269 research outputs found

    Cybergriping: Violating the Law while E-Complaining

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    The emergence of Web communications has given rise to complaint sites which serve as central forums for both consumers and employees to share their bad experiences. These complaint sites provide for cybergriping in various forms. This paper explores the concept of cybergriping and its relevance to the hospitality and tourism industry from employee and customer perspectives. Court cases in which cybergriping played a key role are reviewed, and recommendations are offered on how hospitality and tourism businesses can address the problem of cybergriping

    Short Palate, Lung, and Nasal Epithelial Clone 1 Has Antimicrobial and Antibiofilm Activities against the Burkholderia cepacia Complex

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    ABSTRACT The opportunistic bacteria of the Burkholderia cepacia complex (Bcc) are extremely pathogenic to cystic fibrosis (CF) patients, and acquisition of Bcc bacteria is associated with a significant increase in mortality. Treatment of Bcc infections is difficult because the bacteria are multidrug resistant and able to survive in biofilms. Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) is an innate defense protein that is secreted by the upper airways and pharynx. While SPLUNC1 is known to have antimicrobial functions, its effects on Bcc strains are unclear. We therefore tested the hypothesis that SPLUNC1 is able to impair Bcc growth and biofilm formation. We found that SPLUNC1 exerted bacteriostatic effects against several Bcc clinical isolates, including B. cenocepacia strain J2315 (50% inhibitory concentration [IC 50 ] = 0.28 μM), and reduced biofilm formation and attachment (IC 50 = 0.11 μM). We then determined which domains of SPLUNC1 are responsible for its antimicrobial activity. Deletions of SPLUNC1's N terminus and α6 helix did not affect its function. However, deletion of the α4 helix attenuated antimicrobial activity, while the corresponding α4 peptide displayed antimicrobial activity. Chronic neutrophilia is a hallmark of CF lung disease, and neutrophil elastase (NE) cleaves SPLUNC1. However, we found that the ability of SPLUNC1 to disrupt biofilm formation was significantly potentiated by NE pretreatment. While the impact of CF on SPLUNC1-Bcc interactions is not currently known, our data suggest that understanding this interaction may have important implications for CF lung disease

    Relation of cardiovascular risk factors in women approaching menopause to menstrual cycle characteristics and reproductive hormones in the follicular and luteal phases

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    CONTEXT: Menstrual cycle characteristics may be associated with cardiovascular disease (CVD) risk. OBJECTIVE: The objective of this study was to describe the relationships between menstrual cycle characteristics and daily reproductive hormone measures with CVD risk factors in middle-aged women. DESIGN AND SETTING: Cross-sectional associations were examined between CVD risk factors and urinary LH, FSH, estrone conjugates, and pregnanediol glucuronide (Pdg) measured across one menstrual cycle or 50 d. PARTICIPANTS: Menstruating women (n = 500) who were free from diabetes or past stroke or heart attack enrolled in the Daily Hormone Study-Study of Women\u27s Health across the Nation were studied. MAIN OUTCOME MEASURES: Body mass index (BMI), blood pressure, hemostatic, and metabolic factors were measured. RESULTS: Few differences existed in risk factors between women with evidence of luteal activity and those with no evidence of luteal activity. Associations between elevated CVD risk factors and long cycle length were reduced substantially by age and BMI adjustments. Those with lower estrone conjugate and PdG averaged across the follicular phase had higher waist circumference, triglycerides, insulin, plasminogen activator inhibitor type-1, tissue type plasminogen activator-antigen, and factor VIIc levels in age- and BMI-adjusted analyses (P \u3c 0.05). CONCLUSIONS: In midlife menstruating women, a longer cycle length was related to CVD risk factors, in large part through their common association with BMI. More favorable levels of metabolic and hemostatic factors were associated with higher levels of follicular-phase estrogen, a pattern consistent with a more competent ovary, and higher levels of follicular-phase PdG, perhaps of adrenal origin. Metabolic and hemostatic factors may be sensitive to hormonal variation during the early perimenopausal transition

    Primary care consultation patterns prior to suicide: a nationally representative case-control study.

