Exploring the healthcare experiences and quality of life of people with mild cognitive impairment and their caregivers

Mild cognitive impairment (MCI) is a common condition which lies between normal cognition and dementia. Relatively little is known about the experiences of people with MCI (PWMCI) and their caregivers (‘advocates’), particularly regarding healthcare services. No measures developed specifically to evaluate health related quality of life in PWMCI or their advocates exist. Therefore the aim of this work was to gather information about these groups’ experiences of living with MCI, with particular reference to their contact with healthcare services, to use this information to develop a patient reported outcome measure (PROM) for PWMCI and equivalent measure for advocates and to suggest improvements to healthcare services in light of the findings. Initial, in-depth information was gathered during semi-structured interviews with 23 PWMCI and 20 linked advocates, the resulting data was analysed using grounded theory methods. Commonly recurring and salient themes from analysis of the interview data were used as a basis for initial drafts of the outcome measures and patient and advocate surveys regarding healthcare experiences. The outcome measures and healthcare surveys were combined into two questionnaires (one for PWMCI and one for advocates). These initial drafts were discussed with a focus group and refined in light of their feedback, the resulting questionnaires were administered (by post) to 280 PWMCI (recruited from research databases and memory clinics) and their linked advocates. The response rate was 54% for PWMCI and 36% for advocates. Data from the outcome measure section of the questionnaire was analysed using factor analysis producing a measure for PWMCI (the MCQ) and one for advocates (the MCQ-Carer); both had good psychometric properties. Descriptive analysis of the healthcare experiences survey data revealed that both the PWMCI and advocates reported a range of unmet needs for help, support and information related to MCI; appropriate suggested improvements to healthcare services are made

Health benefits from nature experiences depend on dose

Nature within cities will have a central role in helping address key global public health 3 challenges associated with urbanization. However, there is almost no guidance on how much 4 or how frequently people need to engage with nature, and what types or characteristics of 5 nature need to be incorporated in cities for the best health outcomes. Here we use a nature 6 dose framework to examine the associations between the duration, frequency and intensity of 7 exposure to nature and health in an urban population. We show that people who made long 8 visits to green spaces had lower rates of depression and high blood pressure, and those who 9 visited more frequently had greater social cohesion. Higher levels of physical activity were 10 linked to both duration and frequency of green space visits. A dose-response analysis for 11 depression and high blood pressure suggest that visits to outdoor green spaces of 30 minutes 12 or more during the course of a week could reduce the population prevalence of these illnesses 13 by up to 7% and 9% respectively. Given that the societal costs of depression alone in 14 Australia are estimated at AUD$12.6 billion per annum, savings to public health budgets 15 across all health outcomes could be immense.D.F.S. is supported through ARC Discovery Grant DP120102857 and the Centre of Excellence for Environmental Decisions (CEED, Australia); R.A.F. holds an ARC Future Fellowship; B.B.L. is supported through the CSIRO Land and Water Flagship; and K.J.G. is supported by NERC grant NE/J015237/1. J. Rhodes, K. Johansen and S. Wu contributed to the development of the vegetation data. Authors would like to thank the Brisbane City Council for providing GIS data layers, the Department of Science, Information Technology and Innovation and the Department of Natural Resources and Mines, QLD for providing access to the airborne LiDAR

Less-healthy eating behaviors have a greater association with a high level of sugar-sweetened beverage consumption among rural adults than among urban adults

Background: Sugar-sweetened beverage (SSB) consumption is associated with the increasing prevalence of overweight and obesity in the United States; however, little is known about how less-healthy eating behaviors influence high levels of SSB consumption among rural adults. Objective: We assessed the frequency of SSB consumption among rural and urban adults, examined the correlates of frequent SSB consumption, and determined difference in correlates between rural and urban adults in a large region of Texas. Design: A cross-sectional study using data on 1,878 adult participants (urban = 734 and rural = 1,144), who were recruited by random digit dialing to participate in the seven-county 2006 Brazos Valley Community Health Assessment. Data included demographic characteristics, eating behaviors (SSB consumption, frequency of fast-food meals, frequency of breakfast meals, and daily fruit and vegetable intake), and household food insecurity. Results: The prevalence of any consumption of SSB and the prevalence of high consumption of SSB were significantly higher among rural adults compared with urban counterparts. The multivariable logistic regression models indicated that a high level of SSB consumption (≥3 cans or glasses SSB/day) was associated with demographic characteristics (poverty-level income and children in the home), frequent consumption of fast-food meals, infrequent breakfast meals, low fruit and vegetable intake, and household food insecurity especially among rural adults. Conclusions: This study provides impetus for understanding associations among multiple eating behaviors, especially among economically and geographically disadvantaged adults. New strategies are needed for educating consumers, not only about how to moderate their SSB intake, but also how to simultaneously disrupt the co-occurrence of undesirable eating and promote healthful eating

