant increase in chlamydia testing in general practice. The odds ratio for an increase in testing in the intervention group compared to the control group was 0.9 (95% CI: 0.6, 1.2). Major barriers to increased chlamydia testing reported by GPs included a lack of time, difficulty in remembering to offer testing and a lack of patient awareness around testing.
A small financial incentive alone did not increase chlamydia testing among young women attending general practice. It is possible small incentive payments in conjunction with reminder and feedback systems may be effective, as may higher financial incentive payments. Further research is required to determine if financial incentives can increase testing in Australian general practice, the type and level of financial scheme required and whether incentives needs to be part of a multi-faceted package.
Australian New Zealand Clinical Trial Registry ACTRN12608000499381.
Among rural children with asthma and their parents, this study examined the relationship between parental and child reports of quality of life and described the relationship of several factors such as asthma severity, missed days of work and asthma education on their quality of life.
Two hundred and one rural families with asthma were enrolled in a school-based educational program. Intervention parents and children received interactive asthma workshop(s), asthma devices and literature. Parent and child quality of life measurements were obtained pre and post intervention using Juniper's Paediatric Caregivers Quality of Life and Juniper's Paediatric Quality of Life Questionnaires. Asthma severity was measured using criteria from the National Asthma Education and Prevention Program (NAEPP) guidelines.
There was no association between parent and child total quality of life scores, and mean parental total quality of life scores were higher at baseline and follow-up than those of the children. All the parents' quality of life scores were correlated with parental reports of missed days of work. For all children, emotional quality of life (EQOL) was significantly associated with parental reports of school days missed (p= .03) and marginally associated with parental reports of hospitalizations due to asthma (p=.0.08). Parent's emotional quality of life (EQOL) and activity quality of life (AQOL) were significantly associated with children's asthma severity (EQOL, p=.009, AQOL, p=0.03), but not the asthma educational intervention. None of the child quality of life measurements were associated with asthma severity.
Asthma interventions for rural families should help families focus on gaining and maintaining low asthma severity levels in order for families to enjoy an optimal quality of life. Health care providers should try to assess the child's quality of life at each asthma care visit independently of the parents.
The heterogeneity evident among home care clients highlights the need for greater understanding of the clinical and social determinants of multi-dimensional health-related quality of life (HRQL) indices and of potential sex-differences in these determinants. We examined the relative contribution of social and clinical factors to HRQL among older home care clients and explored whether any of the observed associations varied by sex.
The Canadian-US sample included 514 clients. Self-reported HRQL was measured during in-home interviews (2002-04) using the Health Utilities Index Mark 2 (HUI2). Data on clients' sociodemographic, health and clinical characteristics were obtained with the Minimum Data Set for Home Care. The relative associations between clients' characteristics and HUI2 scores were examined using multivariable linear regression models.
Women had a significantly lower mean HUI2 score than men (0.48, 95%CI 0.46-0.50 vs. 0.52, 0.49-0.55). Clients with distressed caregivers and poor self-rated health exhibited significantly lower HRQL scores after adjustment for a comprehensive list of clinical conditions. Several other factors remained statistically significant (arthritis, psychiatric illness, bladder incontinence, urinary tract infection) or clinically important (reported loneliness, congestive heart failure, pressure ulcers) correlates of lower HUI2 scores in adjusted analyses. These associations generally did not vary significantly by sex.
For females and males, HRQL scores were negatively associated with conditions predictive or indicative of disability and with markers of psychosocial stress. Despite sex differences in the prevalence of social and clinical factors likely to affect HRQL, few varied significantly by sex in their relative impact on HUI2 scores. Further exploration of differences in the relative importance of clinical and psychosocial well-being (e.g., loneliness) to HRQL among female and male clients may help guide the development of sex-specific strategies for risk screening and care management.