162 research outputs found

    Effects of a Tailored Follow-Up Intervention on Health Behaviors, Beliefs, and Attitudes

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    Background: The high rates of relapse that tend to occur after short-term behavioral interventions indicate the need for maintenance programs that promote long-term adherence to new behavior patterns. Computer-tailored health messages that are mailed to participants or given in brief telephone calls offer an innovative and time-efficient alternative to ongoing face-to-face contact with healthcare providers. Methods: Following a 1-year behavior change program, 22 North Carolina health departments were randomly assigned to a follow-up intervention or control condition. Data were collected from 1999 to 2001 by telephone-administered surveys at preintervention and postintervention for 511 low-income, midlife adult women enrolled in the Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program at local North Carolina health departments. During the year after the behavior change program, intervention participants were mailed six sets of computer-tailored health messages and received two computer-tailored telephone counseling sessions. Main outcomes of dietary and physical activity behaviors, beliefs, and attitudes were measured. Results: Intervention participants were more likely to move forward into more advanced stages of physical activity change (p = 0.02); control participants were more likely to increase their level of dietary social support at follow-up (p = 0.05). Both groups maintained low levels of reported saturated fat and cholesterol intake at follow-up. No changes were seen in physical activity in either group. Conclusions: Mailed computer-tailored health messages and telephone counseling calls favorably modified forward physical activity stage movement but did not appreciably affect any other psychosocial or behavioral outcomes

    How to select a chiropractor for the management of athletic conditions

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    <p>Abstract</p> <p>Background</p> <p>Chiropractors are an integral part of the management of musculoskeletal injuries. A considerable communication gap between the chiropractic and medical professions exists. Subsequently referring allopathic practitioners lack confidence in picking a chiropractic practitioner with appropriate management strategies to adequately resolve sporting injuries. Subsequently, the question is often raised: "how do you find a good chiropractor?".</p> <p>Discussion</p> <p>Best practice guidelines are increasingly suggesting that musculoskeletal injuries should be managed with multimodal active and passive care strategies. Broadly speaking chiropractors may be subdivided into "modern multimodal" or "classical" (unimodal) in nature. The modern multimodal practitioner is better suited to managing sporting injuries by incorporating passive and active care management strategies to address three important phases of care in the continuum of injury from the acute inflammation/pain phase to the chronic/rehabilitation phase to the injury prevention phase. In contrast, the unimodal, manipulation only and typically spine only approach of the classical practitioner seems less suited to the challenges of the injured athlete. Identifying what part of the philosophical management spectrum a chiropractor falls is important as it is clearly not easily evident in most published material such as Yellow Pages advertisements.</p> <p>Summary</p> <p>Identifying a chiropractic practitioner who uses multimodal treatment of adequate duration, who incorporates active and passive components of therapy including exercise prescription whilst using medical terminology and diagnosis without mandatory x-rays or predetermined treatment schedules or prepaid contracts of care will likely result in selection of a chiropractor with the approach and philosophy suited to appropriately managing athletic conditions. Sporting organizations and associations should consider using similar criteria as a minimum standard to allow participation in health care team selections.</p

    Promoter Methylation in Head and Neck Squamous Cell Carcinoma Cell Lines Is Significantly Different than Methylation in Primary Tumors and Xenografts

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    Studies designed to identify novel methylation events related to cancer often employ cancer cell lines in the discovery phase of the experiments and have a relatively low rate of discovery of cancer-related methylation events. An alternative algorithm for discovery of novel methylation in cancer uses primary tumor-derived xenografts instead of cell lines as the primary source of nucleic acid for evaluation. We evaluated DNA extracted from primary head and neck squamous cell carcinomas (HNSCC), xenografts grown from these primary tumors in nude mice, HNSCC-derived cell lines, normal oral mucosal samples, and minimally transformed oral keratinocyte-derived cell lines using Illumina Infinum Humanmethylation 27 genome-wide methylation microarrays. We found >2,200 statistically significant methylation differences between cancer cell lines and primary tumors and when comparing normal oral mucosa to keratinocyte cell lines. We found no statistically significant promoter methylation differences between primary tumor xenografts and primary tumors. This study demonstrates that tumor-derived xenografts are highly accurate representations of promoter methylation in primary tumors and that cancer derived cell lines have significant drawbacks for discovery of promoter methylation alterations in primary tumors. These findings also support use of primary tumor xenografts for the study of methylation in cancer, drug discovery, and the development of personalized cancer treatments