Revisiting the symptom iceberg in today's primary care: results from a UK population survey

Peer reviewedPublisher PD

False negative results from using common PCR reagents

Background\ud The sensitivity of the PCR reaction makes it ideal for use when identifying potentially novel viral infections in human disease. Unfortunately, this same sensitivity also leaves this popular technique open to potential contamination with previously amplified PCR products, or "carry-over" contamination. PCR product carry-over contamination can be prevented with uracil-DNA-glycosylase (UNG), and it is for this reason that it is commonly included in many commercial PCR master-mixes. While testing the sensitivity of PCR assays to detect murine DNA contamination in human tissue samples, we inadvertently discovered that the use of this common PCR reagent may lead to the production of false-negative PCR results.\ud \ud Findings\ud We show here that contamination with minute quantities of UNG-digested PCR product or any negative control PCR reactions containing primer-dimers regardless of UNG presence can completely block amplification from as much as 60 ng of legitimate target DNA.\ud \ud Conclusions\ud These findings could potentially explain discrepant results from laboratories attempting to amplify MLV-related viruses including XMRV from human samples, as none of the published reports used internal-tube controls for amplification. The potential for false negative results needs to be considered and carefully controlled in PCR experiments, especially when the target copy number may be low - just as the potential for false positive results already is

Rac1 Is Required for Pathogenicity and Chm1-Dependent Conidiogenesis in Rice Fungal Pathogen Magnaporthe grisea

Rac1 is a small GTPase involved in actin cytoskeleton organization and polarized cell growth in many organisms. In this study, we investigate the biological function of MgRac1, a Rac1 homolog in Magnaporthe grisea. The Mgrac1 deletion mutants are defective in conidial production. Among the few conidia generated, they are malformed and defective in appressorial formation and consequently lose pathogenicity. Genetic complementation with native MgRac1 fully recovers all these defective phenotypes. Consistently, expression of a dominant negative allele of MgRac1 exhibits the same defect as the deletion mutants, while expression of a constitutively active allele of MgRac1 can induce abnormally large conidia with defects in infection-related growth. Furthermore, we show the interactions between MgRac1 and its effectors, including the PAK kinase Chm1 and NADPH oxidases (Nox1 and Nox2), by the yeast two-hybrid assay. While the Nox proteins are important for pathogenicity, the MgRac1-Chm1 interaction is responsible for conidiogenesis. A constitutively active chm1 mutant, in which the Rac1-binding PBD domain is removed, fully restores conidiation of the Mgrac1 deletion mutants, but these conidia do not develop appressoria normally and are not pathogenic to rice plants. Our data suggest that the MgRac1-Chm1 pathway is responsible for conidiogenesis, but additional pathways, including the Nox pathway, are necessary for appressorial formation and pathogenicity

Gross hematuria caused by a congenital intrarenal arteriovenous malformation: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the case of a woman who presented with gross hematuria and was treated with a percutaneous embolization.</p> <p>Case presentation</p> <p>A 48-year-old Caucasian woman presented with gross hematuria, left flank pain, and clot retention. The patient had no history of renal trauma, hypertension, urolithiasis, or recent medical intervention with percutaneous instrumentation. The patient did not report any bleeding disorder and was not taking any medication. Her systolic and diastolic blood pressure values were normal at presentation. The patient had anemia (8 mg/dL) and tachycardia (110 bpm). She underwent color and spectral Doppler sonography, multi-slice computed tomography, and angiography of the kidneys, which showed a renal arteriovenous malformation pole on top of the left kidney.</p> <p>Conclusions</p> <p>The feeding artery of the arteriovenous malformation was selectively embolized with a microcatheter introduced using a right transfemoral approach. By using this technique, we stopped the bleeding, preserved renal parenchymal function, and relieved the patient's symptoms. The hemodynamic effects associated with the abnormality were also corrected.</p