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    Consultation with primary health care may provide an opportunity to identify patients at higher suicide risk. To explore primary care consultation patterns in the 5 years before suicide to identify suicide high-risk groups and common reasons for consulting. A case-control study in England from 2001 to 2019 using electronic health records. Analysis of 14515 patients aged ≥15 who died by suicide and up to 40 matched live controls per case (N=594674). Frequent consultations (>once per month in the final year) were associated with increased suicide risk (age and sex adjusted odds ratio (OR) 5.88; 95% CI: 5.47-6.32). The associated rise in suicide risk was seen across all sociodemographic groups as well as in those with and without psychiatric comorbidities. However, specific groups were more influenced by the effect of high-frequency consultation (>once per month in the final year) demonstrating higher suicide risk compared to their counterparts who consulted once: females (adjusted OR 9.50; 95% CI: 7.82-11.54); patients aged 15 to 45 (adjusted OR 8.08; 95% CI: 7.29-8.96); patients experiencing less socioeconomic deprivation (adjusted OR 6.56; 95% CI: 5.77-7.46); and those with psychiatric conditions (adjusted OR 4.57;95% CI: 4.12 to 5.06). Medication review, depression and pain were the commonest reasons for which suicide decedents consulted in the year before death. Escalating, or more than monthly consultations are associated with increased suicide risk regardless of patients' sociodemographic characteristics and regardless of the presence (or absence) of known psychiatric illnesses

    Structural Features Essential to the Antimicrobial Functions of Human SPLUNC1

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    SPLUNC1 is an abundantly secreted innate immune protein in the mammalian respiratory tract that exerts bacteriostatic and antibiofilm effects, binds to lipopolysaccharide (LPS), and acts as a fluid-spreading surfactant. Here, we unravel the structural elements essential for the surfactant and antimicrobial functions of human SPLUNC1 (short palate lung nasal epithelial clone 1). A unique α-helix (α4) that extends from the body of SPLUNC1 is required for the bacteriostatic, surfactant, and LPS binding activities of this protein. Indeed, we find that mutation of just four leucine residues within this helical motif to alanine is sufficient to significantly inhibit the fluid spreading abilities of SPLUNC1, as well as its bacteriostatic actions against Gram-negative pathogens Burkholderia cenocepacia and Pseudomonas aeruginosa. Conformational flexibility in the body of SPLUNC1 is also involved in the bacteriostatic, surfactant, and LPS binding functions of the protein as revealed by disulfide mutants introduced into SPLUNC1. In addition, SPLUNC1 exerts antibiofilm effects against Gram-negative bacteria, although α4 is not involved in this activity. Interestingly, though, the introduction of surface electrostatic mutations away from α4 based on the unique dolphin SPLUNC1 sequence, and confirmed by crystal structure, is shown to impart antibiofilm activity against Staphylococcus aureus, the first SPLUNC1-dependent effect against a Gram-positive bacterium reported to date. Together, these data pinpoint SPLUNC1 structural motifs required for the antimicrobial and surfactant actions of this protective human protein

    No Evidence for XMRV Nucleic Acids, Infectious Virus or Anti-XMRV Antibodies in Canadian Patients with Chronic Fatigue Syndrome

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    The gammaretroviruses xenotropic murine leukemia virus (MLV)-related virus (XMRV) and MLV have been reported to be more prevalent in plasma and peripheral blood mononuclear cells of chronic fatigue syndrome (CFS) patients than in healthy controls. Here, we report the complex analysis of whole blood and plasma samples from 58 CFS patients and 57 controls from Canada for the presence of XMRV/MLV nucleic acids, infectious virus, and XMRV/MLV-specific antibodies. Multiple techniques were employed, including nested and qRT-PCR, cell culture, and immunoblotting. We found no evidence of XMRV or MLV in humans and conclude that CFS is not associated with these gammaretroviruses

    Addressing Arctic Challenges Requires a Synoptic Ocean Survey

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    A coordinated effort involving trailblazing science — and icebreaking ships — from many nations is needed to fill gaps in our understanding of the Arctic Ocean and how it’s changing

    Coordination by Cdc42 of actin, contractility, and adhesion for melanoblast movement in mouse skin

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    YesThe individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large, bulky pseudopods with dynamic actin bursts. Despite assuming an elongated shape usually associated with fast mesenchymal motility, Cdc42 knockout melanoblasts migrated slowly and inefficiently in the epidermis, with nearly static pseudopods. Although much of the basic actin machinery was intact, Cdc42 null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics.Cancer Research UK (to L.M.M. [A17196], R.H.I. [A19257], and S.W.G.T.) and NIH grants P01-GM103723 and P41-EB002025 (to K.M.H.). N.R.P. is supported by a Pancreatic Cancer Research Fund grant (to L.M.M.). Funding to Prof. Rottner by the Deutsche Forschungsgemeinschaft (grant RO2414/3-2)

    Association of maternal circulating 25(OH)D and calcium with birth weight: A mendelian randomisation analysis

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    Systematic reviews of randomised controlled trials (RCTs) have suggested that maternal vitamin D (25[OH]D) and calcium supplementation increase birth weight. However, limitations of many trials were highlighted in the reviews. Our aim was to combine genetic and RCT data to estimate causal effects of these two maternal traits on offspring birth weight
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