    Common ADRB2 Haplotypes Derived from 26 Polymorphic Sites Direct β2-Adrenergic Receptor Expression and Regulation Phenotypes

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    The beta2-adrenergic receptor (beta2AR) is expressed on numerous cell-types including airway smooth muscle cells and cardiomyocytes. Drugs (agonists or antagonists) acting at these receptors for treatment of asthma, chronic obstructive pulmonary disease, and heart failure show substantial interindividual variability in response. The ADRB2 gene is polymorphic in noncoding and coding regions, but virtually all ADRB2 association studies have utilized the two common nonsynonymous coding SNPs, often reaching discrepant conclusions.We constructed the 8 common ADRB2 haplotypes derived from 26 polymorphisms in the promoter, 5'UTR, coding, and 3'UTR of the intronless ADRB2 gene. These were cloned into an expression construct lacking a vector-based promoter, so that beta2AR expression was driven by its promoter, and steady state expression could be modified by polymorphisms throughout ADRB2 within a haplotype. "Whole-gene" transfections were performed with COS-7 cells and revealed 4 haplotypes with increased cell surface beta2AR protein expression compared to the others. Agonist-promoted downregulation of beta2AR protein expression was also haplotype-dependent, and was found to be increased for 2 haplotypes. A phylogenetic tree of the haplotypes was derived and annotated by cellular phenotypes, revealing a pattern potentially driven by expression.Thus for obstructive lung disease, the initial bronchodilator response from intermittent administration of beta-agonist may be influenced by certain beta2AR haplotypes (expression phenotypes), while other haplotypes may influence tachyphylaxis during the response to chronic therapy (downregulation phenotypes). An ideal clinical outcome of high expression and less downregulation was found for two haplotypes. Haplotypes may also affect heart failure antagonist therapy, where beta2AR increase inotropy and are anti-apoptotic. The haplotype-specific expression and regulation phenotypes found in this transfection-based system suggest that the density of genetic information in the form of these haplotypes, or haplotype-clusters with similar phenotypes can potentially provide greater discrimination of phenotype in human disease and pharmacogenomic association studies

    A Prospective Three-Year Cohort Study of the Epidemiology and Virology of Acute Respiratory Infections of Children in Rural India

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    Acute respiratory infection (ARI) is a major killer of children in developing countries. Although the frequency of ARI is similar in both developed and developing countries, mortality due to ARI is 10-50 times higher in developing countries. Viruses are common causes of ARI among such children, yet the disease burden of these infections in rural communities is unknown.A prospective longitudinal study was carried out in children enrolled from two rural Indian villages at birth and followed weekly for the development of ARI, classified as upper respiratory infection, acute lower respiratory infection (ALRI), or severe ALRI. Respiratory syncytial virus (RSV), influenza, parainfluenza viruses and adenoviruses in nasopharyngeal aspirates were detected by direct fluorescent antibody testing (DFA) and, in addition, centrifugation enhanced culture for RSV was done. 281 infants enrolled in 39 months and followed until 42 months. During 440 child years of follow-up there were 1307 ARIs, including 236 ALRIs and 19 severe ALRIs. Virus specific incidence rates per 1000 child years for RSV were total ARI 234, ALRI 39, and severe ALRI 9; for influenza A total ARI 141, ALRI 39; for INF B total ARI 37; for PIV1 total ARI 23, for PIV2 total ARI 28, ALRI 5; for parainfluenza virus 3 total ARI 229, ALRI 48, and severe ALRI 5 and for adenovirus total ARI 18, ALRI 5. Repeat infections with RSV were seen in 18 children.RSV, influenza A and parainfluenza virus 3 were important causes of ARI among children in rural communities in India. These data will be useful for vaccine design, development and implementation purposes