Regulation of pro-inflammatory and pro-fibrotic factors by CCN2/CTGF in H9c2 cardiomyocytes

Connective tissue growth factor (CTGF), also known as CCN2, is implicated in fibrosis through both extracellular matrix (ECM) induction and inhibition of ECM degradation. The role of CTGF in inflammation in cardiomyocytes is unknown. In some mesenchymal cell systems, CTGF mediates effects through TGF-β or tyrosine kinase cell surface receptor, TrkA, signalling. In this study, cellular mechanisms by which CTGF regulates pathways involved in fibrosis and inflammation were explored. Murine H9c2 cardiomyocytes were treated with recombinant human (rh)CTGF and ECM formation gene expression: fibronectin, collagen type -I and -III and ECM degradation genes: TIMP-1, TIMP-2 and PAI-1 were found to be induced. CTGF treatment also increased pro-inflammatory cytokines TNF-α, IL-6, MCP-1 and IL-8. CTGF upregulated TGF-β1 mRNA and rapidly induced phosphorylation of TrkA. The CTGF-induced pro-fibrotic and pro-inflammatory effects were blocked by anti-TGF-β neutralizing antibody and Alk 5 inhibitor (SB431542). A specific blocker of TrkA activation, k252a, also abrogated CTGF-induced effects on fibrosis and gene expresison of MCP-1 and IL-8, but not TNF-α or IL-6. Collectively, this data implicates CTGF in effects on pro-fibrotic genes and pro-inflammatory genes via TGF-β pathway signalling and partly through TrkA

CpG DNA modulates interleukin 1β-induced interleukin-8 expression in human bronchial epithelial (16HBE14o-) cells

BACKGROUND: Recognition of repeat unmethylated CpG motifs from bacterial DNA through Toll-like receptor (TLR-9) has been shown to induce interleukin (IL)-8 expression in immune cells. We sought to investigate the role of CpG oligodeoxynucleotides (ODN) on a human bronchial epithelial cells. METHODS: RT-PCR and Western blot analysis were used to determine expression of TLR-9 in human bronchial epithelial cells (16HBE14o-). Cells were treated with CpG ODN in the presence or absence of IL-1β and IL-8 protein was determined using ELISA. In some cases cells were pretreated with chloroquine, an inhibitor of TLR-9 signaling, or SB202190, an inhibitor of the mitogen activated protein kinase p38, prior to treatment with IL-1β and CpG. TLR9 siRNA was used to silence TLR9 prior to treatment with IL-1β and CpG. IκBα and p38 were assessed by Western blot, and EMSA's were performed to determine NF-κB activation. To investigate IL-8 mRNA stability, cells were treated with IL-1β in the absence or presence of CpG for 2 h and actinomycin D was added to induce transcriptional arrest. Cells were harvested at 15 min intervals and Northern blot analysis was performed. RESULTS: TLR-9 is expressed in 16HBE14o- cells. CpG synergistically increased IL-1β-induced IL-8 protein abundance, however treatment with CpG alone had no effect. CpC (a control ODN) had no effect on IL-1β-induced IL-8 levels. In addition, CpG synergistically upregulated TNFα-induced IL-8 expression. Silencing TLR9 using siRNA or pretreatment of cells with chloroquine had little effect on IL-1β-induced IL-8 levels, but abolished CpG-induced synergy. CpG ODN had no effect on NF-κB translocation or DNA binding in 16HBE14o- cells. Treatment with CpG increased phosphorylation of p38 and pretreatment with the p38 inhibitor SB202190 attenuated the synergistic increase in IL-8 protein levels. Analysis of the half-life of IL-8 mRNA revealed that IL-8 mRNA had a longer half-life following the co-treatment of CpG and IL-1β compared to treatment with IL-1β alone. CONCLUSION: Together, these data demonstrate that CpG modulates IL-8 synthesis in the presence of a pro-inflammatory mediator utilizing TLR9 and post-transcriptional mechanisms involving the activation of p38 and stabilization of IL-8 mRNA