    Representation and misrepresentation of scientific evidence in contemporary tobacco regulation:a review of tobacco industry submissions to the UK Government consultation on standardised packaging

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    BACKGROUND: Standardised packaging (SP) of tobacco products is an innovative tobacco control measure opposed by transnational tobacco companies (TTCs) whose responses to the UK government's public consultation on SP argued that evidence was inadequate to support implementing the measure. The government's initial decision, announced 11 months after the consultation closed, was to wait for 'more evidence', but four months later a second 'independent review' was launched. In view of the centrality of evidence to debates over SP and TTCs' history of denying harms and manufacturing uncertainty about scientific evidence, we analysed their submissions to examine how they used evidence to oppose SP. METHODS AND FINDINGS: We purposively selected and analysed two TTC submissions using a verification-oriented cross-documentary method to ascertain how published studies were used and interpretive analysis with a constructivist grounded theory approach to examine the conceptual significance of TTC critiques. The companies' overall argument was that the SP evidence base was seriously flawed and did not warrant the introduction of SP. However, this argument was underpinned by three complementary techniques that misrepresented the evidence base. First, published studies were repeatedly misquoted, distorting the main messages. Second, 'mimicked scientific critique' was used to undermine evidence; this form of critique insisted on methodological perfection, rejected methodological pluralism, adopted a litigation (not scientific) model, and was not rigorous. Third, TTCs engaged in 'evidential landscaping', promoting a parallel evidence base to deflect attention from SP and excluding company-held evidence relevant to SP. The study's sample was limited to sub-sections of two out of four submissions, but leaked industry documents suggest at least one other company used a similar approach. CONCLUSIONS: The TTCs' claim that SP will not lead to public health benefits is largely without foundation. The tools of Better Regulation, particularly stakeholder consultation, provide an opportunity for highly resourced corporations to slow, weaken, or prevent public health policies

    HIV Prevention in High-Risk Women in South Africa: Condom Use and the Need for Change

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    INTRODUCTION: Young women are at disproportionate risk of HIV infection in South Africa. Understanding risk behaviors and factors associated with ability to negotiate safe sex and condom use is likely to be key in curbing the spread of HIV. Traditionally prevention efforts have focused on creating behavioral changes by increasing knowledge about HIV/AIDS. METHODS: This was a cross-sectional analysis from a prospective observational cohort study of 245 women at a high-risk of HIV infection in KwaZulu-Natal, South Africa. RESULTS: Participants demonstrated a high level of HIV/AIDS knowledge. Overall, 60.3% of participants reported condom use. Reported condom use at last sexual encounter varied slightly by partner type (57.0% with steady versus 64.4% with casual partners), and self-perceived ability to choose to use a condom was significantly lower with steady partners compared to casual partners (p<0.01). In multivariate analysis, women who had high school education were more likely to use condoms at their last sex encounter compared to those with only primary school education (RR of 1.36 (95% Confidence Interval (CI) 1.06-1.75) and 1.46 (95% CI 1.13-1.88) for grades 8-10 and 11-12, respectively). Those who used condoms as a contraceptive method were twice as likely to use condoms compared to women who did not report using them as a contraceptive method. Greater perceived ability to choose to use condoms was associated with higher self-reported condom use at last encounter, irrespective of partner type (RR = 2.65 (95% CI 2.15-32.5). DISCUSSION: Self-perceived ability to use condoms, level of formal education and condom use as a contraceptive were all significantly associated with self-reported condom use at last sexual encounter. These findings suggest that that gender inequality and access to formal education, as opposed to lack of HIV/AIDS knowledge, prevent safer sexual practices in South Africa

    Primary Coenzyme Q Deficiency in Pdss2 Mutant Mice Causes Isolated Renal Disease

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    Coenzyme Q (CoQ) is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment

    Alternative HER/PTEN/Akt Pathway Activation in HPV Positive and Negative Penile Carcinomas

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    Copyright: 2011 Stankiewicz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood, though risk factors include human papillomavirus (HPV). Disruption of HER/PTEN/Akt pathway is present in many cancers; however there is little information on its function in PSCC. We investigated HER family receptors and phosphatase and tension homolog (PTEN) in HPV-positive and negative PSCC and its impact on Akt activation using immunohistochemistry and fluorescent in situ hybridisation (FISH). Methodology/Principal Findings: 148 PSCCs were microarrayed and immunostained for phosphorylated EGFR (pEGFR), HER2, HER3, HER4, phosphorylated Akt (pAkt), Akt1 and PTEN proteins. EGFR and PTEN gene status were also evaluated using FISH. HPV presence was assessed by PCR. pEGFR expression was detected significantly less frequently in HPV-positive than HPV-negative tumours (p = 0.0143). Conversely, HER3 expression was significantly more common in HPV-positive cases (p = 0.0128). HER4, pAkt, Akt and PTEN protein expression were not related to HPV. HER3 (p = 0.0054) and HER4 (p = 0.0002) receptors significantly correlated with cytoplasmic Akt1 immunostaining. All three proteins positively correlated with tumour grade (HER3, p = 0.0029; HER4, p = 0.0118; Akt1, p = 0.0001). pEGFR expression correlated with pAkt but not with tumour grade or stage. There was no EGFR gene amplification. HER2 was not detected. PTEN protein expression was reduced or absent in 62% of tumours but PTEN gene copy loss was present only in 4% of PSCCs. Conclusions/Significance: EGFR, HER3 and HER4 but not HER2 are associated with penile carcinogenesis. HPV-negative tumours tend to express significantly more pEGFR than HPV-positive cancers and this expression correlates with pAkt protein, indicating EGFR as an upstream regulator of Akt signalling in PSCC. Conversely, HER3 expression is significantly more common in HPV-positive cases and positively correlates with cytoplasmic Akt1 expression. HER4 and PTEN protein expression are not related to HPV infection. Our results suggest that PSCC patients could benefit from therapies developed to target HER receptors.Peer reviewedFinal Published versio

    The gastrointestinal nematode Trichostrongylus colubriformis down-regulates immune gene expression in migratory cells in afferent lymph

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    Background: Gastrointestinal nematode (GIN) infections are the predominant cause of economic losses in sheep. Infections are controlled almost exclusively by the use of anthelmintics which has lead to the selection of drug resistant nematode strains. An alternative control approach would be the induction of protective immunity to these parasites. This study exploits an ovine microarray biased towards immune genes, an artificially induced immunity model and the use of pseudo-afferent lymphatic cannulation to sample immune cells draining from the intestine, to investigate possible mechanisms involved in the development of immunity.\ud \ud Results: During the development of immunity to, and a subsequent challenge infection with Trichostrongylus colubriformis, the transcript levels of 2603 genes of cells trafficking in afferent intestinal lymph were significantly modulated (P < 0.05). Of these, 188 genes were modulated more than 1.3-fold and involved in immune function. Overall, there was a clear trend for down-regulation of many genes involved in immune functions including antigen presentation, caveolar-mediated endocytosis and protein ubiquitination. The transcript levels of TNF receptor associated factor 5 (TRAF5), hemopexin (HPX), cysteine dioxygenase (CDO1), the major histocompatability complex Class II protein (HLA-DMA), interleukin-18 binding protein (IL-18BP), ephrin A1 (EFNA1) and selenoprotein S (SELS) were modulated to the greatest degree.\ud \ud Conclusions: This report describes gene expression profiles of afferent lymph cells in sheep developing immunity to nematode infection. Results presented show a global down-regulation of the expression of immune genes which may be reflective of the natural temporal response to nematode infections in livestock
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